A Randomized Phase II Study of Androgen Deprivation Versus Combined With IMC-A12 Versus Androgen Deprivation Alone for Patients With New Hormone-Sensitive Metastatic Prostate Cancer
18 Years
N/A
Male
Adenocarcinoma of the Prostate, Recurrent Prostate Cancer, Stage IV Prostate Cancer
Trial Information
A Randomized Phase II Study of Androgen Deprivation Versus Combined With IMC-A12 Versus Androgen Deprivation Alone for Patients With New Hormone-Sensitive Metastatic Prostate Cancer
PRIMARY OBJECTIVES:
I. To compare the undetectable PSA rate (PSA < 0.2 ng/mL) after seven cycles (28 weeks) of
protocol treatment between those randomized to a LHRH agonist and bicalutamide and those
randomized to a LHRH agonist, bicalutamide and IMC-A12.
Secondary I. To assess the safety and tolerability of the combination of IMC-A12 with a LHRH
agonist and bicalutamide.
II. To compare the proportion of men who do not achieve a PSA of < 4 ng/mL between the two
groups.
III. To assess the accuracy of the prognostic model of undetectable PSA that was developed
from SWOG-9346 using current trial data from each arm.
IV. To assess serum samples and peripheral blood mononuclear cells (PBMNC) for
pharmacodynamic activity with potential biomarkers for IMC-A12 (including, but not limited
to: IGF-I, free IGF-I, IGF-II, IGFBP2, IGFBP3, Growth Hormone, insulin and C-peptide)
obtained from optional blood specimens both before initiation of androgen deprivation
therapy and twelve weeks after initiation of combined therapy.
V. To determine baseline pre-treatment circulating tumor cell (CTC) quantities and response
to therapy (for those patients with detectable CTC levels ≥ 1) twelve weeks later.
VI. In the same subset of patients where CTC levels are obtained, determine baseline serum
levels of microRNAs to include but not limited to mi-141 both before initiation of androgen
deprivation therapy and twelve weeks after combined therapy.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive androgen deprivation therapy comprising oral bicalutamide once daily
on days 1-28 and either goserelin subcutaneously or leuprolide acetate intramuscularly every
1, 3, 4, 6, or 12 months. Patients also receive cixutumumab IV over 1 hour on days 1 and 15.
Treatment repeats every 28 days for 7 courses in the absence of disease progression or
unacceptable toxicity.
ARM II: Patients receive androgen deprivation therapy comprising bicalutamide and either
goserelin or leuprolide acetate as in arm I.
After completion of study therapy, patients are followed up every 6 months for 2 years and
then annually for 3 years.
Inclusion Criteria:
- Histologically or cytologically confirmed adenocarcinoma of the prostate
- Metastatic disease as evidenced by soft tissue and/or bony metastases, including
≥ 1 of the following:
- Visceral disease (liver, lung, or other viscera)
- Bone metastases to sites in either the axial (spine, pelvis, ribs, or
skull) and/or the appendicular (clavicle, humerus, or femur) skeleton
- Lymph node disease not considered to be encompassed within a single
radiotherapy port (e.g., above the aortic bifurcation)
- Patients with measurable disease must have radiographic assessment (at least an
abdominal/pelvic CT scan) within the past 28 days
- Patients with non-measurable disease must be assessed (e.g., bone scan) within
the past 42 days
- PSA ≥ 5 ng/mL within 90 days before initiation of androgen-deprivation therapy
- No known brain metastases
- Brain imaging studies not required for patients with no neurologic signs or
symptoms
- Zubrod performance status (PS) 0-2
- Zubrod PS 3 allowed if due to bone pain
- WBC ≥ 3,000/mm^3
- ANC ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Hemoglobin ≥ 9 g/dL
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- AST and ALT ≤ 3 times ULN (≤ 5 times ULN for liver metastases)
- Creatinine ≤ 2.0 times ULN OR creatinine clearance ≥ 40 mL/min
- INR ≤ 1.5
- PTT ≤ 5 seconds above the ULN
- Hemoglobin A1c (HgA1C) ≤ 7 AND fasting glucose < 160 mg/dL or below ULN
- Patients with diabetes mellitus who meet this criterion are eligible provided
they are on a stable dietary or therapeutic regimen
- Fertile patients must use effective contraception during and for ≥ 3 months after
completion of study therapy
- No known LVEF ≥ 10% below the lower limit of normal
- Patients with suspected LV dysfunction not confirmed by review of medical
history must undergo MUGA or ECHO within 90 days before study entry
- No history of symptomatic congestive heart failure
- No history of allergic reaction attributed to compounds of similar chemical or
biological composition to cixutumumab
- No other malignancy within the past 5 years except adequately treated basal cell or
squamous cell skin cancer or stage I or II cancer currently in complete remission
- Prior medical castration allowed provided it was initiated within the past 30 days
- Patients on a luteinizing hormone-releasing hormone (LHRH) agonist (e.g.,
leuprolide acetate or goserelin) must be willing to continue the LHRH agonist in
addition to bicalutamide during study treatment
- Patients on a different anti-androgen (e.g., flutamide) must be willing change
to bicalutamide during study treatment
- Prior bilateral orchiectomy allowed provided it was performed within the past 30 days
- At least 28 days since prior non-orchiectomy surgery and recovered
- More than 28 days since prior strontium-89, rhenium-186, rhenium-188, or samarium-153
radionuclide therapy
- At least 28 days since prior radiotherapy or biologic therapy (e.g., vaccines,
immunotherapy, anti-sense agents, small molecules, or monoclonal antibodies) and
recovered
- No prior cytotoxic chemotherapy for metastatic prostate cancer
- No prior treatment with agents that directly inhibit IGF or IGFR
- No prior chimerized or murine monoclonal antibody therapy
- No concurrent antiretroviral therapy for HIV-positive patients
- No concurrent treatment with any of the following:
- Chemotherapy
- Hormonal therapy (other than the LHRH agonist and oral anti-androgen)
- Radiotherapy
- Immunotherapy
- Any other anticancer therapy
- 5-alpha reductase inhibitors (e.g., finasteride or dutasteride)
- Ketoconazole
- Diethylstilbestrol/DES
- Other estrogen-based therapy
- Concurrent prophylactic low-dose coumadin or low-molecular weight heparin allowed
provided coagulation criteria are met
- Patients requiring full-dose (therapeutic) anticoagulation are eligible provided
they are on a stable dose of anticoagulation AND the coagulation parameters are
stable within the therapeutic range (e.g., INR 2-3 for patients on therapeutic
warfarin)
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Undetectable PSA rate
Outcome Time Frame:
7 months
Safety Issue:
No
Principal Investigator
Evan Yu
Investigator Role:
Principal Investigator
Investigator Affiliation:
Southwest Oncology Group
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2011-02003
NCT ID:
NCT01120236
Start Date:
December 2010
Completion Date:
Related Keywords:
- Adenocarcinoma of the Prostate
- Recurrent Prostate Cancer
- Stage IV Prostate Cancer
- Adenocarcinoma
- Adenocarcinoma, Mucinous
- Prostatic Neoplasms
Name | Location |
|---|---|
| H. Lee Moffitt Cancer Center and Research Institute | Tampa, Florida 33612 |
| Tripler Army Medical Center | Honolulu, Hawaii 96859-5000 |
| Genesys Hurley Cancer Institute | Flint, Michigan 48503 |
| Virginia Mason CCOP | Seattle, Washington 98101 |
| Evergreen Hospital Medical Center | Kirkland, Washington 98033 |
| Spectrum Health Reed City Hospital | Reed City, Michigan 49677 |
| Pacific Medical Center-First Hill | Seattle, Washington 98104 |
| Fairbanks Memorial Hospital | Fairbanks, Alaska 99701 |
