A Phase III Randomized, Double-Blind Trial of Chemoembolization With or Without Sorafenib in Unresectable Hepatocellular Carcinoma (HCC) in Patients With and Without Vascular Invasion
PRIMARY OBJECTIVE:
I. To compare progression-free survival (PFS) of chemoembolization alone to sorafenib
(sorafenib tosylate) in combination with chemoembolization.
SECONDARY OBJECTIVES:
I. To compare overall survival (OS) of chemoembolization alone to sorafenib in combination
with chemoembolization.
II. To evaluate extra-hepatic versus intra-hepatic patterns of failure. III. To determine
the rates of toxicity related to sorafenib in combination with chemoembolization.
TERTIARY OBJECTIVES:
I. To analyze the pharmacogenetic and pharmacokinetic properties of sorafenib including
angiogenesis, monooxygenases, polymorphisms and multidrug resistance (MDR).
II. Eastern Cooperative Oncology Group (ECOG)-American College of Radiology Imaging Network
(ACRIN) secondary imaging objective: site vs. central evaluation of PFS.
III. To determine the inter-reader concordance for response characterization at four and
eight months by the European Association for the Study of Liver (EASL) criteria.
IV. To determine the value of objective tumor response at four and eight months by the EASL
criteria to predict PFS (by Response Evaluation Criteria in Solid Tumors [RECIST]) and OS.
V. To evaluate the effects of intra-hepatic vs. extra-hepatic progression on OS.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive sorafenib tosylate orally (PO) twice daily (BID) in the absence of
disease progression or unacceptable toxicity. Beginning within 2 weeks after a stable dose
of sorafenib tosylate is reached, patients undergo transarterial chemoembolization (TACE)
comprising doxorubicin hydrochloride, mitomycin C, and cisplatin (closed to accrual as of
10/1/2010); conventional chemoembolization comprising doxorubicin hydrochloride only; or
chemoembolization comprising doxorubicin-eluting beads. Treatment with TACE repeats
approximately every 4 weeks for up to 4 courses in the absence of disease progression or
unacceptable toxicity.
ARM II: Patients receive placebo PO BID in the absence of disease progression or
unacceptable toxicity. Beginning within 2 weeks after a stable dose of placebo is reached,
patients undergo TACE as in Arm I.
MAINTENANCE THERAPY: After completion of chemoembolization, patients receive sorafenib
tosylate or placebo as in Arm I and II in the absence of disease progression or unacceptable
toxicity.
After completion of study treatment, patients are followed up for 4 years.
A Randomized Phase III Trial of the Value of Early Local Therapy for the Intact Primary Tumor in Patients With Metastatic Breast Cancer
OBJECTIVES:
Primary
- To evaluate whether early local therapy comprising surgery of intact primary disease
compared to local palliative therapy only in patients with stage IV breast cancer,
whose disease does not progress during initial optimal systemic therapy, will result in
prolonged survival.
Secondary
- To compare the time to uncontrolled chest wall disease between patients treated with
these regimens.
- To determine whether there is a difference in health-related quality-of-life (HRQOL)
between patients treated with these regimens.
- To determine whether the absolute value of circulating tumor cells (CTC) burden at 6
months following randomization (time +6) will be lower in the palliative therapy arm
than in early local therapy arm, and whether this value is inversely related to
survival (lower CTC, longer survival).
- To collect tumor and blood specimens for future exploration of the biological
interactions between the primary tumor and metastatic lesions and the effect of primary
tumor resection.
OUTLINE: This is a multicenter study. Patients are stratified according to hormone receptor
and treatment plan (ER+ or PR+, HER2-, endocrine therapy alone vs ER+ or PR+, and HER2-,
chemotherapy and/or endocrine therapy vs ER- or PR-, and HER2- vs HER2+), and number of
involved organ systems with distant disease (regional nodes in the axillary,
supraclavicular, and internal mammary locations are not considered distant sites) (1 vs >
1). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive standard palliative therapy, if needed, to address symptoms
such as tumor ulceration, pain, bulky adenopathy causing arm symptoms, and other
similar situations. Therapy may consist of radiotherapy alone, surgery alone, or a
combination of both.
- Arm II: Patients undergo surgery comprising breast-conserving therapy (BCT) or total
mastectomy according to patient and treating physician preference. Surgery is to occur
no later than 10 weeks after completion of 32 weeks of systemic therapy. Free surgical
margins must be achieved with re-excision or mastectomy for patients undergoing BCT.
After completion of BCT, patients undergo radiotherapy once a day, 5 days per week.
Patients who had mastectomy undergo radiotherapy at the discretion of treating
physician.
Patients may undergo blood and tumor tissue sample collection for circulating tumor cells
(CTC) burden and future studies.
Patients complete the Functional Assessment of Cancer Therapy - Breast Trial Outcome Index
(FACT- TOI) and FACT - General (22) and the Breast Cancer Subscale (FACT-B) quality-of-life
questionnaires at baseline and periodically during study.
After completion of study therapy, patients are followed up periodically for 5 years.
A Phase II-R and a Phase III Trial Evaluating Both *Erlotinib (PH II-R) and Chemoradiation (PH III) as Adjuvant Treatment For Patients With Resected Head of Pancreas Adenocarcinoma
PRIMARY OBJECTIVES:
I. To determine whether the addition of erlotinib (erlotinib hydrochloride) to gemcitabine
(gemcitabine hydrochloride) adjuvant chemotherapy shows a signal for improved survival as
compared to gemcitabine alone following R0 or R1 resection of head of pancreas
adenocarcinoma (including adenocarcinoma of the head, neck, and uncinate process). (Phase
II-R) II. To determine whether the use of concurrent fluoropyrimidine and radiotherapy
following adjuvant gemcitabine hydrochloride-based chemotherapy further enhances survival
for such patients who are without evidence of progressive disease after 5 cycles of
gemcitabine based chemotherapy. (Phase III)
SECONDARY OBJECTIVES:
I. To evaluate disease-free survival of adjuvant chemotherapy followed by radiotherapy and
concurrent fluoropyrimidine for patients with resected head of pancreas adenocarcinoma who
are disease free after 5 cycles of adjuvant chemotherapy.
II. To evaluate disease-free survival of standard adjuvant gemcitabine chemotherapy with and
without erlotinib for patients with resected head of pancreas adenocarcinoma.
III. To evaluate adverse events with and without erlotinib for patients with resected head
of pancreas adenocarcinoma.
IV. To evaluate adverse events of adjuvant chemotherapy with or without radiation therapy
and concurrent fluoropyrimidine for patients with resected head of pancreas adenocarcinoma
who are disease free after adjuvant chemotherapy.
V. To evaluate preoperative cross-sectional imaging of the primary head of pancreas
adenocarcinoma in order to determine the frequency with which objective criteria of
resectability are present.
VI. To determine if patients reporting low baseline fatigue, as measured by the Functional
Assessment of Chronic Illness Therapy (FACIT)-Fatigue, predicts survival and to explore
correlations between baseline fatigue, as measured by Patient-Reported Outcomes Measurement
Information System (PROMIS), and survival.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on days
1, 8, and 15. Treatment repeats every 28 days for 5 courses in the absence of disease
progression or unacceptable toxicity.
ARM II: Patients receive gemcitabine hydrochloride as in arm I and erlotinib hydrochloride
orally (PO) once daily on days 1-28. Treatment repeats every 28 days for 5 courses in the
absence of disease progression or unacceptable toxicity. (NOTE: Phase II-R erlotinib
hydrochloride randomization completed, Arm 2 closed to accrual effective 2/19/2014)
Patients with no disease progression after treatment in arm I or II are then stratified
according to their first randomization treatment arm (arm I vs arm II) and randomized to 1
of 2 additional treatment arms (arm III or IV).
ARM III: Patients receive 1 course of the same treatment that they receive in arm I or II.
ARM IV: Patients receive 1 course of the same treatment that they receive in arm I or II.
Beginning within 7-21 days after completion of chemotherapy, patients undergo radiotherapy
(3-dimensional conformal radiotherapy or intensity-modulated radiotherapy) 5 days per week
for 5.5 weeks (28 fractions). During radiotherapy, patients receive either capecitabine PO
twice daily (BID) 5 days per week or fluorouracil IV continuously for 5.5 weeks or until
radiotherapy is completed.
After completion of study treatment, patients are followed up periodically.
A Phase III Prospective Randomized Trial of Dose-Escalated Radiotherapy With or Without Short-Term Androgen Deprivation Therapy for Patients With Intermediate-Risk Prostate Cancer
OBJECTIVES:
Primary
- Demonstrate an overall survival (OS) advantage in patients with intermediate-risk
prostate cancer treated with dose-escalated radiotherapy (RT) with versus without
short-term androgen-deprivation therapy (ADT).
Secondary
- Determine whether the addition of ADT to dose-escalated RT versus RT alone improves
clinical failures, biochemical failure by the "nadir +2", freedom from failure, rate of
salvage ADT, and prostate cancer-specific mortality in these patients.
- Estimate the magnitude of benefit of ADT with respect to OS in patients treated with
different RT modalities (i.e., external-beam radiation therapy alone vs low-dose rate
brachytherapy boost vs high-dose rate brachytherapy boost).
- Compare acute and late treatment adverse events of these regimens and correlate these
events with the presence or absence of pre-existing comorbidity as documented by the
Adult Comorbidity Evaluation 27 assessment.
OUTLINE: This is a multicenter, dose-escalation study of radiotherapy. Patients are
stratified according to number of risk factors (1 vs 2-3), comorbidity (ACE-27 grade ≥ 2 vs
< 2), and radiotherapy (RT) modality (dose-escalated external-beam RT [EBRT] vs EBRT and
low-dose rate brachytherapy boost vs EBRT and high-dose rate brachytherapy boost). Patients
are randomized to 1 of 2 treatment arms.
- Arm I: Patients undergo EBRT* once daily on days 1-5 for about 9 weeks (44 treatments).
Some patients instead receive EBRT with high-dose rate or low-dose rate brachytherapy
implant on days 1-5 for about 5 weeks (25 treatments). NOTE: *Type of RT is at
discretion of treating physician and may include either 3D-conformal RT or
intensity-modulated RT.
- Arm II: Patients receive androgen-deprivation therapy comprising luteinizing-hormone
releasing-hormone (LHRH) agonist (leuprolide, goserelin, buserelin, or triptorelin)
subcutaneously or as an injection every 1 to 3 months AND an oral antiandrogen therapy
(flutamide 3 times daily or bicalutamide once daily) for 6 months. Beginning 8 weeks
after the first LHRH injection, patients undergo radiotherapy as in arm I.
After completion of study therapy, patients are followed up periodically.
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