Phase II Study of Metformin in a Pre-prostatectomy Prostate Cancer Cohort
I. To determine the effect of 4-12 weeks of metformin (metformin hydrochloride) intervention
on cell proliferation in the prostatectomy tissue.
I. To determine the effect of metformin intervention on prostate tissue bioavailability of
II. To determine the effect of metformin intervention on apoptosis and angiogenesis in the
III. To determine the effect of metformin intervention on potential molecular targets of
metformin including activated protein kinase (AMPK) activation, mammalian target of rapamycin
(mTOR) regulation, and cell cycle regulation in the prostatectomy tissue.
IV. To determine the effect of metformin intervention on changes in systemic hormones and
growth factors that have been shown to be modulated by metformin in other patient populations
including fasting glucose, fasting insulin, insulin-like growth factor axis, testosterone,
and sex hormone binding globulin (SHBG).
V. To determine the effect of metformin intervention on changes in prostate-specific antigen
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive extended-release metformin hydrochloride orally (PO) once daily (QD)
for 4-12 weeks.
ARM II: Patients receive placebo PO QD for 4-12 weeks.
Patients in both arms undergo surgery one day after completion of treatment.
After completion of study treatment, patients are followed up within 30 days of surgery.
Phase II Randomized Trial of ABT-888 in Combination With Metronomic Oral Cyclophosphamide in Refractory BRCA-Positive Ovarian, Primary Peritoneal, Ovarian High-Grade Serous Carcinoma, Fallopian Tube Cancer, or Triple-Negative Breast Cancer
- 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.
Phase 2 Trial of Phenelzine in Non-metastatic Recurrent Prostate Cancer
I. To assess the proportion of patients with biochemical recurrent prostate cancer (BCR-PC)
treated with phenelzine (phenelzine sulfate) who achieve a prostate-specific antigen (PSA)
decline of >= 50% from baseline.
I. To monitor potential toxicities and/or beneficial effects on quality of life of phenelzine
in prostate cancer patients.
II. To assess time to radiographic disease progression for patients with recurrent prostate
cancer treated with phenelzine.
III. To collect blood and other samples to study the relationship between MAO activity and
Patients receive phenelzine sulfate 30 mg by mouth (PO) twice daily (BID) (starting dose of
15 mg daily escalated to 30 mg BID over 16 plus or minus 5 days). Patients who have been
treated at 30 mg BID for over 3 cycles with resolution of any and all toxicities to grade <
or = 1 may increase the dose to a maximum of 45 mg BID at the discretion of the treating
investigator. Treatment may continue in the absence of disease progression or unacceptable
After completion of study treatment, patients are followed up every 3 months for up to 3
EVEREST: EVErolimus for Renal Cancer Ensuing Surgical Therapy, A Phase III Study
- to compare recurrence-free survival in renal carcinoma patients randomly assigned to 54
weeks of everolimus versus 54 weeks of placebo after nephrectomy or partial nephrectomy.
- To compare the overall survival of patients treated with everolimus vs placebo.
- To compare qualitative and quantitative toxicity between the two study arms.
- To bank tissue and biologic specimens for future study of molecular biomarkers relevant
to the AKT/mTOR and other pathways implicated in the pathogenesis of renal carcinoma and
to investigate their potential predictive and prognostic value.
- To bank blood specimens for the future study of the relationship between steady-state
trough levels of everolimus and relevant side effects (lymphopenia, infection,
hyperglycemia, hypercholesterolemia, hypertriglyceridemia) in patients treated on this
study with everolimus.
OUTLINE: This is a multicenter study.
Patients are stratified according to pathologic stage (intermediate high-risk vs very
high-risk), histologic subtype (clear cell vs non-clear cell), and performance status (0 vs
1). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive oral everolimus once daily on days 1-42. Treatment repeats every
6 weeks for 9 courses in the absence of disease progression or unacceptable toxicity.
- Arm II: Patients receive oral placebo once daily on days 1-42. Treatment repeats every 6
weeks for 9 courses in the absence of disease progression or unacceptable toxicity.
Archived tumor tissue, plasma, and whole blood samples may be collected periodically for
biomarker analysis and other translational studies.
After completion of study treatment, patients are followed up every 6 months for 2 years and
then annually for 8 years.
Phase II Clinical Trial of Eribulin in Advanced or Recurrent Cervical Cancer
I. To evaluate the activity of eribulin (eribulin mesylate) in the management of advanced or
recurrent cervical cancer (progression-free survival [PFS].
I. To describe the toxicity profile of eribulin in patients with advanced or recurrent
II. To estimate the survival of patients with advanced or recurrent cervical cancer treated
III. To evaluate potential correlative studies as predictive or prognostic makers in this
patient population (glucose-regulated protein 78 [GRP78] levels in tissue and blood, tumor
protein p53 [p53] expression, apoptosis with terminal deoxynucleotidyl transferase dUTP nick
end labeling [TUNEL] assay, apoptosis-related proteins B-cell lymphoma 2 [Bcl-2] and
Bcl2-associated X protein [Bax] using immunohistochemistry [IHC], proliferation with Ki-67
IHC, and expression levels of microtubule-associated variables, including tau protein, total
alpha- and beta-tubulin, and classes II-IV beta-tubulin isotopes with IHC.
OUTLINE: Patients receive eribulin mesylate 1.4 mg/m2 intravenously (IV) bolus over 2-5
minutes on days 1 and 8. Courses repeat every 21 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.
Genomics of Young Lung Cancer Study
I. To perform comprehensive genomic analysis of young lung cancer patients' samples to
facilitate delivery of targeted therapies and clinical trial enrollment.
II. To characterize the impact of young age at lung cancer diagnosis on the genomic landscape
of primary lung cancer.
III. To establish a prospective registry of young lung cancer patients for both tumor and
germline next generation sequencing.
Tissue and blood samples are analyzed via next generation sequencing and whole exome
After completion of study, patients are followed up every 3 months for up to 3 years.
18F-FMAU for Imaging in Cancer Patients
I. To determine the radiation dosimetry of 18F-FMAU in humans, confirm absence of adverse
events in humans from intravenous (i.v.) injection of 18F-FMAU for PET imaging, and
characterize the incidence of circulating metabolites of 18F-FMAU in humans.
II. To simply find out whether there is any visual uptake change of 18F-FMAU in tumors
Patients receive fluorine F 18 d-FMAU IV followed by PET/CT prior to start of cancer
treatment. Patients may undergo 2 additional scans at one week prior to second course of
chemotherapy and after completion of cancer treatment depending on cancer type.
A Mindfulness-Based Educational Intervention For Colorectal Cancer Patients And Caregivers
I. To evaluate the effect of a brief educational program on colorectal cancer knowledge
acquisition in a 3-arm randomized clinical trial (Control Group: standard of care; Treatment
Group 1: cancer education; Treatment Group 2: mindfulness + cancer education) comparing
visual/written educational material with and without mindfulness training to the standard of
II. To determine the priming effect of a brief mindfulness training on retaining knowledge
of colorectal cancer education.
III. To determine the joint effect of colorectal cancer education delivered to both the
patient and a caregiver on the overall colorectal cancer knowledge.
I. To examine the relative changes in psychobiological variables (stress, anxiety,
depression, mindfulness, fatigue, life benefit) from pre (T0) to post (T1) intervention in
the 3 arms of the clinical trials.
II. To measure changes in salivary cortisol levels as an indicator of acute stress
reactivity across 4 time points across a one-hour period (i.e., 0 min, 20 min, 40 min, 60
min) during active chemotherapy (T1).
III. To determine the moderating effect of baseline peripheral levels of inflammation
(interleukin-1 [IL-1], IL-6, c-reactive protein [CRP] and tumor necrosis factor alpha
[TNFa]) on the trajectory of salivary cortisol reactivity.
OUTLINE: Patients and caregivers are randomized to 1 of 3 groups.
GROUP I: Patients and caregivers receive standard of care.
GROUP II: Patients and caregivers receive a 20-minute self-playing interactive educational
GROUP III: Patients and caregivers receive a 20-minute self-playing interactive educational
video brochure and watch a 20-minute interactive mindfulness exercise video.
Not recruiting | Colon / Rectal Cancer | Not Multisite
A Multicenter Trial of FDG-PET/CT Staging of Head and Neck Cancer and Its Impact on the N0 Neck Surgical Treatment in Head and Neck Cancer Patients
- Determine the negative predictive value of PET/CT imaging based upon pathologic
sampling of the neck lymph nodes in patients with head and neck cancer planning to
undergo N0 neck surgery.
- Determine the potential of PET/CT imaging to change treatment.
- Estimate the sensitivity and diagnostic yield of PET/CT imaging for detecting occult
metastasis in the clinical N0 neck (both by neck and lymph node regions) or other local
- Determine the effect of other factors (e.g., tumor size, location, secondary primary
tumors, or intensity of FDG uptake) that can lead to identification of subsets of
patients that could potentially forego neck dissection or that can provide preliminary
data for subsequent studies.
- Compare the cost-effectiveness of using PET/CT imaging for staging head and neck cancer
vs current good clinical practices.
- Evaluate the incidence of occult distant body metastasis discovered by whole-body
- Correlate PET/CT imaging findings with CT/MRI findings and biomarker results.
- Evaluate the quality of life of these patients, particularly of those patients whose
management could have been altered by imaging results.
- Evaluate PET/CT imaging and biomarker data for complementary contributions to
metastatic disease prediction.
- Compare baseline PET/CT imaging and biomarker data with 2-year follow up as an adjunct
assessment of their prediction of recurrence, disease-free survival, and overall
- Determine the proportion of neck dissections that are extended (i.e., additional levels
that clinicians intend to dissect beyond the initial surgery plan) based on
local-reader PET/CT imaging findings shared with the surgeon before dissection.
- Estimate the optimum cutoff value of standardized uptake values for diagnostic accuracy
of PET/CT imaging.
- Evaluate the impact of PET/CT imaging on the N0 neck across different tumor subsites
(defined by anatomic location).
OUTLINE: This is a multicenter study.
Patients undergo fludeoxyglucose F 18-PET/CT imaging. Approximately 14 days later, patients
undergo unilateral or bilateral neck dissection.
Patients complete quality-of-life questionnaires at baseline and at 1, 12, and 24 months
Patients undergo blood and tissue sample collection periodically for biomarker analysis.
Patients are followed up periodically for up to 2 years after surgery.
Not recruiting | Head and Neck Cancers | Multisite
Combined Exercise Program for Early Breast Cancer Survivors
I. To determine whether a 16-week exercise intervention will improve components of
metastasis (MetS) in breast cancer survivors soon after completion of cancer-related
treatments by measuring changes in body composition, waist circumference, blood pressure,
and serum levels of insulin, glucose, lipids, C-reactive protein, and hemoglobin A1c
II. To determine whether a 16-week exercise intervention will improve physical fitness in
breast cancer survivors soon after completion of cancer-related treatments by measuring
cardiorespiratory fitness and muscle strength.
III. To assesses the feasibility of a supervised exercise intervention in early breast
IV. To determine whether a 16-week exercise intervention will result in a reduction in
adipose tissue inflammation in obese breast cancer survivors soon after completion of
cancer-related treatments by measuring ATM phenotype and ATM cytokine expression.
V. To determine whether breast cancer survivors can maintain positive benefits of an
exercise intervention following a 12-week follow-up period by measuring changes in body
composition, waist circumference, blood pressure, and serum levels of insulin, glucose,
lipids, C-reactive protein, and HbA1c, cardiorespiratory fitness and muscle strength.
Patients are randomized to 1 of 2 arms.
Arm I (Control): Patients refrain from increasing physical activity levels for 16 weeks.
Arm II (Exercise): Patients participate in supervised exercise sessions over 60 minutes
thrice weekly and are encouraged to participate in a home-based exercise session over 30-45
minutes once weekly for 16 weeks.
Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial (ALCHEMIST)
I. To centrally test resected non-small cell lung cancer (NSCLC) for genetic mutations to
facilitate accrual to randomized adjuvant studies.
II. To obtain clinically annotated tumor tissue and patient-matched non-malignant
deoxyribonucleic acid (DNA) from peripheral blood, as well as detailed epidemiologic and
clinical follow-up data, to allow clinically annotated advanced genomic analyses in concert
with the National Cancer Institute (NCI) Center for Cancer Genomics (CCG).
I. To characterize the natural history of molecularly characterized NSCLC to allow subsequent
development of targeted therapies against genotype-defined subpopulations in the adjuvant and
II. To cross-validate local genotyping assays for epidermal growth factor receptor (EGFR) and
anaplastic lymphoma receptor tyrosine kinase (ALK) with a central reference standard.
I. To study the genomic evolution of lung cancers by comparing genomic characteristics at
resection and at recurrence.
II. To understand reasons behind lack of enrollment to adjuvant targeted therapy studies for
potentially eligible patients.
III. To study the clinical significance of circulating tumor DNA within the plasma cell-free
DNA (cfDNA) from early stage lung cancer patients.
STEP 1 (SCREENING): Patients undergo collection of blood and tissue samples for EGFR, ALK,
and programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1)/cytotoxic
t-lymphocyte-associated protein 4 (CTLA-4) testing via direct sequencing, fluorescence in
situ hybridization (FISH) and immunohistochemistry (IHC). Patients that have had surgery
prior to pre-registration will submit samples from the previous surgery for testing.
STEP 2 (TREATMENT): Patients with a mutation targeted by one or more of the investigational
drugs used in this study or those without mutations are assigned to 1 of 3 treatment
A081105: Patients are randomized to 1 of 4 treatment arms.
ARM A (BLINDED ERLOTINIB- CLOSED 06/14/17): Blinded patients receive erlotinib hydrochloride
orally (PO) once daily (QD) on days 1-21. Treatment repeats every 21 days for up to 2 years
in the absence of disease progression or unacceptable toxicity.
ARM B (PLACEBO- CLOSED 06/14/17): Patients receive placebo PO QD on days 1-21. Treatment
repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable
ARM C (UNBLINDED ERLOTINIB): Unblinded patients receive erlotinib hydrochloride PO QD on days
1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression
or unacceptable toxicity.
ARM D (OBSERVATION): Patients (including patients previously randomized to placebo) undergo
observation at least every 6 months for 2 years.
E4512: Patients are randomized to 1 of 2 treatment arms.
ARM A: Patients receive crizotinib PO twice daily (BID) on days 1-21. Treatment repeats every
21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
ARM B: Patients undergo observation.
EA5142: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive nivolumab intravenously (IV) over 30 minutes on day 1. Courses repeat
every 4 weeks for up to 1 year in the absence of disease progression or unacceptable
ARM II: Patients are followed serially with imaging for 1 year.
After completion of study, patients that are not enrolled on either A081105, E4512, or EA5142
are followed up every 6 months for 5 years.
Assessment of Novel Biomarkers in Patients With Metastatic Castration Resistant Prostate Cancer
I. Perform molecular analysis of plasma samples from 25 patients with metastatic prostate
cancer collected before and during treatment of the disease with abiraterone acetate
(Zytiga) or enzalutamide (Xtandi).
II. Perform molecular characterization of circulating tumor cells (CTCs) and plasma
collected from 75 patients with progressing advanced metastatic prostate cancer.
OUTLINE: Patients are assigned to 1 of 2 groups based on the timing of specimen collection.
GROUP I: Previously collected plasma samples are analyzed for ctDNA via polymerase chain
reaction (PCR) and next generation sequencing (NSG).
GROUP II: Patients undergo collection of blood samples before and following systemic therapy
for analysis of CTC enumeration, ribonucleic acid (RNA) expression, and ctDNA via PCR and