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

• ClinicalTrials.gov Identifier: NCT02870920
• Recruitment Status: Completed
• First Posted: August 17, 2016
• Results First Posted: January 19, 2021
• Last Update Posted: December 8, 2023
• Sponsor: Canadian Cancer Trials Group
• Collaborator: AstraZeneca
• Information provided by (Responsible Party): Canadian Cancer Trials Group

Tracking Information

• First Submitted Date: August 10, 2016
• First Posted Date: August 17, 2016
• Results First Submitted Date: November 20, 2020
• Results First Posted Date: January 19, 2021
• Last Update Posted Date: December 8, 2023
• Actual Study Start Date: October 12, 2016
• Actual Primary Completion Date: October 18, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 12, 2021)

Overall Survival [ Time Frame: 24 months ]

Time from randomization to death from any cause with patients who were alive at the time of the final analysis or who became lost to follow-up censored at their last date known to be alive.

• Original Primary Outcome Measures (submitted: August 12, 2016): Overall survival [ Time Frame: 24 months ]

Current Secondary Outcome Measures (submitted: January 12, 2021)

• Progression-free Survival [ Time Frame: 24 months ]
  Defined as the time from randomization to the first objective documentation of disease progression, defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions, or death due to any cause with patients who had not progressed or died at the time of final analysis censored on the date of the last tumour assessment.
• Objective Response Rate [ Time Frame: 24 months ]
  Defined as percentage of participants with objective response over all participants randomized. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Objective Response (OR) = CR + PR.

Original Secondary Outcome Measures (submitted: August 12, 2016)

• Progression-free survival defined as the time from randomization to the first objective documentation of disease progression or death due to any cause [ Time Frame: 24 months ]
• Objective response rate defined as the proportion of patients with a documented complete response and partial response based on RECIST 1.1 [ Time Frame: 24 months ]
• Number and severity of adverse events using the NCI Common Terminology Criteria for Adverse Events. [ Time Frame: 24 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Durvalumab and Tremelimumab and Best Supportive Care vs Best Supportive Care in Patients With Advanced Colorectal Cancer
• Official Title: A Phase II Randomized Study of Durvalumab and Tremelimumab and Best Supportive Care vs Best Supportive Care Alone in Patients With Advanced Colorectal Adenocarcinoma Refractory to Standard Therapies
• 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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Colorectal Cancer

Intervention

• Drug: Tremelimumab
• Drug: Durvalumab
  Other Name: Imfinzi
• Other: Best Supportive Care

Study Arms

• Active Comparator: Best Supportive Care
  Best supportive care available
  Intervention: Other: Best Supportive Care
• Experimental: 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
  Interventions:

  • Drug: Tremelimumab
  • Drug: Durvalumab
  • Other: Best Supportive Care

Publications *

• 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.
• 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

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 12, 2016): 180
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: June 7, 2022
• Actual Primary Completion Date: October 18, 2018 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada

Administrative Information

• NCT Number: NCT02870920
• Other Study ID Numbers: CO26
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Canadian Cancer Trials Group
• Original Responsible Party: Same as current
• Current Study Sponsor: Canadian Cancer Trials Group
• Original Study Sponsor: Same as current
• Collaborators: AstraZeneca

Investigators

• Study Chair: Eric Chen; Univ. Health Network-Princess Margaret Hospital, Toronto ON Canada

• PRS Account: Canadian Cancer Trials Group
• Verification Date: June 2022