A Phase II Study of Durvalumab (MEDI4736) With or Without Tremelimumab in Patients With Metastatic Castration Resistant Prostate Cancer
Overview
- Phase
- Phase 2
- Intervention
- Durvalumab
- Conditions
- Prostate Cancer
- Sponsor
- Canadian Cancer Trials Group
- Enrollment
- 52
- Locations
- 11
- Primary Endpoint
- Objective Response Rate Measured by RECIST 1.1
- Status
- Completed
- Last Updated
- 11 months ago
Overview
Brief Summary
The purpose of this study is to find out the effects of giving durvalumab alone or in combination with tremelimumab on this type of cancer. In addition, this study will look at the side effects of durvalumab when given alone or in combination with tremelimumab.
Detailed Description
Durvalumab is a new type of drug for many types of cancer. Laboratory tests show that it works by allowing the immune system to detect cancer and stimulate the immune response. This may help to slow down the growth of cancer or may cause cancer cells to die. Durvalumab has been shown to shrink tumours in animals and has been studied in nearly 2000 people and seems promising but it is not clear if it can offer better results than standard treatment alone. Tremelimumab is a new type of drug for various types of cancers. It works in a similar way to durvalumab and may improve the effect of durvalumab. This may also help slow the growth of the cancer cells or may cause cancer cells to die. Tremelimumab has been shown to shrink tumours in animals and has been studied in nearly 1500 people and seems promising but it is not clear if it can offer better results than standard treatment alone when used with durvalumab Combinations of durvalumab and tremelimumab have also been studied and when combined have been shown to increase tumour shrinkage in animals compared to either drug alone. While the combination has been studied in 217 people, it is not clear if it can offer better results than standard treatment.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients must have histologically confirmed adenocarcinoma of the prostate that is castrate resistant.
- •Disease progression as defined as one or both of the following: PSA Progression: A rising PSA with 2 subsequent rises over a reference value (not necessarily consecutively), measured a minimum of one week apart. The PSA that confirms progression must have a value of ≥ 2 ng/ml (ug/L).
- •OR Objective Progression:
- •RECIST 1.1
- •PCWG 3 Criteria for bone progression
- •Patients must be surgically or medically castrated, with testosterone levels of \< 50 ng/dL (\< 1.7 nM). Patients who have not undergone orchiectomy must continue (or restart if previously discontinued) LHRH therapy throughout the study.
- •All patients must have a tumour block from their primary or metastatic tumour available and consent to release the block/recently cut slides for correlative analyses and the centre/pathologist must have agreed to the submission of the specimen(s). The site of planned biopsy must not be the measurable lesion.
- •Presence of clinically and/or radiologically documented disease. All radiology studies must be performed within 28 days prior to randomization (within 35 days if negative).
- •All patients must have at least one measurable lesion as defined by RECIST 1.1 that has not been the site of the protocol mandated biopsy. The criteria for defining measurable disease are as follows: CT scan (with slice thickness of 5 mm) ≥ 10 mm --\> longest diameter; Lymph nodes by CT scan ≥ 15 mm --\> measured in short axis
- •Patients must be ≥ 18 years of age.
Exclusion Criteria
- •Patients with a history of other malignancies requiring concurrent anticancer therapy.
- •Patients with brain metastases are not eligible.
- •Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease (e.g. colitis or Crohn's disease), diverticulitis with the exception of diverticulosis, celiac disease or other serious gastrointestinal chronic conditions associated with diarrhea), systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome (granulomatosis with polyangiitis), rheumatoid arthritis, hypophysitis, uveitis, etc., within the past 3 years prior to the start of treatment. The following are exceptions to this criterion:
- •Patients with alopecia.
- •Patients with Grave's disease, vitiligo or psoriasis not requiring systemic treatment (within the last 2 years).
- •Patients with hypothyroidism (e.g. following Hashimoto syndrome) stable on hormone replacement.
- •History of primary immunodeficiency, history of allogenic organ transplant that requires therapeutic immunosuppression and the use of immunosuppressive agents within 28 days of randomization or a prior history of severe (grade 3 or 4) immune mediated toxicity from other immune therapy or grade ≥ 3 infusion reaction.
- •Live attenuated vaccination administered within 30 days prior to randomization or within 30 days of receiving durvalumab.
- •History of hypersensitivity to durvalumab or tremelimumab or any excipient. Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab or an anti-CTLA4, including tremelimumab.
- •Patients who have experienced untreated and/or uncontrolled cardiovascular conditions and/or have symptomatic cardiac dysfunction (unstable angina, congestive heart failure, myocardial infarction within the previous year or cardiac ventricular arrhythmias requiring medication, history of 2nd or 3rd degree atrioventricular conduction defects). Patients with a significant cardiac history, even if controlled, should have a LVEF ≥ 50%.
Arms & Interventions
Arm A - Durvalumab plus Tremelimumab
Durvalumab-IV for 60 minutes day 1 every 4 weeks Tremelimumab-IV every 60 minutes day 1, cycles 1-4
Intervention: Durvalumab
Arm A - Durvalumab plus Tremelimumab
Durvalumab-IV for 60 minutes day 1 every 4 weeks Tremelimumab-IV every 60 minutes day 1, cycles 1-4
Intervention: Tremelimumab
Arm B - Durvalumab alone
Durvalumab-IV for 60 minutes day 1 every 4 weeks
Intervention: Durvalumab
Outcomes
Primary Outcomes
Objective Response Rate Measured by RECIST 1.1
Time Frame: 2 years
Response evaluated using the revised international criteria (1.1) proposed by the RECIST (Response Evaluation Criteria in Solid Tumours) for target and non-target lesions and assessed by CT or MRI: Complete Response (CR), disappearance of all target and non-target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions, or in the case of complete remission of the target lesions, when one or more non-target lesions can still be distinguished; Overall Response (OR) = CR + PR.
Objective Response Rate by iRECIST
Time Frame: 2 years
Response evaluated using iRECIST (modified Response Evaluation Criteria in Solid Tumours 1.1 for immune-based therapeutics) for target and non-target lesions and assessed by CT or MRI: Complete Response (CR), disappearance of all target and non-target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions, or in the case of complete remission of the target lesions, when one or more non-target lesions can still be distinguished; Overall Response (OR) = CR + PR.
Secondary Outcomes
- Time to Objective Disease Progression(2 years)
- Prostate-specific Antigen (PSA) Response Rate(2 years)