Durvalumab and Tremelimumab and Best Supportive Care vs Best Supportive Care in Patients With Advanced Colorectal Cancer

NCT ID: NCT02870920

Last Updated: 2023-12-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 180 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-10-12
• Study Completion Date: 2022-06-07

Brief Summary

The standard or usual treatment for this disease is treatment with drugs and other treatments that may help to make a patient better or may improve their quality of life. This treatment is known as "best supportive care" (BSC). Although patients with best supportive care can feel better for some months, the cancer usually continues to grow.

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 reactivate 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 a few 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 a few 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 and while the combination has been studied in a few people, it is not clear if it can offer better results than standard treatment.

Conditions

Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Best Supportive Care

Best supportive care available

Group Type: ACTIVE_COMPARATOR

Best Supportive Care

Intervention Type: OTHER

Durvalumab plus Tremelimumab and Best Supportive Care

Tremelimumab 75mg IV 60 minutes Day 1, cycles 1-4 Durvalumab 1500mg IV 60 minutes Day 1 every 28 days. Plus best supportive care

Group Type: EXPERIMENTAL

Tremelimumab

Intervention Type: DRUG

Durvalumab

Intervention Type: DRUG

Best Supportive Care

Intervention Type: OTHER

Interventions

Tremelimumab

Intervention Type: DRUG

Durvalumab

Intervention Type: DRUG

Best Supportive Care

Intervention Type: OTHER

Other Intervention Names

Imfinzi

Eligibility Criteria

Inclusion Criteria

• Must have histologically or pathologically confirmed advanced (metastatic or locally advanced) colorectal cancer that is unresectable.
• Received a prior thymidylate synthase inhibitor (e.g. 5-fluorouracil (5-FU), capecitabine, raltitrexed, UFT) for metastatic disease or as adjuvant therapy. A thymidylate synthase inhibitor may have been given in combination with oxaliplatin or irinotecan.
• Received and failed an irinotecan -containing regimen (i.e. single-agent or in combination) for treatment of metastatic disease, OR relapsed within 6 months of completion of an irinotecan-containing adjuvant therapy, OR have documented unsuitability for an irinotecan-containing regimen.
• Received and failed an oxaliplatin-containing regimen (i.e. single-agent or in combination) for treatment of metastatic disease, OR relapsed within 6 months of completion of an oxaliplatin-containing adjuvant therapy OR have documented unsuitability for an oxaliplatin-containing regimen.
• For patients with colorectal cancer that is RAS-wild type:

Received and failed a cetuximab or panitumumab-containing regimen (i.e. single-agent or in combination) for treatment of metastatic disease OR have documented unsuitability for a cetuximab or panitumumab-containing regimen

• Patient prior treatment with VEGF targeting therapy, such as bevacizumab, aflibercept, ramucirumab, or regorafenib, is permitted but not mandatory. Reasons not used are to be documented.
• Patient prior treatment with TAS-102 (an agent composed of a combination of trifluorothymidine (FTD) and tipiracil hydrochloride (TPI)), is permitted but not mandatory.
• The only remaining standard available therapy as recommended by the Investigator, in consultation with the patient, is best supportive care.
• Must have presence of measurable or evaluable disease as defined by Response Evaluation Criteria in Solid Tumours (RECIST 1.1).
• Imaging investigations including CT/MRI of chest/abdomen/pelvis or other scans as necessary to document all sites of disease done within 28 days prior to randomization.
• Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life expectancy of ≥ 12 weeks at the time of study entry.
• Must be ≥ 18 years of age.
• Women/men of childbearing potential must have agreed to use a highly effective contraceptive method.
• Patient must consent to provision of, and investigator(s) must confirm adequacy of tissue, and confirm access to and agree to submit within 4 weeks of randomization to the CCTG Central Tumour Bank, a representative formalin fixed paraffin block of tumour tissue in order that the specific correlative marker assays may be conducted.
• Patient must consent to provision of samples of blood in order that the specific correlative marker assays
• Patient is able (i.e. sufficiently fluent) and willing to complete the quality of life questionnaires in either English or French.

Patients must be accessible for treatment and follow-up. Investigators must assure themselves the patients randomized on this trial will be available for complete documentation of the treatment, adverse events, and follow-up.

• In accordance with CCTG policy, protocol treatment is to begin within 2 working days of patient randomization.
• The patient is not receiving therapy in a concurrent clinical study and the patient agrees not to participate in other clinical studies during their participation in this trial while on study treatment.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: collaborator

Canadian Cancer Trials Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Eric Chen

Role: STUDY_CHAIR

Univ. Health Network-Princess Margaret Hospital, Toronto ON Canada

Locations

Tom Baker Cancer Centre

Calgary, Alberta, Canada

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, Canada

The Moncton Hospital

Moncton, New Brunswick, Canada

Dr. H. Bliss Murphy Cancer Centre

St. John's, Newfoundland and Labrador, Canada

QEII Health Sciences Centre

Halifax, Nova Scotia, Canada

Royal Victoria Regional Health Centre

Barrie, Ontario, Canada

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, Canada

Cancer Centre of Southeastern Ontario at Kingston

Kingston, Ontario, Canada

London Regional Cancer Program

London, Ontario, Canada

Ottawa Hospital Research Institute

Ottawa, Ontario, Canada

Algoma District Cancer Program

Sault Ste. Marie, Ontario, Canada

Odette Cancer Centre

Toronto, Ontario, Canada

University Health Network

Toronto, Ontario, Canada

Windsor Regional Cancer Centre

Windsor, Ontario, Canada

Hopital Charles LeMoyne

Greenfield Park, Quebec, Canada

Hopital de la Cite-de-la-Sante

Laval, Quebec, Canada

L'Hotel-Dieu de Levis

Lévis, Quebec, Canada

CHUM - Hopital Notre-Dame

Montreal, Quebec, Canada

The Jewish General Hospital

Montreal, Quebec, Canada

Centre Integre Universitaire De Sante Et De Services

Montreal, Quebec, Canada

CHUQ-Pavillon Hotel-Dieu de Quebec

Québec, Quebec, Canada

Centre hospitalier universitaire de Sherbrooke

Sherbrooke, Quebec, Canada

Centre hospitalier regional de Trois-Rivieres

Trois-Rivières, Quebec, Canada

Allan Blair Cancer Centre

Regina, Saskatchewan, Canada

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, Canada

Countries

Canada

References

Chen EX, Jonker DJ, Loree JM, Kennecke HF, Berry SR, Couture F, Ahmad CE, Goffin JR, Kavan P, Harb M, Colwell B, Samimi S, Samson B, Abbas T, Aucoin N, Aubin F, Koski SL, Wei AC, Magoski NM, Tu D, O'Callaghan CJ. Effect of Combined Immune Checkpoint Inhibition vs Best Supportive Care Alone in Patients With Advanced Colorectal Cancer: The Canadian Cancer Trials Group CO.26 Study. JAMA Oncol. 2020 Jun 1;6(6):831-838. doi: 10.1001/jamaoncol.2020.0910.

Reference Type: RESULT

PMID: 32379280 (View on PubMed)

Eric X. Chen, MD, PhD; Jonathan M. Loree, MD; Emma Titmuss, MSc; Derek J. Jonker, MD; Hagen F. Kennecke, MD; Scott Berry, MD; Felix Couture, MD; Chaudharry E. Ahmad, MD; John R. Goffin, MD; Petr Kavan, MD; Mohammed Harb, MD; Bruce Colwell, MD; Setareh Samimi, MD; Benoit Samson, MD; Tahir Abbas,MD; Nathalie Aucoin, MD; Francine Aubin, MD; Sheryl Koski, MD; Alice C.Wei, MD; Dongsheng Tu, PhD; Chris J. O'Callaghan, PhD

Reference Type: RESULT

Ma LX, Titmuss E, Loree JM, Jonker DJ, Kennecke HF, Berry S, Couture F, Ahmad CE, Goffin JR, Kavan P, Harb M, Colwell B, Samimi S, Samson B, Abbas T, Aucoin N, Aubin F, Koski S, Tu D, O'Callaghan C, Chen EX. Plasma arginine as a predictive biomarker for outcomes with immune checkpoint inhibition in metastatic colorectal cancer: a correlative analysis of the CCTG CO.26 trial. J Immunother Cancer. 2024 Dec 4;12(12):e010094. doi: 10.1136/jitc-2024-010094.

Reference Type: DERIVED

PMID: 39631846 (View on PubMed)

Topham JT, O'Callaghan CJ, Feilotter H, Kennecke HF, Lee YS, Li W, Banks KC, Quinn K, Renouf DJ, Jonker DJ, Tu D, Chen EX, Loree JM. Circulating Tumor DNA Identifies Diverse Landscape of Acquired Resistance to Anti-Epidermal Growth Factor Receptor Therapy in Metastatic Colorectal Cancer. J Clin Oncol. 2023 Jan 20;41(3):485-496. doi: 10.1200/JCO.22.00364. Epub 2022 Aug 25.

Reference Type: DERIVED

PMID: 36007218 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

CO26

Identifier Type: -

Identifier Source: org_study_id