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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


Phase 2
18 Years
N/A
Open (Enrolling)
Male
Adenocarcinoma of the Prostate, Recurrent Prostate Cancer, Stage IV Prostate Cancer

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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 InstituteTampa, Florida  33612
Tripler Army Medical CenterHonolulu, Hawaii  96859-5000
Genesys Hurley Cancer InstituteFlint, Michigan  48503
Virginia Mason CCOPSeattle, Washington  98101
Evergreen Hospital Medical CenterKirkland, Washington  98033
Spectrum Health Reed City HospitalReed City, Michigan  49677
Pacific Medical Center-First HillSeattle, Washington  98104
Fairbanks Memorial HospitalFairbanks, Alaska  99701