Ipilimumab and GMCSF Immunotherapy for Prostate Cancer

NCT01530984 | Withdrawn Phase 2 DMC

• 1 other identifier: CC# 12552
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label randomized phase II study. Patients are randomized so as to achieve uniform patient cohorts treated on each regimen. Twenty-seven patients will be required per treatment arm, and a total of 54 prostate cancer patients will be required to complete this study. The study will assess for clinical activity by Prostate Specific Antigen (PSA) response, of both single agent ipilimumab and the combination of GM-CSF and ipilimumab in chemotherapy-naïve patients with metastatic castrate resistant prostate cancer.

Conditions

Prostate Cancer

Keywords

prostate cancer; metastatic castrate resistant prostate cancer; Chemotherapy-naïve patients; Anti-CTLA4 blockade; systemic GM-CSF; Ipilimumab

Outcome Measures

Primary Outcomes (1)

• To assess for clinical activity by PSA response, of both single agent ipilimumab and the combination of GM-CSF and ipilimumab in chemotherapy-naïve patients with metastatic castrate resistant prostate cancer.

  To assess for clinical activity by PSA (prostate-specific antigen) decline of both single agent ipilimumab in chemotherapy-naïve patients with metastatic castrate resistant prostate cancer (CRPC). The primary endpoint is the proportion of treated patients achieving a \>30% decline in PSA.

  12 weeks

Secondary Outcomes (1)

• To evaluate the duration of PSA response and time to PSA progression. To quantify the frequency of immune toxicities. To evaluate T cell activation. To assess for clinical activity by objective response.

  12 weeks

Other Outcomes (2)

• Assessment of circulating tumor cell (CTC) frequency

  12 weeks

• Assessment of the antigen specific immune responses induced with treatment

  12 weeks

Study Arms (2)

Ipilimumab alone

EXPERIMENTAL

Ipilimumab 3 mg/kg (IV) will be given every 28 days for six cycles (induction) followed by administration once every three months for patients who are not progressing (maintenance).

Drug: Ipilimumab

Ipilimumab with GM-CSF

EXPERIMENTAL

Ipilimumab 3 mg/kg (IV) will be given every 28 days for six cycles (induction) followed by administration once every three months for patients who are not progressing (maintenance). GM-CSF 250 mcg/m2 SQ will be administered on days 1-14 in Cycles 1-6 and then every 3 months for 14 days beginning on the day of ipilimumab administration during the maintenance therapy phase

Drug: Ipilimumab; Drug: GM-CSF

Interventions

Ipilimumab DRUG

Ipilimumab 3 mg/kg on day 1 of a 28 day cycle for 6 cycles.

Also known as: CTLA-4 blockade

Ipilimumab alone; Ipilimumab with GM-CSF

GM-CSF DRUG

GM-CSF 250 mcg/m2 SQ on days 1-14 for 6 cycles.

Also known as: Sargramostim

Ipilimumab with GM-CSF

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed, metastatic prostate cancer (positive bone scan and/or measurable disease on CT scan and/or MRI of the abdomen and pelvis).
• Progressive disease after androgen deprivation, as defined by PSA Working Group 237 and/or RECIST criteria.38 Patients must have disease progression by one or both of the following:
• For patients with measurable disease, progression is defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions or the appearance of one or more new lesions, as per RECIST criteria version 1.1
• For patients with no measurable disease, a positive bone scan and elevated PSA will be required. PSA evidence for progressive prostate cancer consists of a PSA level of at least 2 ng/ml, which has risen on at least 2 successive occasions, at least 1 week apart. If the confirmatory PSA (#3) value is not greater (i.e., #3b) than the screening PSA (#2) value, then an additional test for rising PSA (#4) will be required to document progression
• If no prior orchiectomy has been performed, patients must remain on LHRH agonist or antagonist therapy. Patients who are receiving an antiandrogen as part of primary androgen ablation must demonstrate disease progression following discontinuation of the antiandrogen, defined as two consecutive rising PSA values, obtained at least two weeks apart, or documented osseous or soft tissue progression. At least one of the PSA values must be obtained at least four weeks (flutamide) or six weeks (bicalutamide or nilutamide) after discontinuation
• Laboratory requirements:
• Absolute neutrophil count (ANC) ≥ 1500/μL
• Bilirubin \< 1.5 x ULN
• Hemoglobin ≥ 8 g/dL
• PSA ≥ 2 ng/mL
• Platelets \> 100,000/μL
• AST and ALT \< 2.5 x ULN
• Creatinine clearance ≥ 60mL/min by the Cockcroft Gault equation Testosterone \< 50 ng/dL
• Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2 and life expectancy \> 12 weeks.
• At least 18 years of age or older.

You may not qualify if:

• Prior chemotherapy for prostate cancer, with the exception of neoadjuvant chemotherapy, because of the potential effect of chemotherapy on the immune system.
• Prior investigational immunotherapy. Prior sipuleucel-T treatment is allowed but must be completed at least 4 weeks prior to initiating treatment on this protocol.
• Current treatment with systemic steroid therapy (inhaled/topical steroids are acceptable). Systemic corticosteroids must be discontinued for at least 4 weeks prior to first treatment.
• History of autoimmune disease including, but not limited to:
• Systemic lupus erythematosis (SLE), scleroderma, CREST syndrome, rheumatoid arthritis
• Inflammatory bowel disease, celiac disease, primary biliary cirrhosis, autoimmune hepatitis
• Dermatomyositis, polymyositis, giant cell arteritis
• Autoimmune hemolytic anemia (AIHA), cryoglobulinemia, antiphospholipid antibody syndrome (APLS)
• Diabetes mellitus type I, myasthenia gravis, Grave's disease
• Wegener's granulomatosis or other vasculitis
• A history of Hashimoto's thyroiditis, psoriasis, or eczema, any of which has been inactive for at least one year, or isolated Raynaud's phenomenon is acceptable
• History or radiologic evidence of central nervous system metastases.
• Medical or psychiatric illness that would preclude participation in the study or the ability of patients to provide informed consent for themselves.
• Cardiovascular disease that meets one of the following: congestive heart failure (New York Heart Association Class III or IV), active angina pectoris, or recent myocardial infarction (within the last 6 months).
• Concurrent or prior malignancy except for the following:

Sponsors & Collaborators

• Lawrence Fong: lead
• Bristol-Myers Squibb: collaborator
• Sanofi: collaborator

Study Sites (1)

University of California

San Francisco, California, 94115, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Ipilimumab; Granulocyte-Macrophage Colony-Stimulating Factor; sargramostim

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors

Study Officials

• Lawrence Fong, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Lawrence Fong, MD

  University of California, San Francisco

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor in Residence

Study Record Dates

• First Submitted: February 7, 2012
• First Posted: February 10, 2012
• Study Start: June 1, 2015
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2018
• Last Updated: October 5, 2015

Record last verified: 2015-10

Locations

US (1)