Durvalumab With or Without Tremelimumab in Advanced Incurable Solid Malignancies Given With or Without Standard Chemotherapy Regimens

NCT02537418 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: I226
• Study Type: interventional
• Target: 153
• Locations: 1 country
• Sites: 7

Brief Summary

The purpose of this study is to find the highest dose of durvalumab or of durvalumab with tremelimumab that can be tolerated without causing very severe side effects when receiving standard chemotherapy and to see what effects the study drugs has on this type of cancer. Patients may receive durvalumab alone or in combination with tremelimumab.

Conditions

Solid Malignancies

Outcome Measures

Primary Outcomes (1)

• Confirm the recommended phase II dose (RP2D) of durvalumab ± tremelimumab in patients receiving standard chemotherapy

  24 months

Secondary Outcomes (3)

• Number of Participants with treatment-related adverse events as assessed by CTCAE v 4.0

  24 months

• Efficacy of durvalumab ± tremelimumab in patients receiving standard chemotherapy. Assessed by chest/abdomen/pelvis CT scan and other scans as necessary to document

  24 months

• Characterize the immunogenicity of durvalumab ± tremelimumab in patients receiving standard chemotherapy

  24 months

Study Arms (1)

durvalumab ± tremelimumab

EXPERIMENTAL

durvalumab; Day 1 every 3 weeks or 4 weeks tremelimumab; every 3-6 weeks for a total of 1-6 doses

Drug: durvalumab; Drug: tremelimumab

Interventions

durvalumab DRUG

durvalumab ± tremelimumab

tremelimumab DRUG

durvalumab ± tremelimumab

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 cancer that is advanced / metastatic / recurrent or unresectable and for which no curative therapy exists.
• Patients must be considered suitable candidates for and eligible to receive one of the regimens (including durvalumab and tremelimumab alone (dose level 5) included in this protocol and which is open to accrual. For each regimen, specific criteria for registration may be applicable to the cohort/dose level to ensure tolerability in the planned phase II or III trials. Centres must confirm that the planned cohort is open to accrual and whether there are any restrictions on tumour types prior to approaching patients.
• For etoposide/carboplatin regimen, patients must have untreated small cell lung cancer (SCLC).
• If a formalin fixed paraffin embedded tissue block (from their primary or metastatic tumour) is available, patients must have provided informed consent for the release of the block. All patients must have provided informed consent for correlative studies.
• 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). Patients ideally should have measurable disease.
• Patients must have an ECOG performance status of 0, 1, or 2 (0 or 1 for untreated SCLC enrolled to etoposide/carboplatin). Patients with PS 2 must be considered fit for first line cytotoxic or immune based therapy and discussed with CCTG prior to enrolment.
• Previous Therapy
• Cytotoxic Chemotherapy:
• All Cohorts Except Etoposide-Carboplatin:
• Patients should not have received prior chemotherapy for advanced disease. Exceptions may be made for selected patients and regimens. Patients planned for dose level 5 may have received one line or prior chemotherapy. Consult CCTG before approaching patients.
• Notes: Patients planned for cisplatin regimens should have received no more than 250mg mg/m2 prior to cisplatin.
• Etoposide-Carboplatin Cohort:
• For dose levels 0-3, patients with untreated SCLC must have received two cycles of their first etoposide carboplatin regimen prior to registration to that chemotherapy cohort. For dose level 4, SCLC patients planned for the etoposide/carboplatin cohort may not have had prior chemotherapy regimens and do not have to have their first two cycles of etoposide-platinum prior to study entry.
• Other Systemic Therapy:
• Patients may have received other prior therapies including immunotherapy, angiogenesis inhibitors, PARP inhibitors or signal transduction inhibitors. Patients who have received other treatment with PD-L1 / PD-1, CTLA4 or other antibodies must not have had intolerable toxicity or required steroids to manage toxicity.

You may not qualify if:

• Patients with a history of other malignancies requiring concurrent anticancer therapy.
• 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\* or a prior history of severe (grade 3 or 4) immune mediated toxicity from other immune therapy or grade ≥ 3 infusion reaction.
• \* NOTE: Intranasal/inhaled corticosteroids or systemic steroids that do not to exceed 10 mg/day of prednisone or equivalent dose of an alternative corticosteroid are permissible.
• Live attenuated vaccination administered within 30 days prior to registration.
• History of hypersensitivity to durvalumab or tremelimumab or any excipient. Patients who have received other treatment with PD-L1 / PD-1, CTLA4 or other antibodies must not have had intolerable toxicity or required steroids to manage toxicity.
• Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥ 470 msec in screening ECG measured using standard institutional method or history of familial long QT syndrome.
• 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. 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);

Sponsors & Collaborators

• Canadian Cancer Trials Group: lead
• AstraZeneca: collaborator

Study Sites (7)

Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

Location

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

Cancer Centre of Southeastern Ontario at Kingston

Kingston, Ontario, K7L 5P9, Canada

Location

Ottawa Hospital Research Institute

Ottawa, Ontario, K1H 8L6, Canada

Location

University Health Network

Toronto, Ontario, M5G 2M9, Canada

Location

CHUM - Hopital Notre-Dame

Montreal, Quebec, H2L 4M1, Canada

Location

Related Publications (1)

• Juergens RA, Hao D, Ellis PM, Tu D, Mates M, Kollmannsberger C, Bradbury PA, Tehfe M, Wheatley-Price P, Robinson A, Bebb G, Laskin J, Goffin J, Hilton J, Tomiak A, Hotte S, Goss GD, Brown-Walker P, Sun X, Tsao MS, Cabanero M, Gauthier I, Song X, Dennis PA, Seymour LK, Smoragiewicz M, Laurie SA. A phase IB study of durvalumab with or without tremelimumab and platinum-doublet chemotherapy in advanced solid tumours: Canadian Cancer Trials Group Study IND226. Lung Cancer. 2020 May;143:1-11. doi: 10.1016/j.lungcan.2020.02.016. Epub 2020 Feb 28.

  PMID: 32169783 RESULT

MeSH Terms

Interventions

durvalumab; tremelimumab

Study Officials

• Rosalyn Juergens

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

  STUDY CHAIR

• Desiree Hao

  Tom Baker Cancer Centre, Calgary, Alberta, Canada

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 27, 2015
• First Posted: September 1, 2015
• Study Start: October 16, 2015
• Primary Completion: July 20, 2018
• Study Completion (Estimated): December 31, 2026
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (7)