Durvalumab With or Without Tremelimumab in Metastatic Castration Resistant Prostate Cancer

NCT02788773 | Completed Phase 2 Results DMC

• 1 other identifier: I232
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 11

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.

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (2)

• Objective Response Rate Measured by RECIST 1.1

  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.

  2 years

• Objective Response Rate by iRECIST

  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.

  2 years

Secondary Outcomes (2)

• Prostate-specific Antigen (PSA) Response Rate

  2 years

• Time to Objective Disease Progression

  2 years

Study Arms (2)

Arm A - Durvalumab plus Tremelimumab

EXPERIMENTAL

Durvalumab-IV for 60 minutes day 1 every 4 weeks Tremelimumab-IV every 60 minutes day 1, cycles 1-4

Drug: Durvalumab; Drug: Tremelimumab

Arm B - Durvalumab alone

EXPERIMENTAL

Durvalumab-IV for 60 minutes day 1 every 4 weeks

Drug: Durvalumab

Interventions

Durvalumab DRUG

Arm A - Durvalumab plus Tremelimumab; Arm B - Durvalumab alone

Tremelimumab DRUG

Arm A - Durvalumab plus Tremelimumab

Eligibility Criteria

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

You may qualify if:

• 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.
• ECOG performance status 0 or 1.
• Prior Therapy
• Systemic Therapy:
• prior regimen of cytotoxic chemotherapy in the CRPC setting is permitted.
• Hormonal Therapy:

You may not qualify if:

• 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%.
• Concurrent treatment with other investigational drugs or anti-cancer therapy (except LHRH in patients not surgically castrated).
• Patients with serious illnesses or medical conditions which would not permit the patient to be managed according to the protocol (including corticosteroid administration), or would put the patient at risk. This includes but is not limited to:
• History of significant neurologic or psychiatric disorder which would impair the ability to obtain consent or limit compliance with study requirements.
• Active infection requiring systemic therapy; (including any patient known to have active hepatitis B, hepatitis C or human immunodeficiency virus (HIV) or tuberculosis or any infection requiring systemic therapy).
• Active peptic ulcer disease or gastritis.

Sponsors & Collaborators

• Canadian Cancer Trials Group: lead
• AstraZeneca: collaborator

Study Sites (11)

BCCA - Cancer Centre for the Southern Interior

Kelowna, British Columbia, V1Y 5L3, Canada

Location

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

Kingston Health Sciences Centre

Kingston, Ontario, K7L 2V7, Canada

Location

London Regional Cancer Program

London, Ontario, N6A 5W9, Canada

Location

Ottawa Hospital Research Institute

Ottawa, Ontario, K1H 8L6, Canada

Location

Odette Cancer Centre

Toronto, Ontario, M4N 3M5, Canada

Location

University Health Network

Toronto, Ontario, M5G 2M9, Canada

Location

Allan Blair Cancer Centre

Regina, Saskatchewan, S4T 7T1, Canada

Location

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, S7N 4H4, Canada

Location

Related Publications (1)

• Winquist E, Hotte SJ, Chi K, Sridhar S, Ellard S, Ong M, Iqbal N, Salim M, Emmenegger U, Gingerich JR, Lalani AK, Major P, Kollmannsberger C, Yip S, Hansen A, Finch D, Canil C, Hutchenreuther J, Vera-Badillo F, Smoragiewicz M, Cabanero M, Tsao MS, Ritch E, Wyatt AW, Seymour L. Randomized Phase II Study of Durvalumab with or without Tremelimumab in Patients with Metastatic Castration-Resistant Prostate Cancer. Clin Cancer Res. 2025 Jan 6;31(1):45-55. doi: 10.1158/1078-0432.CCR-24-1612.

  PMID: 39513948 RESULT

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

durvalumab; tremelimumab

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Lesley Seymour
• Organization: Canadian Cancer Trials Group

lseymour@ctg.queensu.ca

6135336430

Study Officials

• Sebastien Hotte

  Juravinski Cancer Centre at Hamilton Health Sciences, Hamilton, ON Canada

  STUDY CHAIR

• Eric W Winquist

  London Regional Cancer Program, London ON Canada

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 27, 2016
• First Posted: June 2, 2016
• Study Start: December 15, 2016
• Primary Completion: November 22, 2021
• Study Completion: May 1, 2025
• Last Updated: May 15, 2025
• Results First Posted: September 7, 2023

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CA (11)