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

NCT ID: NCT01830621

Last Updated: 2023-08-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 282 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-05-10
• Study Completion Date: 2016-05-16

Brief 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).

Detailed 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.

Conditions

Colorectal Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

BBI608

BBI608 480 mg two times daily (960 mg total daily dose)+ Best Supportive Care

Group Type: ACTIVE_COMPARATOR

BBI608

Intervention Type: DRUG

Best Supportive Care

Intervention Type: OTHER

Placebo

Placebo two times daily + Best Supportive Care

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Best Supportive Care

Intervention Type: OTHER

Interventions

BBI608

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Best Supportive Care

Intervention Type: OTHER

Eligibility Criteria

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.

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

Sponsors

Sumitomo Pharma America, Inc.

INDUSTRY

Sponsor Role: collaborator

NCIC Clinical Trials Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Derek Jonker

Role: STUDY_CHAIR

Ottawa Health Research Institute - General Division

Locations

Bankstown/ Lidcombe

Bankstown, New South Wales, Australia

Townsville Hospital

Douglas, Queensland, Australia

Flinders Medical Centre

Bedford Park, South Australia, Australia

Lyell McEwin Hospital

Elizabeth Vale, South Australia, Australia

The Queen Elizabeth Hospital

Woodville South, South Australia, Australia

Royal Hobart Hospital

Hobart, Tasmania, Australia

Peter MacCallum Cancer Institute

East Melbourne, Victoria, Australia

St John of God - Subiaco

Subiaco, Western Australia, Australia

St John of God Bunbury Hospital

Bunbury, , Australia

Tom Baker Cancer Centre

Calgary, Alberta, Canada

Cross Cancer Institute

Edmonton, Alberta, Canada

BCCA - Abbotsford Centre

Abbotsford, British Columbia, Canada

BCCA - Cancer Centre for the Southern Interior

Kelowna, British Columbia, Canada

BCCA - Fraser Valley Cancer Centre

Surrey, British Columbia, Canada

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, Canada

BCCA - Vancouver Island Cancer Centre

Victoria, British Columbia, Canada

CancerCare Manitoba

Winnipeg, Manitoba, Canada

Horizon Health Network,

Fredericton, New Brunswick, Canada

The Moncton Hospital

Moncton, New Brunswick, Canada

The Vitalite Health Network - Dr. Leon Richard

Moncton, New Brunswick, Canada

Atlantic Health Sciences Corporation

Saint John, New Brunswick, Canada

Dr. H. Bliss Murphy Cancer Centre

St. John's, Newfoundland and Labrador, Canada

QEII Health Sciences Centre

Halifax, Nova Scotia, Canada

The Royal Victoria Hospital

Barrie, Ontario, Canada

Health Sciences North

Greater Sudbury, Ontario, Canada

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, Canada

London Regional Cancer Program

London, Ontario, Canada

Credit Valley Hospital

Mississauga, Ontario, Canada

Lakeridge Health Oshawa

Oshawa, Ontario, Canada

Ottawa Hospital Research Institute

Ottawa, Ontario, Canada

Algoma District Cancer Program

Sault Ste. Marie, Ontario, Canada

Niagara Health System

St. Catharines, Ontario, Canada

Thunder Bay Regional Health Science Centre

Thunder Bay, Ontario, Canada

Toronto East General Hospital

Toronto, Ontario, Canada

Odette Cancer Centre

Toronto, Ontario, Canada

St. Michael's Hospital

Toronto, Ontario, Canada

Mount Sinai Hospital

Toronto, Ontario, Canada

Univ. Health Network-Princess Margaret Hospital

Toronto, Ontario, 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

McGill University - Dept. Oncology

Montreal, Quebec, Canada

CHUQ-Pavillon Hotel-Dieu de Quebec

Québec, Quebec, Canada

CHA-Hopital Du St-Sacrement

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

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, , Japan

Countries

Australia; Canada; Japan

References

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 refractory advanced colorectal cancer: a randomised phase 3 trial. Lancet Gastroenterol Hepatol. 2018 Apr;3(4):263-270. doi: 10.1016/S2468-1253(18)30009-8. Epub 2018 Feb 1.

Reference Type: RESULT

PMID: 29397354 (View on PubMed)

Other Identifiers

CO23

Identifier Type: -

Identifier Source: org_study_id