BBI608 and Best Supportive Care vs Placebo and Best Supportive Care in Pretreated Advanced Colorectal Carcinoma

Colorectal Carcinoma Clinical Trial

Official title:

A Phase III Randomized Study of BBI608 and Best Supportive Care Versus Placebo and Best Supportive Care in Patients With Pretreated Advanced Colorectal Carcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01830621
• Other study ID #: CO23
• Status: Completed
• Phase: Phase 3
• Start date: May 10, 2013
• Est. completion date: May 16, 2016

Study information

• Verified date: August 2023
• Source: Canadian Cancer Trials Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to find out whether it is better to receive a new drug, BBI608, or better to receive no further treatment for colon or rectal cancer. To do this, half of the patients in this study will get BBI608 and the other half will receive a placebo (a substance that is designed not to do anything).

Description:

This research is being done because currently there are no approved remaining effective treatments for colon or rectal cancer.

The purpose of this study is to compare the effects on colon cancer of a new drug, BBI608, and best supportive care (BSC) compared to BSC alone.

BBI608 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 the usual care which is best supportive care alone.

The standard or usual treatment for this disease is treatment with drugs and other treatments that may help to make a patient feel 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 282
• Est. completion date: May 16, 2016
• Est. primary completion date: May 7, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically confirmed 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.

• 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 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 K-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

• The only remaining standard available therapy as recommended by the Investigator is best supportive care.

• Must have presence of measurable 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 14 days prior to randomization.

• Must have an ECOG Performance Status of 0 or 1.

• Must be = 18 years of age.

• For male or female patient of child producing potential: Must agree to use contraception or take measures to avoid pregnancy during the study and for 30 days after the last Protocol treatment dose.

• Women of child bearing potential (WOCBP) must have a negative serum or urine pregnancy test within 72 hours prior to randomization.

• Must have alanine transaminase (ALT) = 3 × institutional upper limit of normal (ULN) [= 5 × ULN in presence of liver metastases] within 14 days prior to randomization.

• Must have hemoglobin (Hgb) = 80 g/L within 14 days prior to randomization.

• Must have total bilirubin = 1.5 × institutional ULN [= 2.0 x ULN in presence of liver metastases] within 14 days prior to randomization.

• Must have creatinine = 1.5 × institutional ULN or Creatinine Clearance > 50 ml/min within 14 days prior to randomization.

• Must have absolute neutrophil count = 1.5 x 109/L within 14 days prior to randomization.

• Must have platelet count = 75 x 109/L within 14 days prior to randomization.

• Other biochemistry which must be done within 14 days prior to randomization includes lactate dehydrogenase (LDH) and alkaline phosphatase.

• Patient must consent to provision of, and investigator(s) must confirm access to and agree to submit at the request of the NCIC CTG 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 a sample of blood in order that the specific correlative marker assays may be conducted.

• Patient is able (i.e. sufficiently fluent) and willing to complete the Quality of Life and Health Utilities questionnaires in one of the validated languages for the questionnaires.

• Patients must be accessible for treatment and follow-up. Patients registered on this trial must be treated and followed at the participating centre. This implies there must be reasonable geographical limits placed on patients being considered for this trial.

• 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.

Exclusion Criteria:

• Anti-cancer chemotherapy or biologic therapy within the lesser of i) 21 days, or ii) the usual cycle length of the regimen (e.g. 14 days for FOLFOX), prior to the first planned dose of BBI608/placebo. An exception is made for capecitabine and regorafenib, where a minimum of 10 days since last dose must be observed prior to the first planned dose of BBI608/placebo.

• Radiotherapy, immunotherapy, or investigational agents within four weeks of first planned dose of BBI608/placebo, with the exception of a single dose of radiation up to 8 Gray (equal to 800 RAD) with palliative intent for pain control up to 14 days before randomization.

• Major surgery within 4 weeks prior to randomization.

• Any known symptomatic brain metastases requiring steroids.

• Women who are pregnant or breastfeeding.

• Gastrointestinal disorder(s) which, in the opinion of the Qualified/Principal Investigator, would significantly impede the absorption of an oral agent (e.g. active Crohn's disease, ulcerative colitis, extensive gastric and small intestine resection).

• Unable or unwilling to swallow BBI608/placebo capsules daily.

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, clinically significant non-healing or healing wounds, symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmia, significant pulmonary disease (shortness of breath at rest or mild exertion), uncontrolled infection or psychiatric illness/social situations that would limit compliance with study requirements.

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

• Prior treatment with BBI608.

• Any active disease condition which would render the protocol treatment dangerous or impair the ability of the patient to receive protocol therapy.

• Any condition (e.g. psychological, geographical, etc.) that does not permit compliance with the protocol.

Related Conditions & MeSH terms

• Carcinoma
• Colorectal Carcinoma
• Colorectal Neoplasms

Intervention

Drug:
• BBI608

• Placebo

Other:
• Best Supportive Care

Locations

Country	Name	City	State
Australia	Bankstown/ Lidcombe	Bankstown	New South Wales
Australia	Flinders Medical Centre	Bedford Park	South Australia
Australia	St John of God Bunbury Hospital	Bunbury
Australia	Townsville Hospital	Douglas	Queensland
Australia	Peter MacCallum Cancer Institute	East Melbourne	Victoria
Australia	Lyell McEwin Hospital	Elizabeth Vale	South Australia
Australia	Royal Hobart Hospital	Hobart	Tasmania
Australia	St John of God - Subiaco	Subiaco	Western Australia
Australia	The Queen Elizabeth Hospital	Woodville South	South Australia
Canada	BCCA - Abbotsford Centre	Abbotsford	British Columbia
Canada	The Royal Victoria Hospital	Barrie	Ontario
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Horizon Health Network,	Fredericton	New Brunswick
Canada	QEII Health Sciences Centre	Halifax	Nova Scotia
Canada	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario
Canada	BCCA - Cancer Centre for the Southern Interior	Kelowna	British Columbia
Canada	Hopital de la Cite-de-la-Sante	Laval	Quebec
Canada	L'Hotel-Dieu de Levis	Levis	Quebec
Canada	London Regional Cancer Program	London	Ontario
Canada	Credit Valley Hospital	Mississauga	Ontario
Canada	The Moncton Hospital	Moncton	New Brunswick
Canada	The Vitalite Health Network - Dr. Leon Richard	Moncton	New Brunswick
Canada	CHUM - Hopital Notre-Dame	Montreal	Quebec
Canada	McGill University - Dept. Oncology	Montreal	Quebec
Canada	Lakeridge Health Oshawa	Oshawa	Ontario
Canada	Ottawa Hospital Research Institute	Ottawa	Ontario
Canada	CHA-Hopital Du St-Sacrement	Quebec City	Quebec
Canada	CHUQ-Pavillon Hotel-Dieu de Quebec	Quebec City	Quebec
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
Canada	Atlantic Health Sciences Corporation	Saint John	New Brunswick
Canada	Saskatoon Cancer Centre	Saskatoon	Saskatchewan
Canada	Algoma District Cancer Program	Sault Ste. Marie	Ontario
Canada	Centre hospitalier universitaire de Sherbrooke	Sherbrooke	Quebec
Canada	Niagara Health System	St. Catharines	Ontario
Canada	Dr. H. Bliss Murphy Cancer Centre	St. John's	Newfoundland and Labrador
Canada	Health Sciences North	Sudbury	Ontario
Canada	BCCA - Fraser Valley Cancer Centre	Surrey	British Columbia
Canada	Thunder Bay Regional Health Science Centre	Thunder Bay	Ontario
Canada	Mount Sinai Hospital	Toronto	Ontario
Canada	Odette Cancer Centre	Toronto	Ontario
Canada	St. Michael's Hospital	Toronto	Ontario
Canada	Toronto East General Hospital	Toronto	Ontario
Canada	Univ. Health Network-Princess Margaret Hospital	Toronto	Ontario
Canada	Centre hospitalier regional de Trois-Rivieres	Trois-Rivieres	Quebec
Canada	BCCA - Vancouver Cancer Centre	Vancouver	British Columbia
Canada	BCCA - Vancouver Island Cancer Centre	Victoria	British Columbia
Canada	CancerCare Manitoba	Winnipeg	Manitoba
Japan	Chiba Cancer Center	Chiba
Japan	National Kyushu Cancer Center	Fukuoka
Japan	National Cancer Center Hospital East	Kashiwa
Japan	Kobe City Medical Center General Hospital	Kobe
Japan	National Hospital Organization Shikoku Cancer Center	Matsuyama
Japan	Kyorin University Hospital	Mitaka
Japan	Aichi Cancer Center Hospital	Nagoya
Japan	Osaka Medical Center for Cancer and Cardiovascular Diseases	Osaka
Japan	Saitama Prefectural Cancer Center	Saitama
Japan	Hokkaido University Hospital	Sapporo
Japan	Shizuoka Cancer Center	Shizuoka
Japan	Osaka Medical College Hospital	Takatsuki
Japan	Cancer Institute Hospital of JFCR	Tokyo
Japan	Keio University Hospital	Tokyo
Japan	National Cancer Center Hospital	Tokyo

Sponsors (2)

Lead Sponsor	Collaborator
NCIC Clinical Trials Group	Sumitomo Pharma Oncology, Inc.

Countries where clinical trial is conducted

Australia,  Canada,  Japan, 

References & Publications (1)

Jonker DJ, Nott L, Yoshino T, Gill S, Shapiro J, Ohtsu A, Zalcberg J, Vickers MM, Wei AC, Gao Y, Tebbutt NC, Markman B, Price T, Esaki T, Koski S, Hitron M, Li W, Li Y, Magoski NM, Li CJ, Simes J, Tu D, O'Callaghan CJ. Napabucasin versus placebo in refrac — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival	Time from the day of randomization to death. For alive patients, overall survival was censored at the last day the patient was known alive (LKA).	36 month
Secondary	Progression Free Survival	Defined as the time from randomization to the first objective documentation of disease progression or death due to any cause.	36 months
Secondary	Disease Control Rate	Proportion of all randomized patients with a documented complete response (CR) defined as disappearance of all target lesions, partial response (PR) defined as >=30% decrease in the sum of the longest diameter of target lesions, and stable disease (SD) defined as <30% decrease but also <20% increase in the sum of the longest diameter of target lesions without new lesions per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) 1.1 for target lesion.	36 months
Secondary	Number of Patients With Adverse Events	Number of patients with at least one adverse event as assessed by NCI CTCAE Version 3.0 criteria.	36 months
Secondary	Change of Global Quality of Life at 8 Weeks From Baseline	Change scores from baseline at time 2 (8 weeks) from baseline for the global health status/quality of life scale scores (between 0 and 100 with higher value indicating better quality of life) as derived from responses of patients to the EORTC (European Organisation for Research and Treatment of Cancer) quality of life questionnaire (QLQ-C30).	8 weeks