Clinical trial NCT02870920: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer
Lead sponsor: Canadian Cancer Trials Group
Sponsor class: NETWORK
Collaborators: name: AstraZeneca
First posted: 2016-08-17
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Overall Survival
timeFrame: 24 months
Secondary outcomes:
measure: Progression-free Survival
timeFrame: 24 months
measure: Objective Response Rate
timeFrame: 24 months
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Vancouver
country: Canada
facility: BCCA - Vancouver Cancer Centre
state: British Columbia
city: Moncton
country: Canada
facility: The Moncton Hospital
state: New Brunswick
city: St. John's
country: Canada
facility: Dr. H. Bliss Murphy Cancer Centre
state: Newfoundland and Labrador
city: Halifax
country: Canada
facility: QEII Health Sciences Centre
state: Nova Scotia
city: Barrie
country: Canada
facility: Royal Victoria Regional Health Centre
state: Ontario
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre at Hamilton Health Sciences
state: Ontario
city: Kingston
country: Canada
facility: Cancer Centre of Southeastern Ontario at Kingston
state: Ontario
city: London
country: Canada
facility: London Regional Cancer Program
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital Research Institute
state: Ontario
city: Sault Ste. Marie
country: Canada
facility: Algoma District Cancer Program
state: Ontario
city: Toronto
country: Canada
facility: Odette Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
city: Windsor
country: Canada
facility: Windsor Regional Cancer Centre
state: Ontario
city: Greenfield Park
country: Canada
facility: Hopital Charles LeMoyne
state: Quebec
city: Laval
country: Canada
facility: Hopital de la Cite-de-la-Sante
state: Quebec
city: Levis
country: Canada
facility: L'Hotel-Dieu de Levis
state: Quebec
city: Montreal
country: Canada
facility: CHUM - Hopital Notre-Dame
state: Quebec
city: Montreal
country: Canada
facility: The Jewish General Hospital
state: Quebec
city: Montreal
country: Canada
facility: Centre Integre Universitaire De Sante Et De Services
state: Quebec
city: Quebec City
country: Canada
facility: CHUQ-Pavillon Hotel-Dieu de Quebec
state: Quebec
city: Sherbrooke
country: Canada
facility: Centre hospitalier universitaire de Sherbrooke
state: Quebec
city: Trois-Rivieres
country: Canada
facility: Centre hospitalier regional de Trois-Rivieres
state: Quebec
city: Regina
country: Canada
facility: Allan Blair Cancer Centre
state: Saskatchewan
city: Saskatoon
country: Canada
facility: Saskatoon Cancer Centre
state: Saskatchewan
Study officials:
affiliation: Univ. Health Network-Princess Margaret Hospital, Toronto ON Canada
name: Eric Chen
role: STUDY_CHAIR
References:
citation: 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.
citation: 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