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

NCT01830621 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: CO23
• Study Type: interventional
• Target: 282
• Locations: 3 countries
• Sites: 63

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).

Conditions

Colorectal Carcinoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Progression Free Survival

  36 months

• Disease Control Rate

  36 months

• Number of Patients With Adverse Events

  36 months

• Change of Global Quality of Life at 8 Weeks From Baseline

  8 weeks

Study Arms (2)

BBI608

ACTIVE COMPARATOR

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

Drug: BBI608; Other: Best Supportive Care

Placebo

PLACEBO COMPARATOR

Placebo two times daily + Best Supportive Care

Drug: Placebo; Other: Best Supportive Care

Interventions

BBI608 DRUG

BBI608

Placebo DRUG

Placebo

Best Supportive Care OTHER

BBI608; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• NCIC Clinical Trials Group: lead
• Sumitomo Pharma America, Inc.: collaborator

Study Sites (63)

Bankstown/ Lidcombe

Bankstown, New South Wales, 2200, Australia

Location

Townsville Hospital

Douglas, Queensland, 4814, Australia

Location

Flinders Medical Centre

Bedford Park, South Australia, 5042, Australia

Location

Lyell McEwin Hospital

Elizabeth Vale, South Australia, 5112, Australia

Location

The Queen Elizabeth Hospital

Woodville South, South Australia, 5011, Australia

Location

Royal Hobart Hospital

Hobart, Tasmania, 7000, Australia

Location

Peter MacCallum Cancer Institute

East Melbourne, Victoria, 3002, Australia

Location

St John of God - Subiaco

Subiaco, Western Australia, 6008, Australia

Location

St John of God Bunbury Hospital

Bunbury, 6230, Australia

Location

Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

BCCA - Abbotsford Centre

Abbotsford, British Columbia, V2S 0C2, Canada

Location

BCCA - Cancer Centre for the Southern Interior

Kelowna, British Columbia, V1Y 5L3, Canada

Location

BCCA - Fraser Valley Cancer Centre

Surrey, British Columbia, V3V 1Z2, Canada

Location

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

BCCA - Vancouver Island Cancer Centre

Victoria, British Columbia, V8R 6V5, Canada

Location

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

Horizon Health Network,

Fredericton, New Brunswick, E3B 5N5, Canada

Location

The Moncton Hospital

Moncton, New Brunswick, E1C 6Z8, Canada

Location

The Vitalite Health Network - Dr. Leon Richard

Moncton, New Brunswick, E1C 8X3, Canada

Location

Atlantic Health Sciences Corporation

Saint John, New Brunswick, E2L 4L2, Canada

Location

Dr. H. Bliss Murphy Cancer Centre

St. John's, Newfoundland and Labrador, A1B 3V6, Canada

Location

QEII Health Sciences Centre

Halifax, Nova Scotia, B3H 1V7, Canada

Location

The Royal Victoria Hospital

Barrie, Ontario, L4M 6M2, Canada

Location

Health Sciences North

Greater Sudbury, Ontario, P3E 5J1, Canada

Location

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

London Regional Cancer Program

London, Ontario, N6A 4L6, Canada

Location

Credit Valley Hospital

Mississauga, Ontario, L5M 2N1, Canada

Location

Lakeridge Health Oshawa

Oshawa, Ontario, L1G 2B9, Canada

Location

Ottawa Hospital Research Institute

Ottawa, Ontario, K1H 8L6, Canada

Location

Algoma District Cancer Program

Sault Ste. Marie, Ontario, P6B 0A8, Canada

Location

Niagara Health System

St. Catharines, Ontario, L2S 0A9, Canada

Location

Thunder Bay Regional Health Science Centre

Thunder Bay, Ontario, P7B 6V4, Canada

Location

Toronto East General Hospital

Toronto, Ontario, M4C 3E7, Canada

Location

Odette Cancer Centre

Toronto, Ontario, M4N 3M5, Canada

Location

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

Mount Sinai Hospital

Toronto, Ontario, M5G 1X5, Canada

Location

Univ. Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Hopital de la Cite-de-la-Sante

Laval, Quebec, H7M 3L9, Canada

Location

L'Hotel-Dieu de Levis

Lévis, Quebec, G6V 3Z1, Canada

Location

CHUM - Hopital Notre-Dame

Montreal, Quebec, H2L 4M1, Canada

Location

McGill University - Dept. Oncology

Montreal, Quebec, H2W 1S6, Canada

Location

CHUQ-Pavillon Hotel-Dieu de Quebec

Québec, Quebec, G1R 2J6, Canada

Location

CHA-Hopital Du St-Sacrement

Québec, Quebec, G1S 4L8, Canada

Location

Centre hospitalier universitaire de Sherbrooke

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Centre hospitalier regional de Trois-Rivieres

Trois-Rivières, Quebec, G8Z 3R9, Canada

Location

Allan Blair Cancer Centre

Regina, Saskatchewan, S4T 7T1, Canada

Location

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, S7N 4H4, Canada

Location

Chiba Cancer Center

Chiba, Japan

Location

National Kyushu Cancer Center

Fukuoka, Japan

Location

National Cancer Center Hospital East

Kashiwa, Japan

Location

Kobe City Medical Center General Hospital

Kobe, Japan

Location

National Hospital Organization Shikoku Cancer Center

Matsuyama, Japan

Location

Kyorin University Hospital

Mitaka, Japan

Location

Aichi Cancer Center Hospital

Nagoya, Japan

Location

Osaka Medical Center for Cancer and Cardiovascular Diseases

Osaka, Japan

Location

Saitama Prefectural Cancer Center

Saitama, Japan

Location

Hokkaido University Hospital

Sapporo, Japan

Location

Shizuoka Cancer Center

Shizuoka, Japan

Location

Osaka Medical College Hospital

Takatsuki, Japan

Location

Cancer Institute Hospital of JFCR

Tokyo, Japan

Location

Keio University Hospital

Tokyo, Japan

Location

National Cancer Center Hospital

Tokyo, Japan

Location

Related 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 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.

  PMID: 29397354 RESULT

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

napabucasin

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Results Point of Contact

• Title: Dr. Derek Jonker
• Organization: The Ottawa Hospital Regional Cancer Centre

djonker@ottawahospital.on.ca

613-737-7700

Study Officials

• Derek Jonker

  Ottawa Health Research Institute - General Division

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2013
• First Posted: April 12, 2013
• Study Start: May 10, 2013
• Primary Completion: May 7, 2016
• Study Completion: May 16, 2016
• Last Updated: August 28, 2023
• Results First Posted: March 11, 2019

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

JP (15); AU (9); CA (39)