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    Summary
    EudraCT Number:2016-001627-31
    Sponsor's Protocol Code Number:CanStem303C
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2016-09-14
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedNetherlands - Competent Authority
    A.2EudraCT number2016-001627-31
    A.3Full title of the trial
    A Phase III Study of BBI-608 in combination with 5-Fluorouracil, Leucovorin, Irinotecan (FOLFIRI) in Adult Patients with Previously Treated Metastatic Colorectal Cancer (CRC)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    The aim of this study is to see how well an investigational drug (called BBI-608) works when it is given in combination with a standard anticancer treatment for people with advanced colon or rectal cancer.
    A.4.1Sponsor's protocol code numberCanStem303C
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT02753127
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorSumitomo Dainippon Pharma Oncology, Inc.
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportSumitomo Dainippon Pharma Oncology, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationSumitomo Dainippon Pharma Oncology, Inc.
    B.5.2Functional name of contact pointClinical Trial Office
    B.5.3 Address:
    B.5.3.1Street Address640 Memorial Drive
    B.5.3.2Town/ cityCambridge
    B.5.3.3Post codeMA 02139
    B.5.3.4CountryUnited States
    B.5.4Telephone number+16176746800
    B.5.5Fax number+16176748662
    B.5.6E-mailCanStem303C@bostonbiomedical.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameBBI-608 (napabucasin)
    D.3.2Product code BBI-608
    D.3.4Pharmaceutical form Capsule
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNNapabucasin
    D.3.9.1CAS number 83280-65-3
    D.3.9.3Other descriptive nameNAPABUCASIN, BBI-608, BBI608, BB608
    D.3.9.4EV Substance CodeSUB179666
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number80
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Histologically confirmed adenocarcinoma of the colon or rectum that is metastatic (Stage IV).
    E.1.1.1Medical condition in easily understood language
    Cancer of the colon or rectum.
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level LLT
    E.1.2Classification code 10052362
    E.1.2Term Metastatic colorectal cancer
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    • To compare overall survival (OS) in the General Population patients treated with BBI-608 plus biweekly FOLFIRI (Arm 1) versus biweekly FOLFIRI (Arm 2)
    • To compare OS in the pSTAT3-positive (pSTAT3(+)) Subpopulation patients treated with BBI-608 plus biweekly FOLFIRI (Arm 1) versus biweekly FOLFIRI (Arm 2)
    E.2.2Secondary objectives of the trial
    Key Secondary Objectives:
    • To compare progression free survival (PFS) in the General Population patients treated with BBI-608 plus biweekly FOLFIRI versus biweekly FOLFIRI
    • To compare PFS in the pSTAT3(+) Subpopulation patients treated with BBI 608 plus biweekly FOLFIRI versus biweekly FOLFIRI
    • To compare disease control rate (DCR) in the General Population patients treated with BBI-608 plus biweekly FOLFIRI versus biweekly FOLFIRI
    • To compare DCR in the pSTAT3(+) Subpopulation patients treated with BBI-608 plus biweekly FOLFIRI versus biweekly FOLFIRI
    • To compare overall response rate (ORR) in the General Population patients treated with BBI-608 plus biweekly FOLFIRI versus biweekly FOLFIRI
    • To compare ORR in the pSTAT3(+) Subpopulation patients treated with BBI-608 plus biweekly FOLFIRI versus biweekly FOLFIRI

    Please refer to the protocol for other Secondary Objectives.

    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1.1 Written, signed consent for trial participation must be obtained from the patient appropriately in accordance with applicable ICH guidelines and local and regulatory requirements prior to the performance of any study specific procedure.
    1.2 Must have histologically confirmed advanced CRC that is metastatic.
    1.3 Must have failed treatment with one regimen containing only a fluoropyrimidine and oxaliplatin with or without bevacizumab for metastatic disease. All patients must have received a minimum of 6 weeks of the first-line regimen that included oxaliplatin and a fluoropyrimidine with or without bevacizumab in the same cycle. Treatment failure is defined as radiologic progression during or < 6 months after the last dose of first-line therapy.
    1.4 FOLFIRI therapy is appropriate for the patient and is recommended by the Investigator.
    1.5 Imaging investigations including CT/MRI of chest/abdomen/pelvis or other scans as necessary to document all sites of disease performed within 21 days prior to randomization. Patients with either measurable disease or non-measurable evaluable disease are eligible.
    1.6 Must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
    1.7 Must be ≥ 18 years of age.
    1.8 For male or female patient of child bearing potential: Must agree to use contraception or take measures to avoid pregnancy during the study and for 180 days for female and for male patients, of the final FOLFIRI dose. Patients who receive single agent BBI-608 without FOLFIRI must agree to use contraception or take measures to avoid pregnancy during the study and for 30 days for female patients and 90 days for male patients, of the final BBI-608 dose.
    Female patients of child bearing potential treated with bevacizumab, per investigator choice, must agree to use contraception or take measures to avoid pregnancy during the study and for 6 months, of the final bevacizumab dose.
    1.9 Women of child bearing potential (WOCBP) must have a negative serum or urine pregnancy test within 5 days prior to randomization. The minimum sensitivity of the pregnancy test must be 25 IU/L or equivalent units of HCG.
    1.10 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.
    1.11 Must have hemoglobin (Hgb) ≥ 9.0 g/dL within 14 days prior to randomization. Must not have required transfusion of red blood cells within 1 week of baseline Hgb assessment.
    1.12 Must have total bilirubin ≤ 1.5 × institutional ULN [≤ 2.0 x ULN in presence of liver metastases] within 14 days prior to randomization.
    1.13 Must have creatinine ≤ 1.5 × institutional ULN or Creatinine Clearance > 50 ml/min as calculated by the Cockcroft-Gault equation (CKD-EPI equation may also be used) within 14 days prior to randomization.
    1.14 Must have absolute neutrophil count ≥ 1.5 x 109/L within 14 days prior to randomization.
    1.15 Must have platelet count ≥ 100 x 109/L within 14 days prior to randomization. Must not have required transfusion of platelets within 1 week of baseline platelet assessment.
    1.16 Patient must have adequate nutritional status with Body Mass Index (BMI) > 18 kg/m2 and body weight of > 40 kg with serum albumin > 3 g/dL.
    1.17 Other baseline laboratory evaluations must be done within 14 days prior to randomization.
    1.18 Patient must consent to provision of, and Investigator(s) must confirm access to and agree to submit a representative formalin fixed paraffin block of tumor tissue in order that the specific biomarker assays may be conducted (section 12.2.1 and Section 13.2).
    1.19 Patient must consent to provision of a sample of blood in order that the specific correlative marker assays may be conducted (section 12.2.1).
    1.20 Patients must be accessible for treatment and follow-up.
    1.21 Protocol treatment is to begin within 2 calendar days of patient randomization for patients randomized to Arm 1. Patients randomized to Arm 2 must begin protocol treatment within 7 calendar days of randomization.

    (Please refer to protocol for further information)
    E.4Principal exclusion criteria
    2.1 Anti-cancer chemotherapy or biologic therapy if administered prior to the first planned dose of study medication (BBI-608 or FOLFIRI) within period of time equivalent to the usual cycle length of the regimen. An exception is made for oral fluoropyrimidines (e.g. capecitabine, S-1), where a minimum of 10 days since last dose must be observed prior to the first planned dose of study medication.
    2.2 More than one prior chemotherapy regimen administered in the metastatic setting.
    2.3 Major surgery within 4 weeks prior to randomization.
    2.4 Patients with any known brain or leptomeningeal metastases are excluded, even if treated.
    2.5 Women who are pregnant or breastfeeding. Women should not breastfeed while taking study treatment and for 4 weeks after the last dose of BBI-608 or while undergoing treatment with FOLFIRI and for 180 days after the last dose of FOLFIRI.
    2.6 Gastrointestinal disorder(s) which, in the opinion of the Qualified/Principal Investigator, would significantly impede the absorption of an oral agent (e.g. intestinal occlusion, active Crohn’s disease, ulcerative colitis, extensive gastric and small intestine resection).
    2.7 Unable or unwilling to swallow BBI-608 capsules daily.
    2.8 Prior treatment with BBI-608 or possible hypersensitivity to BBI-608 or one of the excipients which include azo dyes sunset yellow and allura red.
    2.9 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.
    a. Known infection with Human Immunodeficiency Virus (HIV), and/or active infection with hepatitis B (patients who have had an HBV immunization are eligible), or hepatitis C.
    b. Patients with clinically significant ascites or pleural effusions.
    2.10 Known hypersensitivity to 5-fluorouracil/leucovorin
    2.11 Known dihydropyrimidine dehydrogenase (DPD) deficiency
    2.12 Known hypersensitivity to irinotecan
    2.13 Chronic inflammatory bowel disease (Crohn’s disease or ulcerative colitis)
    2.14 Patients receiving treatment with St. John’s wort or Phenytoin.
    2.15 Patients who plan to receive yellow fever vaccine during the course of the study treatment.
    2.16 Abnormal glucuronidation of bilirubin, known Gilbert’s syndrome
    2.17 Patients with QTc interval > 470 milliseconds
    2.18 For patients to be treated with a regimen containing bevacizumab: please refer to protocol
    2.19 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 tumors curatively treated with no evidence of disease for > 3 years.
    2.20 Any active disease condition which would render the protocol treatment dangerous or impair the ability of the patient to receive protocol therapy.
    2.21 Any condition (e.g. psychological, geographical, etc.) that does not permit compliance with the protocol.

    Please refer to protocol for further information.
    E.5 End points
    E.5.1Primary end point(s)
    The primary study endpoints are Overall Survival for the General Population and the pSTAT3(+) Subpopulation.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Without adjusting for multiplicity, it is estimated that 850 events in the General Population and 310 (approximately 36% of 850) events in the pSTAT3(+) Subpopulation will be required to detect the reduction in the risk of death, which would be observed by randomizing 1250 patients (General Population) over 26 months with patient follow up for an additional 14 months, for a total study duration of 40 months. It is anticipated that up to 5% dropout rate will occur over the entire study.

    Please refer to the protocol for further information
    E.5.2Secondary end point(s)
    • Progression Free Survival in the general study population and the pSTAT3(+) Subpopulation
    • Objective Response Rate (ORR) in the general study population
    and the pSTAT3(+) Subpopulation
    • Disease Control Rate (DCR) in the general study population and the pSTAT3(+) Subpopulation
    • Safety Profile in the general study population and the pSTAT3(+) Subpopulation
    • Quality of Life (QoL) in the general study population and the pSTAT3(+) Subpopulation
    E.5.2.1Timepoint(s) of evaluation of this end point
    Please refer to protocol for further information.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis Yes
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Efficacy Quality of Life
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    Standard background therapy per protocol without addition of IMP
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned5
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA71
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Australia
    Canada
    China
    Hong Kong
    Israel
    Japan
    Korea, Republic of
    Singapore
    United States
    Belgium
    Czechia
    France
    Germany
    Italy
    Netherlands
    Spain
    Sweden
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The primary endpoint is Overall Survival (OS) in the General Population and the pSTAT3(+) Subpopulation. Patients who are alive at the time of the interim or the final analysis or who have become lost to follow-up will become censored on the date the patient was last known to be alive.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    E.8.9.1In the Member State concerned months7
    E.8.9.1In the Member State concerned days17
    E.8.9.2In all countries concerned by the trial years5
    E.8.9.2In all countries concerned by the trial months3
    E.8.9.2In all countries concerned by the trial days14
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 750
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 500
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state66
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 373
    F.4.2.2In the whole clinical trial 1250
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    None - After permanent discontinuation of protocol therapy, patients will receive subsequent anti-cancer treatment and care at the Investigator's discretion. Patients in this trial will be followed until death, the primary endpoint of this study.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2016-09-14
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-11-10
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2021-05-06
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