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

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ClinicalTrials.gov Identifier: NCT01830621
Recruitment Status : Completed
First Posted : April 12, 2013
Last Update Posted : February 8, 2018
Sponsor:
Collaborator:
Boston Biomedical, Inc
Information provided by (Responsible Party):
Canadian Cancer Trials Group ( NCIC Clinical Trials Group )

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).

Condition or disease Intervention/treatment Phase
Colorectal Carcinoma Drug: BBI608 Drug: Placebo Other: Best Supportive Care Phase 3

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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 282 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
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
Study Start Date : April 2013
Actual Primary Completion Date : August 2015
Actual Study Completion Date : May 2016

Arm Intervention/treatment
Active Comparator: BBI608
BBI608 480 mg two times daily (960 mg total daily dose)+ Best Supportive Care
Drug: BBI608
Other: Best Supportive Care
Placebo Comparator: Placebo
Placebo two times daily + Best Supportive Care
Drug: Placebo
Other: Best Supportive Care



Primary Outcome Measures :
  1. Overall Survival [ Time Frame: 38 month ]
    The primary objective of this study is to assess the effect of orally administered BBI608 plus best supportive care (BSC), in comparison to placebo plus best supportive care on the Overall Survival of patients with advanced histopathologically confirmed colorectal carcinoma who have exhausted all standard treatment options


Secondary Outcome Measures :
  1. Progression Free Survival [ Time Frame: 38 months ]
    Defined as the time from randomization to the first objective documentation of disease progression or death due to any cause.

  2. Disease Control Rate [ Time Frame: 38 months ]
    Defined as the proportion of patients with a documented complete response, partial response, and stable disease (CR + PR + SD) based on RECIST 1.1.

  3. Number of Patients with Adverse Events [ Time Frame: 38 months ]
    All patients who have received at least one dose of BBI608/Placebo will be included in the safety analysis. The incidence of adverse events will be summarized by type of adverse event and severity.

  4. Quality of Life [ Time Frame: 38 months ]
    The primary endpoints in QoL analysis are the mean EORTC QLQ-C30 QoL change scores from baseline at time 2 (8 weeks) and time 4 (16 weeks) for the physical function and global health status/quality of life subscale scores.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01830621


  Show 63 Study Locations
Sponsors and Collaborators
NCIC Clinical Trials Group
Boston Biomedical, Inc
Investigators
Study Chair: Derek Jonker Ottawa Health Research Institute - General Division

Publications of Results:
Responsible Party: NCIC Clinical Trials Group
ClinicalTrials.gov Identifier: NCT01830621     History of Changes
Other Study ID Numbers: CO23
First Posted: April 12, 2013    Key Record Dates
Last Update Posted: February 8, 2018
Last Verified: May 2016

Additional relevant MeSH terms:
Carcinoma
Colorectal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases