Prostate CancerPhase 2NCT01530984
Ipilimumab and GMCSF Immunotherapy for Prostate Cancer
A Phase 2 study testing Ipilimumab and GM-CSF in people with Prostate Cancer, run by Lawrence Fong at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- Ipilimumab and GM-CSF
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2015to Dec 2018
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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.
- 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).
- 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.
- 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.
Who cannot join
- 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
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- 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:
- 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
- HIV or other history of immunodeficiency disorder.
- Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or medical (e.g. infectious) illness.
- 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.
- A history of prior treatment with ipilimumab or prior CD137 agonist or CTLA 4 inhibitor or agonist.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California
San Francisco, California, 94115
About this study
Official title: Anti-CTLA4 Blockade Alone or Combined With Systemic GM-CSF for Prostate Cancer Immunotherapy
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.
Read the detailed description
Ipilimumab is an antibody (proteins that can find and destroy foreign molecules such as those on bacteria and viruses) against CTLA-4 (a molecule that controls a part of the immune system by shutting it down). It is approved by the U.S. Food and Drug Administration (FDA) to treat patients with late-stage melanoma, skin cancer. The use of ipilimumab in patients with CRPC has not been approved by the FDA.
Some patients in this study will receive GM-CSF along with ipilimumab. In clinical trials, GM-CSF has been safely given to prostate cancer patients in combination with ipilimumab. GM-CSF is not approved by the FDA for use as treatment for prostate cancer. Studies in patients with prostate cancer suggest that GM-CSF may activate the immune system. Since ipilimumab can help keep the immune system from turning off and allow an immune reaction to occur, and GM-CSF can increase the activity of the immune system, it is possible that they may work together to increase the immune response to cancer. The use of ipilimumab in combination with GM-CSF in patients with CRPC has not been approved by the FDA.
It is theorized that if antigen presentation could be improved, the immunostimulatory effects of CTLA-4 blockade could be augmented with improvements in clinical response. To that end, UCSF conducted a phase I clinical trial of ipilimumab in combination with GM-CSF, a cytokine that has been demonstrated to enhance the functional activities of effector cells, including dendritic cells (DC), neutrophils, and monocytes, in chemotherapy-naïve men with CRPC (Protocol 6032).32 Exposure to GM-CSF increases class II MHC expression on dendritic cells and is thought to lead to increased antigen presentation to T cells, stimulating T cell responses, although this mechanism has not been confirmed. We have extensively studied the effects of treatment demonstrating a dose-response relationship in the activation of CD4 and CD8 T cells. Moreover, the expansion of activated (CD25+CD69+) CD4 and CD8 T cells seen with this GM-CSF/ipilimumab combination trial was higher than that seen with GM-CSF or ipilimumab monotherapy seen in our other trials in prostate cancer patients.
We are proposing to conduct a non-comparative randomized phase II study of repetitive dosing of ipilimumab either alone or in combination with GM-CSF in patients with metastatic CRPC. The dosing interval for ipilimumab is based on the prior study which demonstrated drug levels ≥ 10 mg/mL (a minimum level required for CTLA-4 blockade in pre-clinical models) for greater than 28 days. Six doses of ipilimumab were chosen because six doses have been given safely in other trials. Maintenance dosing every three months is empirical, but this dosing frequency is based on discussions with Medarex, Inc. and Bristol-Meyers Squibb and is based on reports indicating the safety and potential efficacy of this maintenance regimen.
This study will use ipilimumab given every 28 days for six cycles (induction) followed by administration once every three months for patients who are not progressing (maintenance). A dosage of 10 mg/kg has been chosen based on the results to date of the phase I study. 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.
- Conditions
- Prostate Cancer
- Being tested
- Ipilimumab, GM-CSF
- Keywords
- prostate cancer, metastatic castrate resistant prostate cancer, Chemotherapy-naïve patients, Anti-CTLA4 blockade, systemic GM-CSF, Ipilimumab
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IpilimumabDrug
Also called CTLA-4 blockade
Ipilimumab 3 mg/kg on day 1 of a 28 day cycle for 6 cycles.
GM-CSFDrug
Also called Sargramostim
GM-CSF 250 mcg/m2 SQ on days 1-14 for 6 cycles.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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 Receives: Drug: Ipilimumab; Drug: GM-CSF |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2012 (estimated)
- Study startJun 2015
- Primary completionDec 2017 (estimated)
- Study completionDec 2018 (estimated)
Why it stopped: Unable to execute contract
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lawrence Fong
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb, Sanofi
- Responsible party
- Sponsor-investigator, Lawrence Fong, University of California, San Francisco
- Investigators
- Lawrence Fong, MD, Principal investigator, University of California, San FranciscoLawrence Fong, MD, Study chair, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01530984
- Sponsor's protocol ID
- CC# 12552
- Status last verified
- Oct 2015
- First submitted
- 7 Feb 2012
- Last updated
- 5 Oct 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Anti-CTLA4 Blockade Alone or Combined With Systemic GM-CSF for Prostate Cancer Immunotherapy
- ClinicalTrials.gov ID
- NCT01530984
- Acronym / sponsor ID
- CC# 12552
- Conditions
- Prostate Cancer
- Keywords
- prostate cancer, metastatic castrate resistant prostate cancer, Chemotherapy-naïve patients, Anti-CTLA4 blockade, systemic GM-CSF, Ipilimumab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Unable to execute contract
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Lawrence FongUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb, Sanofi
- Study start
- Jun 2015
- Primary completion
- Dec 2017 (estimated)
- Study completion
- Dec 2018 (estimated)
- First posted
- 10 Feb 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Ipilimumab is an antibody (proteins that can find and destroy foreign molecules such as those on bacteria and viruses) against CTLA-4 (a molecule that controls a part of the immune system by shutting it down). It is approved by the U.S. Food and Drug Administration (FDA) to treat patients with late-stage melanoma, skin cancer. The use of ipilimumab in patients with CRPC has not been approved by the FDA.
Some patients in this study will receive GM-CSF along with ipilimumab. In clinical trials, GM-CSF has been safely given to prostate cancer patients in combination with ipilimumab. GM-CSF is not approved by the FDA for use as treatment for prostate cancer. Studies in patients with prostate cancer suggest that GM-CSF may activate the immune system. Since ipilimumab can help keep the immune system from turning off and allow an immune reaction to occur, and GM-CSF can increase the activity of the immune system, it is possible that they may work together to increase the immune response to cancer. The use of ipilimumab in combination with GM-CSF in patients with CRPC has not been approved by the FDA.
It is theorized that if antigen presentation could be improved, the immunostimulatory effects of CTLA-4 blockade could be augmented with improvements in clinical response. To that end, UCSF conducted a phase I clinical trial of ipilimumab in combination with GM-CSF, a cytokine that has been demonstrated to enhance the functional activities of effector cells, including dendritic cells (DC), neutrophils, and monocytes, in chemotherapy-naïve men with CRPC (Protocol 6032).32 Exposure to GM-CSF increases class II MHC expression on dendritic cells and is thought to lead to increased antigen presentation to T cells, stimulating T cell responses, although this mechanism has not been confirmed. We have extensively studied the effects of treatment demonstrating a dose-response relationship in the activation of CD4 and CD8 T cells. Moreover, the expansion of activated (CD25+CD69+) CD4 and CD8 T cells seen with this GM-CSF/ipilimumab combination trial was higher than that seen with GM-CSF or ipilimumab monotherapy seen in our other trials in prostate cancer patients.
We are proposing to conduct a non-comparative randomized phase II study of repetitive dosing of ipilimumab either alone or in combination with GM-CSF in patients with metastatic CRPC. The dosing interval for ipilimumab is based on the prior study which demonstrated drug levels ≥ 10 mg/mL (a minimum level required for CTLA-4 blockade in pre-clinical models) for greater than 28 days. Six doses of ipilimumab were chosen because six doses have been given safely in other trials. Maintenance dosing every three months is empirical, but this dosing frequency is based on discussions with Medarex, Inc. and Bristol-Meyers Squibb and is based on reports indicating the safety and potential efficacy of this maintenance regimen.
This study will use ipilimumab given every 28 days for six cycles (induction) followed by administration once every three months for patients who are not progressing (maintenance). A dosage of 10 mg/kg has been chosen based on the results to date of the phase I study. 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ipilimumab alone | Experimental | Drug: IpilimumabIpilimumab 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). |
| Ipilimumab with GM-CSF | Experimental | Drug: Ipilimumab, Drug: GM-CSFIpilimumab 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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:
- Laboratory requirements:
- Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2 and life expectancy > 12 weeks.
- At least 18 years of age or older.
Key exclusion criteria (22 listed)
- 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:
- History or radiologic evidence of central nervous system metastases.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IpilimumabAlso: CTLA-4 blockadeIpilimumab 3 mg/kg on day 1 of a 28 day cycle for 6 cycles. | Drug | Ipilimumab alone, Ipilimumab with GM-CSF |
| GM-CSFAlso: SargramostimGM-CSF 250 mcg/m2 SQ on days 1-14 for 6 cycles. | Drug | Ipilimumab with GM-CSF |
Primary outcome
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.
Time frame: 12 weeks
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.
1 secondary outcome
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.
Time frame: 12 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lawrence Fong, MD principal investigator
University of California, San Francisco
Lawrence Fong, MD study chair
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ipilimumab and GM-CSF in people with Prostate Cancer, run by Lawrence Fong at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 5 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2015.