A Phase II Study of Sodium Cridanimod in Conjunction With Progestin Therapy in Patients With Progesterone Receptor Negative Recurrent or Persistent Endometrial Carcinoma
This is an open label, multi-center, single arm phase II study. The study will investigate
the efficacy of sodium cridanimod in conjunction with progestin therapy in a population of
patients with recurrent or persistent PrR-negative endometrial cancer.
Eligible patients will be enrolled into the study and administered sodium cridanimod in
combination progestin therapy. Objective responses will be assessed at 12 week intervals.
Patients will be treated for a 12 month period, followed by an additional 12 month follow up
period or to disease progression whichever occurs first.
Important objectives of the study are to investigate the effect of sodium cridanimod in
conjunction with progestin therapy on the level of PrR in tumor tissue and how this
correlates to efficacy. To accomplish this objective, some of the patients enrolled in the
study will undergo two tumor biopsies that will allow measurement of PrR levels in the tumor
tissue before the treatment and after 4 weeks of therapy.
A Randomized, Open-Label Study Comparing the Combination of YONDELIS and DOXIL/CAELYX With DOXIL/CAELYX Monotherapy for the Treatment of Advanced-Relapsed Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancer
This is a randomized (individuals assigned to study treatment by chance), open-label
(identity of assigned study drug will be known), active-controlled study in adult female
patients with platinum-sensitive advanced-relapsed epithelial ovarian, primary peritoneal,
or fallopian tube cancer who received 2 previous lines of platinum-based chemotherapy.
Approximately 670 participants will be enrolled. Patients will be stratified by 4 criteria
defined in the protocol and randomly assigned in a 1:1 ratio to the trabectedin+DOXIL
combination therapy group (Arm A) or to the DOXIL (pegylated liposomal doxorubicin)
monotherapy group (Arm B). During the treatment phase, patients will receive study drug
infusions according to 21-day cycles in Arm A and 28-day cycles in Arm B. Treatment will
continue until the occurrence of disease progression or unacceptable treatment toxicity, or
until 2 cycles beyond a confirmed complete response is documented. Up to 2 additional cycles
of study drug are allowed after complete response, at the discretion of the principal
investigator. Efficacy assessments will be evaluated using Response Evaluation Criteria in
Solid Tumors. Disease assessments, including assessments for patients who discontinue
treatment for reasons other than disease progression, will be performed until disease
progression, the start of subsequent anticancer therapy, withdrawal of consent, or the
clinical cutoff date. Collection of survival status will continue until at least 514 deaths
have been observed. Serial pharmacokinetic (PK) samples will be collected in a subset of
patients who voluntarily consent to the PK portion of the study. Safety will be monitored
throughout the study. An interim analysis of overall survival (OS) will be performed after
approximately 308 participants have died. The final analysis of OS will occur when
approximately 514 deaths have been observed.
RTOG-1203 A Randomized Phase III Study of Standard Vs. IMRTt Pelvic Radiation for Post-Operative Treatment of Endometrial and Cervical Cancer (TIME-C)
- To determine if pelvic intensity-modulated radiation therapy (IMRT) reduces acute
gastrointestinal toxicity in the 5th week (after 23-25 fractions) of pelvic radiation as
measured with the expanded prostate cancer index composite (EPIC) instrument.
- To determine if grade 2+ gastrointestinal toxicity (Common Terminology Criteria for
Adverse Events version 4.0 [CTCAE v. 4.0]) is reduced with IMRT compared to conventional
whole-pelvis radiation therapy (WPRT).
- To determine if grade 2+ hematologic toxicity (CTCAE v. 4.0) is reduced with IMRT
compared to conventional WPRT.
- To determine if urinary toxicity is reduced with IMRT using the EPIC urinary domain.
- To validate EPIC bowel and urinary domains in women undergoing either IMRT pelvic
radiation treatment or four-field pelvic radiation treatment for endometrial or cervical
- To assess the impact of pelvic IMRT on quality of life using the Functional Assessment
of Cancer Therapy-General (FACT-G) with cervix subscale.
- To determine if there is any difference in local-regional control, disease-free
survival, and overall survival between patients treated with IMRT as compared to
- To perform a health-utilities analysis to measure the financial impact of pelvic IMRT
via the EQ-5D instrument.
- To identify molecular predictors of radiation toxicity and novel circulating cancer
OUTLINE: This is a multicenter study. Patients are stratified according to type of cancer
(endometrial vs cervical), chemotherapy (none vs 5 courses of weekly cisplatin at 40 mg/m²),
and radiation dose (45 Gy vs 50.4 Gy). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients undergo standard (3-dimensional) radiation therapy 5 days a week for up
to 5-6 weeks.
- Arm II: Patients undergo intensity-modulated radiation therapy (IMRT) 5 days a week for
up to 5-6 weeks.
Some patients receive cisplatin IV over 1 hour on day 1. Treatment continues weekly for 5
weeks, concurrently with radiation therapy, in the absence of unacceptable toxicity or
Tissue and blood samples may be collected for biomarker and correlative analysis.
Quality of life may be assessed by questionnaires (including the Expanded Prostate Cancer
Index Composite [EPIC], the Functional Assessment of Cancer Therapy-General [FACT-G, Version
4], the EQ-5D, and the Common Toxicity Criteria Adverse Events - Patient-Reported Outcome
[PRO-CTCAE]) instruments at baseline and periodically during and after study therapy.
After completion of study therapy, patients are followed every 6 months for the first 2 years
and then annually for 5 years.
Active, not recruiting | Gynecologic Cancers | Multisite
GOG 0263: RANDOMIZED PHASE III CLINICAL TRIAL OF ADJUVANT RADIATION VERSUS CHEMORADIATION IN INTERMEDIATE RISK, STAGE I/IIA CERVICAL CANCER TREATED WITH INITIAL RADICAL HYSTERECTOMY AND PELVIC LYMPHADENECTOMY
I. To determine if post-operative adjuvant chemo-radiation therapy (CRT) can significantly
improve recurrence-free survival (RFS) when compared to radiation therapy (RT) alone in stage
I-IIA cervical cancer patients with intermediate-risk factors after treatment with radical
I. To determine whether post-operative adjuvant CRT can improve overall survival (OS) when
compared to RT alone in stage I-IIA cervical cancer patients with intermediate risk factors
after treatment with radical hysterectomy.
II. To assess differences (across treatment arms) in incidence and severity of
therapy-attributed adverse events utilizing the active version of Common Terminology Criteria
for Adverse Events (CTCAE).
III. To provide assessment of patient risk vs benefit (positive study only). IV. To determine
whether post-operative adjuvant CRT improves the health-related quality-of-life (QOL)
(compared to RT alone) as measured by Functional Assessment of Cancer Therapy-Cervix
(FACT-Cx) Trial Outcome Index (TOI) and produce favorable toxicity profiles (with particular
focus on treatment related genitourinary, gastrointestinal, neurological, pain and sexual
I. To bank archival tumor tissue for research studies, including studies that evaluate the
association between biomarkers, RFS, OS, and clinical-surgical-pathologic characteristics in
patients randomized to post-operative adjuvant CRT compared to RT alone.
II. To bank deoxyribonucleic acid (DNA) from whole blood for research studies, including
studies that evaluate associations between single nucleotide polymorphisms (SNPs), and
measures of clinical outcome, including RFS, OS, and adverse events in patients randomized to
post-operative adjuvant CRT compared to RT alone.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients undergo pelvic external-beam radiation therapy (EBRT) or intensity-modulated
radiation therapy (IMRT) 5 days a week for 5.5 weeks.
ARM II: Patients receive cisplatin IV over 1-2 hours on day 1 and undergo radiotherapy as in
Arm I. Treatment with cisplatin repeats every 7 days for up to 6 courses in the absence of
disease progression or unacceptable toxicity.
After completion of study therapy, patients are followed up every 3 months for 2 years, every
6 months for 3 years, and then annually thereafter.
0S-11-4 PhII-118 ABT-888 Phase II Randomized Trial of the Combination of ABT-888 With Metronomic Oral Cyclophosphamide in Refractory BRCA-Positive Ovarian, Primary Peritoneal or Ovarian High-Grade Serous Carcinoma, Fallopian Tube Cancer, Triple-Negative Breast Cancer, and Low-Grade Non-Hodgkins Lymphoma
- The poly (ADP-ribose) polymerase (PARP) family of enzymes is critical for maintaining
genomic stability by regulating a variety of DNA repair mechanisms.
- Individuals with deleterious mutations in the BRCA1 or BRCA2 tumor suppressor genes have
an increased risk of developing breast and ovarian cancers due to impaired or defective
DNA damage repair; these individuals have an increased susceptibility to DNA-damaging
agents and PARP inhibitors. Inhibition of PARP inhibits the repair of DNA damage caused
by alkylating agents such as cyclophosphamide.
- Metronomic cyclophosphamide has demonstrated efficacy in several tumor types. The PARP
inhibitor ABT-888 has been shown to potentiate the action of cyclophosphamide in
xenograft models. This combination is well tolerated in a Phase I study and showing
- Compare the response rate (complete response (CR) + partial response (PR)) of the
combination of ABT-888 with metronomic oral cyclophosphamide to the response rate
(CR+PR) of metronomic oral cyclophosphamide in patients with deleterious BRCA mutations
and refractory ovarian cancer or patients with primary peritoneal or ovarian high-grade
serous carcinoma or fallopian tube cancer.
- Compare the response rate (CR+PR) of the combination of ABT-888 with metronomic oral
cyclophosphamide to the response rate (CR+PR) of single-agent oral cyclophosphamide in
patients with triple-negative metastatic breast cancer, stratified for deleterious BRCA
- Compare the response rate (CR+PR) of the combination of ABT-888 with metronomic oral
cyclophosphamide to the response rate (CR+PR) of single-agent metronomic oral
cyclophosphamide in patients with refractory low-grade lymphomas.
- Determine PAR levels in tumor biopsies, evaluate in archival tissue whether patients tumors
have mutations in genes involved in DNA damage repair (e.g., BRCA/Fanconi anemia/protein 53
(p53)), perform exploratory gene expression profiling to correlate PARP messenger ribonucleic
acid (mRNA) levels or BRCA mutation status with response to therapy, count circulating tumor
cells (CTCs), and determine H2AX levels in CTCs and tumor biopsies (National Cancer Institute
(NCI) clinical center only).
-Adults with refractory BRCA-positive ovarian cancer, primary peritoneal or ovarian
high-grade serous carcinoma, fallopian tube cancer, triple-negative breast cancer, or
low-grade lymphoid malignancies (non-Hodgkin's lymphoma) whose disease has progressed
following at least one line of therapy.
- This is a randomized, multi-histology Phase II trial with patients enrolled into 3
cohorts: BRCA-positive ovarian cancer or primary peritoneal or ovarian high-grade serous
carcinoma or fallopian tube cancer (A); triple-negative breast cancer (B); or low grade
non-Hodgkin's lymphoma (C). Patients in cohort A will be randomized to the combination
of ABT-888 with metronomic oral cyclophosphamide or metronomic oral cyclophosphamide
alone. Patients in cohort B will be randomized to the combination of ABT-888 with
metronomic oral cyclophosphamide or metronomic oral cyclophosphamide alone. Patients in
cohort C will be randomized to the combination of ABT-888 with metronomic oral
cyclophosphamide or metronomic oral cyclophosphamide alone.
- Cyclophosphamide (50 mg) and ABT-888 (60 mg) will be administered orally once a day,
continuously in 21-day cycles.
3R-12-2 Phase II Trial Of Neoadjuvant Bevacizumab With Modified FOLFOX7 In Patients With Stage II And III Rectal Cancer
There were about 40,000 cases of rectal cancer in the United States in 2011. The standard treatment is surgery, but the cancer recurs in 10-20% of cases. To decrease recurrence, chemotherapy and radiation are given before surgery. However, radiation with chemotherapy has not been shown to improve overall survival, so chemotherapy is also given for 3-4 months after surgery. Radiation is also associated with short and long term side effects and has differing effects on survival depending on the stage of disease, but the degree of tumor response after radiation with chemotherapy is associated with survival. Thus, tumor response or complete pathologic response (CPR) appears to be a good indicator for long term outcomes. A previous study has shown that chemotherapy without radiation using FOLFOX (Oxaliplatin, Leukovorin and Fluororacil) and Bevacizumab yields a CPR rate of 27% and does not compromise the removal of the tumor with surgery. This Phase II study will attempt to validate the results of that study using FOLFOX and Bevacizumab without radiation in patients with rectal cancer that has not spread and can be removed surgically. This study will also assess the rate that the tumor recurs and assess specific biomarkers that may be associated with tumor response.Once participants sign the informed consent and are deemed eligible for the study, participants will receive a modified FOLFOX regimen, called mFOLFOX7, with Bevacizumab through a vein in the arm every 2 weeks. Every 2 weeks is called a cycle. During the study, participants will have the following procedures done during each cycle: a physical exam, vital signs, blood tests, performance status, assessment of side effects, review of medications, and tumor assessments with ultrasound and radiographic scans at the end of study treatment before surgery. All participants will stop taking study drug(s) if their disease worsens, they will not have surgery, they have another illness which prevents them from taking the study drug(s), they cannot tolerate the side effects, they withdraw from the study, or their study doctor thinks that being on the study is no longer in their best interest. All participants will be followed every 3 months after stopping the study drug(s) for the first 2 years, and then every 6 months for 3 years.The primary endpoint of this study is complete pathologic response. A two-stage Simon design was used to calculate sample size. All subjects will be analyzed as intent to treat. Biomarkers will be analyzed using a contingency table, bar plots, Fisher's exact test, scatterplots, and two-sample Wilcoxon or t-test. An optimal cut-off value of the continuous biomarker will be chosen to separate patients into 2 groups in term of probability of CPR using the maximal chi-square approach. P value for the associations will be adjusted using bootstrap like simulations.
Recruiting | Colon / Rectal Cancer | Not Multisite
0C-14-10: A Phase I, Open-Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumour Activity of Ascending Doses of AZD5363 under Adaptable Dosing Schedules in Patients with Advanced Solid Malignancies
This is a phase I, open-label, multicentre study of AZD5363 administered orally in participants with advanced solid malignancies. AZD5363 is a novel, potent, selective inhibitor of the kinase activity of AKT (also known as protein kinase B). AZD5363 acts on cancers by blocking signalling through the AKT cellular survival pathway, leading to inhibition of cell proliferation and increased cell death. There are 6 parts to this study. USC will only take part in parts C, D, E and F. Parts C, D, E and F will investigate the tolerability and initial signs of anti-tumour activity of AZD5363 in tumour types that are considered most likely to be sensitive to AKT inhibition, as a result of bearing a mutation of PIK3CA, AKT1, PTEN or other molecular aberrations leading to dysregulation of the PI3K/AKT pathway. Part C will focus on tumours with a mutation of PIK3CA and will contain three separate cohorts Part D will focus on tumours with mutations of AKT1 or other molecular aberrations leading to dysregulation of the PI3K/AKT pathway, and will contain three separate cohorts Part E will focus on patients with advanced or metastatic ER positive breast tumours with mutations of AKT1 and will contain two separate cohorts. Part F will focus on patients with advanced or metastatic ER positive breast tumours with alterations of PTEN (restricted to genomic alterations which are predicted to ablate function of the gene, e.g. alterations with known functional significance and/or of most likely therapeutic significance. Each participant will receive AZD5363 as an intermittent regimen of 480 mg twice daily for 4 days on, 3 days off dosing Primary objective for Part C is to investigate the safety and tolerability of AZD5363 in participants with advanced or metastatic estrogen receptor positive (ER+) or human epidermal growth factor receptor 2 positive (HER2+) breast cancer, gynaecological (ovarian, cervical or endometrial) cancer, or other advanced solid cancer that has a PIK3CA mutation. Primary objective for Part D is to investigate the safety and tolerability of AZD5363 in patients with advanced or metastatic ER+ or HER2+ breast cancer, gynaecological (ovarian, cervical or endometrial) or other advanced solid cancer that has an AKT1 mutation or other molecular aberration leading to dysregulation of the PI3K/AKT pathway Primary objective for Part E is to investigate the safety and tolerability of AZD5363 in combination with fulvestrant in patients with advanced or metastatic ER positive breast cancer that has an AKT1 mutation. Primary objective for Part F is to investigate the safety and tolerability of AZD5363 in combination with fulvestrant in patients with advanced or metastatic ER+ positive breast cancer that has a PTEN mutation. Primary study endpoints for Parts C, D, E and F will be safety and tolerability.
GOG-9929 A Phase I Trial of Sequential Ipilimumab After Chemoradiation for the Primary Treatment of Patients with Locally Advanced Cervical Cancer Stages IB2/IIA with Positive Para-Aortic Lymph Nodes Only and Stage IIB/IIIB/IVA with Positive Lymp Nodes
Background:Historically, the treatment of invasive cervical cancer was limited to either surgery or radiotherapy. The addition of systemic chemotherapy to radiation therapy for the treatment of cervical cancer has revolutionized the management and clinical outcome of these patients. The discovery of tumor-associated antigens (TAAs) on tumors and host immune responses to these antigens has been heralded as a promising targeted immunotherapeutic strategy. Ipilimumab affects tumor cells indirectly, and measurable clinical effects emerge after the immunological effects.Objectives:To estimate the maximum tolerated dose (MTD) and dose-limiting toxicities(DLT) of adjuvant ipilimumab following concurrent weekly cisplatin and extended field radiation in women with newly diagnosed locally advanced cervical cancer Stage IB2/ IIA with-positive para-aortic lymph nodes only and Stage IIB/ IIIB/ IVA with positive lymph nodes. To examine progression free survival for 1 year after study completion.Primary Endpoints: DLTs occurring in the first two cycles of adjuvant ipilimumab (as defined in Section 5.3) in the dose escalation phaseDLTs occurring in the four cycles of adjuvant ipilimumab in the feasibility phaseToxicities as assessed by CTCAE Version 4Description of Study Arms:Concurrent Weekly Cisplatin 40mg/m2/week (max dose 70 mg) and Extended Field Radiation: pelvis + para-aortics4500 cGy in 25 fractions to the para-aortic nodes (180 cGy/fraction)4500 cGy in 25 fractions to the pelvis (180 cGy/fraction)Intracavitary BrachytherapyLDR 4000cGy OR HDR 3000cGyAdjuvant Immunotherapy: Dose Escalation SchemaDose Level Ipilimumab Rx Schedule1 (Starting Dose) 3 mg/kg q3 weeks x 4*2 10 mg/kg q3 weeks x 4*1a 6 mg/kg q3 weeks x 4*Follow-up:Participants will be followed every 3 months for 1 more year.Statistics/Analysis:Patient entry will be accomplished via the GOG Statistical and Data Centers Phase I reservation and registration systems. This study will evaluate the MTD and feasibility of the study regimens by assessing the tolerability through dose limiting toxicities.
Active, not recruiting | Gynecologic Cancers | Multisite
5U-13-1 PhII-129, NCI 9322 A Phase 2 Study of XL184 (Cabozantinib) in Recurrent or Metastatic Endometrial Cancer
Endometrial cancer is the fourth most common cancer diagnosis in North American women. Factors such as age greater than 60, depth of tumor invasion, and involvement of the lower uterus have shown importance in identifying those at a particularly high risk of failing primary therapy. Women whose disease has spread, together with those with more advanced disease at initial presentation have a poor outcome. In contrast with the high 5-year disease free survival in early stage disease, women with disease that has spread can expect about a 20% chance of 5-year disease free survival. Given the diversity existing in this patient population regarding both clinical treatment and treatment response, novel approaches are needed targeting molecular subgroups of this disease that will improve outcomes for patients with endometrial cancer. This is a single arm phase II study to evaluate the activity of the multi-targeted inhibitor cabozantinib in endometrial cancer. Cabozantinib targets receptors that are important for tumor growth, spread, and vessel formation. Patients enrolled for this study will have laboratory confirmed endometrial cancer with documented disease worsening after one line of chemotherapy for disease that has spread or with disease worsening within 12 months of completing chemotherapy after surgery. Chemotherapy and radiation given after surgery will be allowed as well as prior hormonal therapy. In addition, a separate cohort of patients with unusual histology endometrial cancer (including clear cell, carcinosarcoma) will also be enrolled. Dosing of cabozantinib will be continuous (7 days a week) on a 28 day cycle, with response evaluation performed every 2 cycles with CT tumour measurements. The study has a dual primary endpoint of improved response rate and a 12-week progression-free-survival (PFS).The statistical plan to assess effectiveness will only apply to the experimental cohort (serous and endometroid histology patients). Statistical plan is based on effectiveness in serous, endometroid and mixed histology endometrial cancer. A modified Simon two-stage design is planned with a maximum accrual of 36 patients to discriminate between co-primary endpoints of tumor response rates of 30% vs. 10% and 12-week progression-free-survival (PFS) rates of 55% vs. 30% (corresponding to median PFS of 3.4 vs. 1.7 months). Stage I has a planned accrual of 18 patients. If no more than 2 objective responses (no more than 11%), and no more than 6 instances of 12-week PFS (no more than 33%), were observed among the initial 18 patients, the study would be terminated early and declared negative. Otherwise study will proceed to Stage II of accrual to a maximum of 36 patients. If at least 8 objective responses (at least 22%), or at least 16 instances of 12-week PFS (at least 44%), were observed among the 36 evaluable patients, this agent would be considered worthy of further testing in this disease.
GOG-0225 CAN DIET AND PHYSICAL ACTIVITY MODULATE OVARIAN, FALLOPIAN TUBE AND PRIMARY PERITONEAL CANCER
Ovarian cancer is diagnosed in approximately 22,430 women annually in the United States. The Gynecological Oncology Group affords a unique opportunity to test hypotheses relating dietary intake and increased physical activity to improved progression-free survival among women diagnosed with ovarian cancer.The lifestyle intervention, which consist of 20% total energy as dietary fat, greater than 6 colorful vegetables and fruit servings, plus 4,000+ additional steps daily, included in this protocol is consistent with national and international recommendations for cancer prevention and survival.Primay Objective:To determine if women who are disease-free after successfully completing primary and potential consolidation/maintenance, therapy for Stage II-IV ovarian, fallopian tube or primary peritoneal cancer and who are randomized to a healthy lifestyle intervention will have significantly increased progressionfree survival compared to similar women who are randomized to a usual carecomparison group.Study Population:Patients with a histological diagnosis of epithelial ovarian cancer, fallopian tube or primary peritoneal carcinoma, clinical stage II, III or IV at diagnosis.Study Arms:Women will be randomized 1:1 to intervention versus control and randomization will include stratification according to consolidation therapy (yes/no) as well as stage at diagnosis (II, III, or IV)Endpoints:Patients experiencing a recurrence of disease or a second primary cancer event will have reached the targeted study endpoint.Follow up:follow-up will be at 3 month intervals for the first 2 years, 6 month intervals for the next 3 years, and annually thereafter.Analysis:The overall effectiveness of the intervention will be assessed by a log-rank test stratified by stage of disease (II and III vs. IV) and consolidation therapy (yes or no). Progression-free survival time for those who are still alive and have not been observed to fail by study end will be treated as censored observations.
A Randomized Phase II/III Study of Paclitaxel/Carboplatin/Metformin (NSC#91485) versus Paclitaxel/Carboplatin/Placebo as Initial Therapy for Measurable Stage III or IVA, Stage IVB, or Recurrent Endometrial Cancer
This randomized phase II/III trial studies how well paclitaxel, carboplatin, and metformin hydrochloride works and compares it to paclitaxel, carboplatin, and placebo in treating patients with endometrial cancer that is stage III, IV, or has come back. Metformin hydrochloride may help paclitaxel and carboplatin work better by making cancer cells more sensitive to the drugs.
The primary ojective is to determine if the addition of metformin (metformin hydrochloride) to the standard regimen of carboplatin and paclitaxel prolongs progression-free survival (PFS) in women with advanced or recurrent endometrial cancer.
Women, 18 years or older with Stage III or IVA endometrial cancer with measurable disease
Stage IVB endometrial cancer, recurrent endometrial cancer and no prior chemotherapy.
Paclitaxel 175 mg/m2 IV over 3 hours day 1
Carboplatin AUC = 5 IV day 1
Metformin 850 mg oral QD, beginning on day 1. If tolerated for 4 weeks, the dose will be increased to Metformin 850 mg BID. Every 21 days x 6 cycles.
Maintenance regimen (for patients in complete response, partial response or stable disease) Metformin 850 mg oral BID (one cycle of maintenance therapy = 21 days)
Paclitaxel 175 mg/m2 IV over 3 hours day 1
Carboplatin AUC = 5 IV day 1
Placebo for metformin 850 mg oral QD, beginning on day 1. If tolerated for 4 weeks, the dose will be increased to placebo for metformin 850 mg BID. Every 21 days x 6 cycles.
Maintenance regimen (for patients in complete response, partial response or stable disease) Matched placebo oral BID (one cycle of maintenance therapy = 21 days)
Progression-free survival (PFS), (Phase II) [ Time Frame: From date of study entry to time of progression or death, whichever occurs first, assessed up to 5 years ]
Follow-up every 3 months for 2 years and then every 6 months for 3 years. Follow-up forms are collected for the 5 year follow-up period or until study termination.
This study will use an intent-to-treat principle with equal randomization to each treatment arm, balanced by performance status (0 or 1 versus 2), disease status (Stage III versus Stage IV or recurrent), and patient body mass index (BMI < 30 versus >=30). The study will accrue 240 patients and test the equivalence of PFS between the regimens after 60 PFS events are observed in the reference regimen at a 20% level of significance.
Assuming no interruption of accrual, this analysis will be conducted approximately when 60% of the targeted accrual is attained. If the futility analysis indicates a higher hazard of death on the experimental arm, then the trial could close at that time.
5C-11-2 Phase II Clinical Trial of Eribulin in Advanced or Recurrent Cervical Cancer
Cervical cancer is the second most common cancer in women worldwide; and, in developing countries, it is the leading cause of death by cancer. Treatment for advanced disease after the use of platinum based therapy yields low response and survival rates, therefore there is a huge need for the identification of active agents.. Eribulin is a targeted agent that inhibits cell growth in multiple types of cancers. Previous studies have shown that it improves response and survival rates. This study is a phase II, single arm, two-stage study using eribulin in patients with advanced cervical cancer. The primary objective of this study is to evaluate the effectiveness of eribulin in these patients.Patients with laboratory confirmed invasive cervical cancer who have had up to 1 previous chemotherapy regimen for advanced disease will be considered for this study. Once patients have agreed to participate, they will be screened for eligibility. Once they are deemed eligible, they will receive eribulin through a vein in the arm on Days 1 and 8 of a 21-day treatment cycle. They will have a study visits during each cycle that will include the following tests and procedures: blood tests, physical exams, vital signs, ECG to check their heart, evaluation of their ability to carry out everyday activities, and an evaluation of side effects. They will also have x-rays or CT/MRI scans to determine whether their tumor is growing. Tumor tissue from a previous biopsy or surgery and blood samples will be collected for research testing. Subjects will continue taking the study drug until their tumor grows or they have unacceptable side effects.Fifteeen patients will be treated and evaluated in the first stage; if 1 or more of the 15 patients achieves a progression free survival of 6 months, an additional 15 patients will be accrued into the second stage.The primary efficacy endpoint will be 6-month progression-free survival. The secondary efficacy endpoint will be best overall response. The occurrence of toxic death (TD) at any time will be a primary endpoint for safety monitoring. The study will be terminated if fewer than 1 out of 15 patients are progression-free at 6 months.
5GYN-11-1-A Phase 2 Evaluation of TRC105 in the Treatment of Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Carcinoma
Angiogenesis plays a central role in the progression of epithelial ovarian cancer. In mouse
models, VEGF-inhibitors diminish ovarian tumor growth, metastasis and malignant ascites
formation. Independent Phase 2 trials have demonstrated single-agent activity for bevacizumab
in recurrent ovarian cancer, and randomized controlled Phase 3 trials are ongoing in the
first-line setting (GOG 0218 and ICON-7) and for recurrent disease (GOG 0213, OCEANS).
TRC105 is an antibody to CD105, an important non-VEGF angiogenic target on vascular
endothelial cells. TRC105 inhibits angiogenesis, tumor growth and metastases in preclinical
models. In a Phase 1 study of advanced solid tumors, TRC105 therapy caused a global reduction
in angiogenic biomarkers and reduced tumor burden at doses that were well-tolerated. We
hypothesize that TRC105 will have single-agent activity in recurrent ovarian cancer. By
targeting a non-VEGF pathway, TRC105 has the potential to complement VEGF inhibitors which
could represent a major advance in ovarian cancer therapy.
A Phase II Trial of DCTD-Sponsored Dasatinib (NSC #732517 IND #120636) in Recurrent/Persistent Ovary, Fallopian Tube, Primary Peritoneal, and Endometrial Clear Cell Carcinoma Characterized for the Retention or Loss of BAF250a Expression
I. To assess the clinical activity of dasatinib in patients with recurrent or persistent
ovarian, fallopian tube, primary peritoneal, and endometrial clear cell carcinoma using
objective tumor response (complete and partial): in patients without loss of BRG-associated
factor 250a (BAF250a) expression and in patients with loss of BAF250a expression.
I. To examine the nature and degree of toxicity in this patient population treated with this
regimen in patients with and without loss of BAF250a expression.
II. To examine the progression-free survival and overall survival for this patient population
receiving dasatinib in patients with and without loss of BAF250a expression.
I. To examine the agreement between BAF250a immunohistochemistry and AT rich interactive
domain 1A (SWI-like) (ARID1A) mutation status using next generation sequencing performed in
formalin-fixed, paraffin-embedded tumor tissue.
Patients receive dasatinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28
days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 2 years and
then every 6 months for 3 years.
Active, not recruiting | Gynecologic Cancers | Multisite