Durvalumab and Tremelimumab in Patients With Advanced Rare Tumours

A Phase II Study of Durvalumab and Tremelimumab in Patients With Advanced Rare Tumours

The standard or usual treatment for this disease may be chemotherapy or other types of treatment to slow the spread of the disease and relieve some symptoms of this cancer.

Study Overview

• Status: Completed
• Conditions: Advanced Rare Tumours
• Intervention / Treatment: Drug: Durvalumab; Drug: 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 5000 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 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 250 people, it is not clear if it can offer better results than standard treatment.

• Study Type: Interventional
• Enrollment (Actual): 140
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 5L3
      • BCCA - Cancer Centre for the Southern Interior
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • BCCA - Vancouver Cancer Centre
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • CancerCare Manitoba
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • QEII Health Sciences Centre
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Juravinski Cancer Centre at Hamilton Health Sciences
    • London, Ontario, Canada, N6A 5W9
      • London Regional Cancer Program
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Hospital Research Institute
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network
  • Quebec
    • Montreal, Quebec, Canada, H2X 3E4
      • CHUM-Centre Hospitalier de l'Universite de Montreal
    • Montreal, Quebec, Canada, H4A 3J1
      • The Research Institute of the McGill University
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • Allan Blair Cancer Centre
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Saskatoon Cancer Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients must have histologically and/or cytologically confirmed cancer that is advanced / metastatic / recurrent or unresectable and for which no curative therapy exists as follows:

  1. Salivary carcinoma (excluding adenoid cystic carcinoma histology)
  2. Carcinoma of unknown primary with tumour infiltrating lymphocytes (TILs) and/or expressing PD-L1
  3. Mucosal melanoma
  4. Acral melanoma
  5. Osteosarcoma
  6. Undifferentiated pleomorphic sarcoma
  7. Clear cell carcinoma of the ovary
  8. Squamous cell carcinoma of the anal canal (SCCA)
• All patients must have a tumour tissue from their primary or metastatic tumour available
• Presence of clinically and/or radiologically documented disease. All radiology studies must be performed within 28 days prior to registration (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 ≥ 16 years of age.
• Patients must have an ECOG performance status of 0 or 1.
• Previous Therapy

Cytotoxic Chemotherapy:

Patients may have received prior chemotherapy - no limit on number of prior regimens.

Other Systemic Therapy:

Patients may have received other prior therapies including, angiogenesis inhibitors, PARP inhibitors or signal transduction inhibitors (tyrosine kinase inhibitors). Prior therapy with PD-1/PD-L1 or CTLA-4 inhibitors is not allowed.

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
• 5 half-lives for investigational agents
• Standard cycle length of standard therapies

Radiation:

Prior external beam radiation is permitted provided a minimum of 28 days (4 weeks) have elapsed between the last dose of radiation and date of registration. Exceptions may be made for low-dose, non-myelosuppressive radiotherapy after consultation with CCTG senior investigator. Concurrent radiotherapy is not permitted. Patients planned for concurrent chemotherapy-radiation are not eligible.

Surgery:

Previous surgery is permitted provided that a minimum of 28 days (4 weeks) have elapsed between any major surgery and date of registration, and that wound healing has occurred.

• Lab Requirements:

Absolute neutrophils ≥ 1.5 x 10^9/L Platelets ≥ 100 x 10^9/L Hemoglobin ≥ 90 g/L Bilirubin ≤ 1.5 x ULN (upper limit of normal)* AST and ALT ≤ 2.5 x ULN (if liver metastases are present, ≤ 5 x ULN) Serum creatinine < 1.25 x ULN or: Creatinine clearance ≥ 40 mLs/min

• Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements
• Women/men of childbearing potential must have agreed to use a highly effective contraceptive method.
• Patients must be accessible for treatment and follow up. Patients registered on this trial must be treated and followed at the participating centre.
• Subjects should not donate blood while participating in this study, or for at least 90 days following the last infusion of durvalumab or tremelimumab.
• In accordance with CCTG policy, protocol treatment is to begin within 2 working days of patient registration

Exclusion Criteria:

• Patients with a history of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other cancers curatively treated with no evidence of disease for ≥ 5 years.

• 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 registration.
• Live attenuated vaccination administered within 30 days prior to registration.
• 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%.
• Untreated symptomatic brain metastases or brain metastases in whom radiation or surgery is indicated.
• 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 (incl 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.
  • Known pneumonitis or pulmonary fibrosis with clinically significant impairment of pulmonary function.
• Pregnant or lactating women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Durvalumab + Tremelimumab; Durvalumab 1500 mg IV 60 min Day 1 every 4 weeks Tremelimumab 75 mg IV 60 min Day 1, cycles 1-4	Drug: Durvalumab; Drug: Tremelimumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate Measured by RECIST Version 1.1	Objective response rate is defined as the proportion of response evaluable patients who had complete response (CR) or partial response (PR) as their best response as assessed by RECIST version 1.1 criteria (i.e. a 30% decrease in the sum of the longest diameters of the target lesions maintained for at least 4 weeks (CR), or complete disappearance of disease and cancer related symptoms, also maintained for at least 4 weeks (CR)).	48 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Progression Based on Kaplan-Meier Method	defined as time from the date of randomization to the date of progression	48 months
Progression Free Survival Based on Kaplan-Meier Method	defined as time from the date of randomization to the date of progression or death	48 months

Collaborators and Investigators

• Sponsor: Canadian Cancer Trials Group
• Collaborators: AstraZeneca
• Investigators: Study Chair: Abha Gupta, Hospital for Sick Children, Toronto ON Canada

Publications and helpful links

General Publications

• Gupta AA, Tinker A, Jonker D, Jamal R, Hirte H, Winquist EW, Chu Q, Kollmannsberger C, Wong R, Alcindor T, Nielsen TO, Tsao M, Cottrell TR, Provencher D, Hilton J, Krzyzanowska MK, Elser C, Hotte S, Sederias J, Zhang S, Tu W, Dancey J. Durvalumab and tremelimumab in patients with advanced rare cancer: a multi-centre, non-blinded, open-label phase II basket trial. EClinicalMedicine. 2024 Dec 10;79:102991. doi: 10.1016/j.eclinm.2024.102991. eCollection 2025 Jan.

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2016
• Primary Completion (Actual): June 20, 2021
• Study Completion (Actual): January 29, 2025

Study Registration Dates

• First Submitted: August 22, 2016
• First Submitted That Met QC Criteria: August 22, 2016
• First Posted (Estimated): August 25, 2016

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 14, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Antineoplastic Agents, Immunological; Antineoplastic Agents; Durvalumab; Tremelimumab
• Other Study ID Numbers: I228

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No