Nivolumab and Ipilimumab Treatment in Prostate Cancer With an Immunogenic Signature

NCT03061539 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: CA209-935
• Study Type: interventional
• Target: 380
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective is to test the following hypothesis: Patients with metastatic castrate resistant prostate cancer that have progressed following at least one line of therapy and have an immunogenic signature will respond to combined PD-1 and CTLA4 inhibition.

Conditions

Prostate Cancer

Keywords

Immunogenic signature

Outcome Measures

Primary Outcomes (1)

• Composite response rate

  Patients will be considered as having had a treatment response if any one of the following criteria are satisfied: * Radiological response (RECIST 1.1) * PSA response ≥50% confirmed by a second PSA test at least 4 weeks later (PCWG3 2016) * Conversion of CTC count from ≥5 cells/7.5ml at baseline to \<5 cells/7.5ml confirmed by a second CTC test at least 4 weeks later (PCWG3 2016)

  Up to 5 years following the start of treatment

Secondary Outcomes (5)

• Overall survival

  From date of registration until the date of first documented date of death from any cause, assessed up to 5 years.

• Radiological progression free survival

  From registration to objective disease progression or death from any cause, whichever comes first, assessed up to 5 years

• PSA progression free survival

  From registration to PSA progression free survival assessed up to 5 years

• Change in patient reported outcome measures (NCI's PRO-CTCAE)

  From registration until 5 years post treatment

• Frequency and severity of adverse events

  For 24 months post the start of trial treatment

Study Arms (2)

Nivolumab & Ipilimumab - Cohort 1

EXPERIMENTAL

Patients will receive Nivolumab 1 mg/kg + ipilimumab 3 mg/kg every three weeks for a maximum of 4 doses followed by a 6 week gap after last combination dose. The patients will then receive 480 mg flat dose of nivolumab every 4 weeks for up to one year, or until progression, unacceptable toxicity or withdrawal of consent.

Drug: Nivolumab & Ipilimumab

Nivolumab & Ipilimumab - Cohort 2

EXPERIMENTAL

Patients will receive Nivolumab 3 mg/kg + ipilimumab 1 mg/kg every three weeks for a maximum of 4 doses followed by a 3 week gap after last combination dose. The patients will then receive 480 mg flat dose of nivolumab every 4 weeks for up to one year, or until progression, unacceptable toxicity or withdrawal of consent.

Drug: Nivolumab & Ipilimumab

Interventions

Nivolumab & Ipilimumab DRUG

Combination Therapy: Cohort 1: Nivolumab 1 mg/kg + ipilimumab 3 mg/kg every 3 weeks for a maximum of 4 cycles . Cohort 2 : Nivolumab 3mg/kg + ipilimumab 1mg/kg every 3 weeks for a maximum of 4 cycles. Treatment free gap after last combination dose : Cohort 1: 6 weeks; Cohort 2: 3 weeks Monotherapy: 480 mg flat dose of nivolumab every 4 weeks for up to 10 cycles, or until progression, unacceptable toxicity or withdrawal of consent

Nivolumab & Ipilimumab - Cohort 1; Nivolumab & Ipilimumab - Cohort 2

Eligibility Criteria

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

You may qualify if:

• Metastatic castrate resistant prostate cancer.
• Histologically confirmed prostate adenocarcinoma.
• Patient has archival prostate cancer tissue available or is willing to undergo a new biopsy.
• Immunogenic biomarker positive disease - see Appendix 1 NB patients will be included in the trial if they meet all other eligibility criteria. Analysis of the ImS will take place after registration. Patients who do not have ImS positive disease will be withdrawn from the trial.
• WHO performance status of 0-1.
• Adequate haematological status.
• Adequate liver and renal function.
• Has had 1 or more lines of systemic treatment for mCRPC.
• Documented prostate cancer progression within 6 months prior to screening
• Ongoing androgen deprivation with serum testosterone \<1.73 nmol/L.

You may not qualify if:

• Any history of autoimmune disease, with the exception of patients with a history of autoimmune-related hyperthyroidism or hypothyroidism who are in remission or on a stable dose of thyroid-replacement hormone.
• Patients with prior allogeneic stem cell or solid organ transplantation.
• Active invasive malignancy in the previous 2 years excluding non-melanoma skin cancer.
• History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e. bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan.
• (History of radiation pneumonitis in the radiation field is permitted).
• Patients with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.
• Patients with risk factors for bowel perforation.
• History of grade ≥2 peripheral neuropathy.
• Received therapeutic oral or intravenous (IV) antibiotics within 14 days prior to enrolment (Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or COPD) are eligible).
• Patients must not have had systemic corticosteroid therapy (\>10mg daily prednisone equivalent) for 14 days prior to study entry, or concomitant use of other immunosuppressive medications. The use of inhaled corticosteroids, physiologic replacement doses of glucocorticoids (i.e., for adrenal insufficiency), and mineralocorticoids (e.g., fludrocortisone) is allowed.
• Prior treatment with Sipuleucel-T, immune checkpoint targeting agents or other novel immune-oncology agents.
• Administration of a live, attenuated vaccine within 4 weeks prior to enrolment or anticipation that such a live, attenuated vaccine will be required during the study.
• Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 3 months prior to enrolment, unstable arrhythmias, or unstable angina.
• Patients with uncontrolled Type 1 diabetes mellitus. Patients controlled on a stable insulin regimen are eligible.
• Patients with uncontrolled adrenal insufficiency.

Sponsors & Collaborators

• University College, London: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

University College London Hospital

London, United Kingdom

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Nivolumab; Ipilimumab

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

Study Officials

• Dr Mark Linch

  University College London Hospitals

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Two-arm non-randomised, non-comparative phase II trial

Study Record Dates

• First Submitted: February 15, 2017
• First Posted: February 23, 2017
• Study Start: February 6, 2018
• Primary Completion: June 20, 2022
• Study Completion (Estimated): June 1, 2027
• Last Updated: September 28, 2022

Record last verified: 2022-06

Locations

GB (1)