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A Phase II Study of CTLA Blockade by Ipilimumab Plus Androgen Suppression Therapy in Patients With an Incomplete Response to AST Alone for Metastatic Prostate Cancer

Phase 2
18 Years
Open (Enrolling)
Adenocarcinoma of the Prostate, Hormone-resistant Prostate Cancer, Recurrent Prostate Cancer, Stage IV Prostate Cancer

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Trial Information

A Phase II Study of CTLA Blockade by Ipilimumab Plus Androgen Suppression Therapy in Patients With an Incomplete Response to AST Alone for Metastatic Prostate Cancer


I. Proportion of patients who achieve an undetectable prostate-specific antigen (PSA) (=<
0.2 ng/ml) after initiation of ipilimumab therapy.


I. Time to PSA progression. II. Time to progression by any measure. III. Maximum percentage
of PSA reduction in each patient. IV. Number of patients with immune related adverse events
(IRAEs) and correlation of these with complete PSA response, time to progression, and T cell

V. Measures of T cell response to therapy with flow cytometry. VI. Response in measurable
disease by modified Response Evaluation Criteria In Solid Tumors (RECIST) criteria.

VII. Time to death from any cause. VIII. To examine correlative biomarkers and their
relationship to clinical outcomes. Potential biomarkers include, but are not limited to
C-reactive protein (CRP), insulin-like growth factor (IGF)-1 and -2, or follicle-stimulating
hormone (FSH).


Patients receive ipilimumab intravenously (IV) over 90 minutes on day 1. Treatment repeats
every 21 days for up to 4 courses in the absence of disease progression or unacceptable
toxicity. Patients without progression then receive maintenance ipilimumab IV once every 3
months for four additional doses.

After completion of study treatment, patients are followed up every 3 months for up to 5

Inclusion Criteria:

- Willing and able to give written informed consent

- Histologic diagnosis of adenocarcinoma of the prostate

- A PSA of > 0.2 ng/ml after 6-18 months of androgen suppression therapy, which may
consist of luteinizing hormone-releasing hormone (LHRH) agonist or antagonist alone
or the combination of an LHRH agonist or antagonist plus an antiandrogen, such as
bicalutamide; androgen suppression therapy will continue without interruption

- Radiographic evidence of regional or distant metastasis at the time of study
enrollment or at the time of diagnosis

- White blood cell (WBC) >= 2000/uL

- Absolute neutrophil count (ANC) >= 1000/uL

- Platelets >= 50 x 10^3/uL

- Hemoglobin >= 8 g/dL

- Creatinine =< 3.0 x upper limit of normal (ULN)

- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 *ULN for
patients without liver metastasis

- Bilirubin =< 3.0 x ULN, (except patients with Gilbert's Syndrome, who must have a
total bilirubin less than 3.0 mg/dL)

- No known active or chronic infection with human immunodeficiency virus (HIV),
hepatitis B, or hepatitis C; patients should be assessed for high risk behaviors that
may result in these infections, such as intravenous drug use or multiple sexual
partners; the assessment should be noted

- Eastern Cooperative Oncology Group (ECOG) =< 1

- Patients receiving any herbal product known to decrease PSA levels (i.e. saw palmetto
and prostate cancer [PC]-SPES), or any immunosuppressive dose of systemic or
absorbable topical corticosteroid (except prednisone up to 10 mg orally per [q] day,
or its equivalent), must discontinue the agent for at least 2 weeks prior to
screening; progressive disease must be documented after discontinuation of these

- Patients receiving bisphosphonate therapy must have been on stable doses for at least
4 weeks with stable symptoms prior to the first infusion with ipilimumab

- Total testosterone < 50 ng/ml, except in patients with prior orchiectomy, where
testosterone does not need to be measured; patients must continue their LHRH agonist
therapy throughout study duration

- Life expectancy >= 6 months; this must be documented

- Patients who are sexually active with a partner who could become pregnant are to use
an effective form of barrier contraception, such as condoms or a partner using oral
contraceptive pills; persons of reproductive potential must agree to use an adequate
method of contraception throughout treatment and for at least 8 weeks after
ipilimumab is stopped

- If a patient enters the trial on androgen suppression therapy (AST) that consists of
both an LHRH agonist and an oral antiandrogen, both agents should be continued
throughout the study; if an antiandrogen is stopped prior to study entry, it should
be stopped 4 weeks before for nilutamide and flutamide and 6 weeks before for
bicalutamide to ensure that a withdrawal phenomenon does not interfere with
interpretation of efficacy results

Exclusion Criteria:

- Prior history of pelvic radiation associated with significant radiation proctitis
within 12 months prior to planned first infusion of ipilimumab; for the purpose of
this protocol, radiation proctitis is defined as diarrhea that reached a level of
grade 2 or grade 3, that occurred within one month of radiation treatment, and that
was of 7 days duration or longer

- Radiation to any area of the body < 28 days prior to randomization

- Any other active malignancy with the exception of adequately treated basal or
squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the

- Autoimmune disease: Patients with a history of inflammatory bowel disease are
excluded from this study, as are patients with a history of symptomatic disease (eg,
rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus
erythematosus, autoimmune vasculitis [eg, Wegener's Granulomatosis]); motor
neuropathy considered of autoimmune origin (e.g. Myasthenia Gravis, Guillain-Barre
Syndrome); those with immune-mediated skin toxicity (i.e. Toxic Epidermal Necrolysis,
Stevens-Johnson Syndrome) will also be excluded

- Any underlying medical or psychiatric condition, which in the opinion of the
investigator will make the administration of ipilimumab hazardous or obscure the
interpretation of adverse events (AEs), such as a condition associated with frequent

- Any non-oncology vaccine therapy used for prevention of infectious diseases (for up
to 1 month before or after any dose of ipilimumab)

- A history of prior treatment with ipilimumab or prior cluster of differentiation
(CD)137 agonist or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor or

- Concomitant therapy with any of the following: Interleukin (IL)-2,interferon, or
other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive
agents (over the counter [OTC]/herbal/prescribed); immunostimulant agents, other than
the study agent; other investigational therapies; or chronic use of systemic
corticosteroids (greater than prednisone 10 mg orally per day, or its equivalent)

- Prisoners or patients who are compulsorily detained (involuntarily incarcerated) for
treatment of either a psychiatric or physical (i.e., infectious) illness

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Fraction of patients who achieve an undetectable PSA (=< 0.2ng/ml)

Outcome Description:

Provided with the exact 95% confidence interval. PSA response as recommended by the Prostate Cancer Clinical Trials Working Group (PCWG2) definitions.

Outcome Time Frame:

Every 3 weeks for up to 12 weeks

Safety Issue:


Principal Investigator

Tom Beer, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

OHSU Knight Cancer Institute


United States: Food and Drug Administration

Study ID:




Start Date:

February 2012

Completion Date:

December 2015

Related Keywords:

  • Adenocarcinoma of the Prostate
  • Hormone-resistant Prostate Cancer
  • Recurrent Prostate Cancer
  • Stage IV Prostate Cancer
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Prostatic Neoplasms



OHSU Knight Cancer Institute Portland, Oregon  97239