Overview

Ipilimumab and GMCSF Immunotherapy for Prostate Cancer

Status:
Withdrawn
Trial end date:
2018-12-01
Target enrollment:
0
Participant gender:
Male
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.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Lawrence Fong
Collaborators:
Bristol-Myers Squibb
Sanofi
Treatments:
Antibodies, Monoclonal
Ipilimumab
Sargramostim
Criteria
Inclusion Criteria:

1. Histologically confirmed, metastatic prostate cancer (positive bone scan and/or
measurable disease on CT scan and/or MRI of the abdomen and pelvis).

2. 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

3. 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

4. Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2 and life expectancy
> 12 weeks.

5. At least 18 years of age or older.

6. Patients receiving any other hormonal therapy, including any dose of megestrol acetate
(Megace), Proscar (finasteride), any herbal product known to decrease PSA levels (e.g.
Saw Palmetto, PC-SPES), or any systemic corticosteroid, must discontinue the agent for
at least four weeks prior to study treatment. Progressive disease as defined above
must be documented after discontinuation of any hormonal therapy (with the exception
of a LHRH agonist or antagonist).

7. Prior radiation therapy must be completed > 4 weeks prior to enrollment and the
patient must be recovered from all toxicity. Prior radiopharmaceuticals (strontium,
samarium) must be completed ≥ 8 weeks prior to enrollment.

8. Because of the unknown potential risk to a gamete and/or developing embryo from this
investigational therapy, patients must agree to use adequate contraception (barrier
method for males) for the duration of study participation, and for three months after
discontinuing therapy.

Exclusion Criteria:

1. Prior chemotherapy for prostate cancer, with the exception of neoadjuvant
chemotherapy, because of the potential effect of chemotherapy on the immune system.

2. Prior investigational immunotherapy. Prior sipuleucel-T treatment is allowed but must
be completed at least 4 weeks prior to initiating treatment on this protocol.

3. 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.

4. 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

5. History or radiologic evidence of central nervous system metastases.

6. Medical or psychiatric illness that would preclude participation in the study or the
ability of patients to provide informed consent for themselves.

7. 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).

8. Concurrent or prior malignancy except for the following:

- Adequately treated basal or squamous cell skin cancer

- Adequately treated stage I or II cancer from which the patient is currently in
complete remission

- Any other cancer from which the patient has been disease-free for 5 years

9. HIV or other history of immunodeficiency disorder.

10. Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for
treatment of either a psychiatric or medical (e.g. infectious) illness.

11. 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 AEs, such as a condition associated with frequent diarrhea.

12. A history of prior treatment with ipilimumab or prior CD137 agonist or CTLA 4
inhibitor or agonist.