The purpose of this study is to find out whether it is better to receive treatment with paclitaxel, a standard chemotherapy, given in combination with a new drug, BBI608, or better to receive treatment with paclitaxel alone for stomach and gastroesophageal junction cancer. To do this, half of the patients in this study will receive paclitaxel and BBI608 and the other half will receive paclitaxel and a placebo (a substance that is designed not to do anything).

• Register: EUCTR
• Last refreshed on: 5 April 2021
• Main ID: EUCTR2014-000774-18-DE
• Date of registration: 09/09/2014
• Prospective Registration: Yes
• Primary sponsor: Boston Biomedical, Inc.
• Public title: The purpose of this study is to find out whether it is better to receive treatment with paclitaxel, a standard chemotherapy, given in combination with a new drug, BBI608, or better to receive treatment with paclitaxel alone for stomach and gastroesophageal junction cancer. To do this, half of the patients in this study will receive paclitaxel and BBI608 and the other half will receive paclitaxel and a placebo (a substance that is designed not to do anything).
• Scientific title: A Phase III Randomized, Double-Blind, Placebo-Controlled Clinical Trial of BBI608 plus Weekly Paclitaxel vs. Placebo plus Weekly Paclitaxel in Adult Patients with Advanced, Previously Treated Gastric and Gastro-Esophageal Junction Adenocarcinoma - BRIGHTER
• Date of first enrolment: 25/11/2014
• Target sample size: 700
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-000774-18
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Belgium, Brazil, Bulgaria, Canada, China, Czech Republic, Estonia, France, Germany, Hungary, Iceland, Israel, Italy, Japan, Korea, Republic of, Lithuania, Poland, Romania, Russian Federation, Spain, Taiwan, United Kingdom, United States

Contacts

• Name: Clinical Trials Office
• Affiliation: Boston Biomedical, Inc.

• Name: Clinical Trials Office
• Affiliation: Boston Biomedical, Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Written, signed consent for trial participation must be obtained
2. Must have cytologically or histologically confirmed advanced gastric or GEJ adenocarcinoma that is metastatic or locally advanced and unresectable (with unresectability as defined by National Comprehensive
Cancer Network Guidelines for Gastric Cancer [Version 2.2013] and Esophageal and Esophagogastric Junction Cancer [Version 2.2013]).GEJ cancers may include Siewert Class I, II or III types [Siewert 1996].
3. Must have failed treatment with one regimen containing at least a platinum/fluoropyrimidine doublet for unresectable or metastatic disease. While not mandated, concomitant treatment with an anthracycline (epirubicin or doxorubicin), or anti-HER2 therapy (trastuzumab) in this setting is allowed. Patients who have progression of disease at any point during neoadjuvant or adjuvant treatment with aplatinum/fluoropyrimidine doublet or < 6 months after the last dose of neoadjuvant or adjuvant treatment may be enrolled.Treatment failure is defined as progression of disease (clinical or radiologic) during first line treatment for unresectable or metastatic disease or = 6 months after last dose of first line treatment. No additional prior lines of therapy in
the metastatic setting will be allowed. A patient who has received neoadjuvant or adjuvant treatment, relapsed, and then received a platinum/fluoropyrimidine doublet as first-line treatment in the unresectable/metastatic setting would be allowed, however. Patients who have received prior taxane therapy may be enrolled, so long as the taxane was administered in the adjuvant or neoadjuvant setting and progression occurred more than 6 months following completion of therapy. Patients who were intolerant to paclitaxel are not allowed, however.
4. Paclitaxel therapy is appropriate for the patient and is recommended by the Investigator.
5. Imaging investigations including CT/MRI of chest/abdomen/pelvis or other scans as necessary to document all sites of disease done within 21 days prior to randomization. Patients with either measurable disease OR
non-measurable evaluable disease will be eligible.
6. Must have an Eastern Cooperative Oncology Group (ECOG)
Performance Status of 0 or 1.
7. Must be = 18 years of age.
8. 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 6 months after the final dose of Paclitaxel or for 30 days for
female patients and for 90 days for male patients, of the final BBI608/Placebo dose if Paclitaxel was not administered.
9. 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.
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.
11. Must have hemoglobin (Hgb) = 9.0 g/dL within 14 days prior to randomization. Must not have required transfusion within 1 week of baseline Hgb assessment.
12. Must have total bilirubin = 1.5 × institutional ULN [= 2.0 x ULN in presence of liver metastases] within 14 days prior to randomization.
13. Must have creatinine = 1.5 × institutional ULN or Creatinine Clearance > 50 ml/min (as calculated by the Cockroft-Gault equation) within 14 days prior to randomization.
14. Must have absolute neutrophil count = 1.5 x
Exclusion criteria:
1. Anti-cancer chemotherapy or biologic therapy if administered prior to the first planned dose of BBI608/placebo 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 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.
2. Prior taxane therapy in the neoadjuvant or adjuvant setting with progression occurring within 6 months of completion of taxane therapy; or any taxane therapy in the metastatic setting.
3. More than one prior chemotherapy regimen administered in the metastatic setting.
4. Major surgery within 4 weeks prior to randomization.
5. Any known symptomatic brain metastases requiring steroids. Patients with treated brain metastases must be stable for 4 weeks after completion of that treatment, with image documentation required. Patients must have no clinical symptoms from brain metastases and must be either off steroids, or on a stable dose of steroids for at least 2 weeks prior to randomization. Patients with known leptomeningeal metastases are excluded, even if treated.
6. Women who are pregnant or breastfeeding.
7. 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).
8. Severe hepatic impairment as per the Paclitaxel Summary of Product Characteristics.
9. History of severe hypersensitivity to paclitaxel or to any of the excipients, including macrogolglycerol ricinoleate.
10. Unable or unwilling to swallow BBI608/placebo capsules daily.
11. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, clinically significant non-healing or healing wounds, symptomatic congestive heart failure (> class II New York Heart Association (NYHA), unstable angina pectoris (including angina symptoms at rest, new onset angina begun < 3 months prior, or myocardial infarction < 6 months prior), clinically significant cardiac arrhythmia requiring anti-arrhythmic therapy, clinically significant valvular or pericardial disease, severe uncontrolled arterial
hypertension, 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.
12. Peripheral neuropathy = CTCAE Grade 2 at baseline
13. Patients with a history of other malignancies except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, and in-situ cancer of the urinary bladder, or other solid tumors curatively treated with no evidence of disease for > 3 years.
14. Prior treatment with BBI608
15. Any active disease condition which would render the protocol treatment dangerous or impair the ability of the patient to receive protocol therapy.
16. Any condition (e.g. psychological, geographical, etc.) that does not permit compliance with the protocol.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Advanced (metastatic or locally advanced and unresectable), gastric or gastroesophageal junction (GEJ) adenocarcinoma
MedDRA version: 18.1 Level: PT Classification code 10063916 Term: Metastatic gastric cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Product Name: BBI608
Product Code: BBI608
Pharmaceutical Form: Capsule
INN or Proposed INN: Napabucasin
CAS Number: 83280-65-3
Current Sponsor code: BBI608
Other descriptive name: BBI608
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 80-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Trade Name: Paclitaxel 6mg /ml concentrate for solution for infusion
Product Name: Paclitaxel 6 mg/ml concentrate for solution for infusion
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: PACLITAXEL
CAS Number: 33069-62-4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 6-

Trade Name: Paclitaxel 6mg /ml concentrate for solution for infusion
Product Name: Paclitaxel 6 mg/ml concentrate for solution for infusion
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: PACLITAXEL
CAS Number: 33069-62-4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 6-

Trade Name: Paclitaxel 6mg /ml concentrate for solution for infusion
Product Name: Paclitaxel 6 mg/ml concentrate for solution for infusion
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: PACLITAXEL
CAS Number: 33069-62-4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 6-

Trade Name: Paclitaxel 6mg /ml concentrate for solution for infusion
Product Name: Paclitaxel 6 mg/ml concentrate for solution for infusion
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: PACLITAXEL
CAS Number: 33069-62-4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 6-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Overall survival is defined as the time from randomization to death from any cause.
Evaluation occurs at the first regularly scheduled 4 week assessment at which the patient has been off study therapy for a minimum of 28 days, and every 8 weeks (56 days) thereafter. (+/- 3 days)

Primary end point(s): Overall survival (OS)

Main Objective: To compare overall survival (OS) of patients with pre-treated, advanced gastric and gastro-esophageal junction (GEJ) adenocarcinoma treated with BBI608 plus weekly paclitaxel versus placebo plus weekly paclitaxel. OS is defined as the time from randomization until death from any cause.

Secondary Objective: To evaluate the safety profile of BBI608 administered daily plus weekly
paclitaxel in patients with pre-treated advanced gastric/GEJ
adenocarcinoma, with safety assessed according to the National Cancer
Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE)
version 4.0.

Secondary Outcome(s)

Secondary end point(s): Overall Survival (OS) in the biomarker-positive population [those patients with nuclear ß-catenin
positivity on immunohistochemical (IHC) staining of Formalin Fixed Paraffin Embedded (FFPE)
archival tissue].

Progression-Free Survival (PFS) in the General Study Population

Progression-Free Survival in the Predefined Biomarker-positive Population [those patients with nuclear ß-catenin positivity on immunohistochemical (IHC) staining of Formalin Fixed Paraffin Embedded (FFPE)
archival tissue]

Objective Response Rate (ORR) in the General Study Population

Disease Control Rate (DCR) in the General Study Population

Safety Profile

Timepoint(s) of evaluation of this end point: Evaluations will be performed at different intervals throughout the study:
If dose delays occur for any reason on the study, other study assessments, including assessment by physician and Quality of Life questionnaires, will not be delayed, but should continue at the time indicated in the protocol from randomization.

Secondary ID(s)

NCT02178956

2014-000774-18-ES

BBI608-336

Source(s) of Monetary Support

Boston Biomedical, Inc.

Ethics review

Status: Approved
Approval date: 09/09/2014
Contact:

Results

• Results available: Yes
• Date Posted: 12/10/2019
• Date Completed: 20/09/2017
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-000774-18/results