A Phase II Study of Durvalumab Treatment - Substudy A: In Patients Who Discontinued Prior Checkpoint Therapy Due to Immune Related Toxicity - Substudy B: For Continued Treatment (+/- Tremelimumab) of Patients Previously Enrolled to Completed CCTG Studies

NCT03847649 | Recruiting Phase 2 DMC

• 1 other identifier: I238
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 12

Brief Summary

I238A: The purpose of this study is to find out what effects being treated with durvalumab has on cancer. The researchers doing this study also want to evaluate if prednisone (a type of steroid), when given together with durvalumab, can reduce any side effects. I238B: The purpose of this study is to allow patients previously enrolled on a completed CCTG trial to continue treatment with durvalumab (+/- tremelimumab)

Conditions

Cancer

Outcome Measures

Primary Outcomes (3)

• Substudy A: Number and severity of adverse events

  To determine the safety and toxicity profile of rechallenging with durvalumab in patients who previously discontinued immunotherapy due to irAE.

  2 years

• Substudy B: To facilitate continued treatment with durvalumab (+/- Tremelimumab) for patients currently enrolled on completed CCTG trials

  2 years

• Substudy B: Number and severity of adverse events

  2 years

Secondary Outcomes (3)

• Substudy A:Objective response rate RECIST 1.1

  2 years

• Substudy A: Objective response rate iRECIST

  2 years

• Substudy A: Efficacy of corticosteroids in preventing recurrent or new grade 2 or higher irAEs as estimated by the percentages of patients who received corticosteroids and developed recurrent or new grade 2 or higher irAEs

  2 years

Study Arms (3)

Cohort 1: High Risk

ACTIVE COMPARATOR

Drug: Durvalumab; Drug: Prednisone

Cohort 2: Standard Risk - Arm A

ACTIVE COMPARATOR

Drug: Durvalumab; Drug: Prednisone

Cohort 2: Standard Risk - Arm B

ACTIVE COMPARATOR

Drug: Durvalumab; Drug: Tremelimumab

Interventions

Durvalumab DRUG

1500 mg IV, 60 min, Day 1 every 4 weeks

Cohort 1: High Risk; Cohort 2: Standard Risk - Arm A; Cohort 2: Standard Risk - Arm B

Prednisone DRUG

0.5mg/kg; PO, Daily cycles 1 \& 2

Cohort 1: High Risk

Tremelimumab DRUG

Patients previously enrolled on a completed CCTG trial to continue treatment with durvalumab (+/- tremelimumab)

Cohort 2: Standard Risk - Arm B

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically and/or cytologically confirmed solid tumour, that is advanced/ metastatic/recurrent or unresectable and for which no curative therapy exists.
• Patients must live within Canada and have received durvalumab alone, or durvalumab in combination with tremelimumab, with or without chemotherapy/targeted therapy. Patients who have received other anti PD-1/PD-L1 agents +/- anti CTLA agents are eligible, providing full details of prior therapy, toxicity and management are available. Consult with CCTG for further details.
• Patients must have previously discontinued immunotherapy due to an irAE.
• Immune-related adverse events must have resolved to ≤ grade 1 or baseline and patient must have completed corticosteroid therapy at least 28 days prior to registration in this current study.
• Complete response, partial response or prolonged stable disease (SD ≥ 8 weeks) to initial immunotherapy. Patients that received prior adjuvant/neoadjuvant/consolidation immunotherapy are eligible providing there has been at least a 6 month treatment free interval prior to enrollment and patient has received at least one standard-of-care chemotherapy regimen in the palliative setting (discuss with CCTG if chemotherapy is not considered standard of care or not indicated or patient refused/not eligible as such patients are eligible).
• Patients must have a life expectancy of at least 12 weeks.
• Tumour material may have already been submitted to CCTG for the initial trial. If an additional formalin fixed paraffin embedded tissue block (from their primary or metastatic tumour) is available from tissue collected after immunotherapy discontinuation, patients must have provided informed consent for the release of the block. All patients must have provided informed consent for correlative studies. If patients from non-CCTG trials or commercial use are eventually enrolled, tumour material is also required if available, preferably from tissue collected after immunotherapy discontinuation.
• Presence of clinically and/or radiologically documented disease. All radiology studies must be performed within 28 days prior to enrollment (within 35 days if negative). Patients ideally should have measurable disease.
• ECOG performance status 0 or 1
• Previous Therapy
• Patients may have received prior cytotoxic chemotherapy following discontinuation of immunotherapy for irAE.
• Patients may have received other prior therapies such as tyrosine kinase inhibitors or other targeted agents, following discontinuation of immunotherapy for irAE.
• Patients may not have received subsequent immune checkpoint inhibitors (anti-PD-(L)1 and anti-CTLA-4) following discontinuation of immunotherapy for irAE. Vaccines and oncolytic viruses are permitted.
• Patients must have recovered from all reversible toxicity related to prior chemotherapy or systemic therapy (unless grade 1, irreversible, or considered by investigator as not clinically significant) and have adequate washout as follows: Longest of one of the following:
• Two weeks;

You may not qualify if:

• In general, patients with prior grade 4 non-hematological, non-endocrine immune-related adverse events are not eligible.
• History of primary immunodeficiency, history of allogenic organ transplant that requires therapeutic immunosuppression and the use of immunosuppressive agents within 28 days of enrollment.
• Live attenuated vaccination administered within 30 days prior to enrollment or within 30 days of receiving durvalumab.
• History of hypersensitivity to durvalumab or any excipient.
• Any immune-related adverse event that required biologic agents such as infliximab, or mycophenolate motefil to manage.
• Documented progressive disease (PD) while on initial immunotherapy. Exception: patients who had iUPD but continued on immunotherapy, and did not have documented iCPD within 8 weeks of discontinuing immunotherapy
• 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.
• 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.
• Untreated symptomatic brain metastases or brain metastases in whom radiation or surgery is indicated.
• Patients with diabetes mellitus are eligible but must be clinically stable on therapy (if applicable) and investigator and patient should be aware of the potential risk of immune mediated pancreatic toxicity and B cell destruction.
• Pregnant or lactating women

Sponsors & Collaborators

• Canadian Cancer Trials Group: lead
• AstraZeneca: collaborator

Study Sites (12)

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

RECRUITING

BCCA - Kelowna

Kelowna, British Columbia, V1Y 5L3, Canada

RECRUITING

BCCA - Vancouver

Vancouver, British Columbia, V5Z 4E6, Canada

RECRUITING

Regional Health Authority B, Zone 2

Saint John, New Brunswick, E2L 4L2, Canada

RECRUITING

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

RECRUITING

Waterloo Regional Health Network (WRHN)

Kitchener, Ontario, N2G 1G3, Canada

RECRUITING

Ottawa Hospital Research Institute

Ottawa, Ontario, K1H 8L6, Canada

RECRUITING

University Health Network

Toronto, Ontario, M5G 2M9, Canada

RECRUITING

Windsor Regional Cancer Centre

Windsor, Ontario, N8W 2X3, Canada

RECRUITING

CHUM-Centre Hospitalier de l'Universite de Montreal

Montreal, Quebec, H2X 3E4, Canada

RECRUITING

CHU de Quebec-Hopital l'Enfant-Jesus (HEJ)

Québec, Quebec, G1J 1Z4, Canada

RECRUITING

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, S7N 4H4, Canada

RECRUITING

MeSH Terms

Conditions

Neoplasms

Interventions

durvalumab; Prednisone; tremelimumab

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Peter Ellis

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

  STUDY CHAIR

• Sara K Taylor

  BCCA-Cancer Centre for the Southern Interior, Kelowna, BC Canada

  STUDY CHAIR

Central Study Contacts

Pierre-Olivier Gaudreau

CONTACT

613-533-6430; p-ogaudreau@ctg.queensu.ca

Study Design

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

Model Details: Cohort 1: High Risk - Receives Durvalumab plus Prednisone Cohort 2: Standard Risk - Randomize 1:1 * Arm A: Durvalumab plus prednisone * Arm B: Durvalumab (+/- tremelimumab) For BR34 pts only: Durvalumab (+/- Tremelimumab)

Study Record Dates

• First Submitted: February 19, 2019
• First Posted: February 20, 2019
• Study Start: March 9, 2020
• Primary Completion (Estimated): April 30, 2030
• Study Completion (Estimated): April 30, 2031
• Last Updated: June 11, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CA (12)