Trial Outcomes & Findings for A Study of BBI608 Plus Weekly Paclitaxel to Treat Gastric and Gastro-Esophageal Junction Cancer (NCT NCT02178956)

Last Updated: 2023-11-15

Results Overview

The primary objective of this study is to assess the effect of orally administered BBI608 plus weekly paclitaxel, in comparison to placebo plus weekly paclitaxel on the Overall Survival of patients with advanced histopathologically confirmed gastric or gastroesophageal junction adenocarcinoma who failed treatment with one platinum/fluoropyrimidine containing regimen for unresectable or metastatic disease.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

714 participants

Primary outcome timeframe

36 months

Results posted on

2023-11-15

Participant Flow

714 patients were enrolled to this study from 02OCT2014 to 20SEP2017 across 204 sites in 22 countries.

Study arm was determined at patient randomization to the study, no pre-assignment activities occurred.

Participant milestones

Participant milestones
Measure	Napabucasin + Paclitaxel Napabucasin was administered orally, twice daily, with doses separated by 12 hours. Paclitaxel 80 mg/m2 (intravenous \[IV\]) was administered weekly, on Days 1, 8, and 15 of each 28 day study cycle. Napabucasin administration began 2 days prior to the first paclitaxel infusion in the initial run in period.	Placebo + Paclitaxel Placebo was administered orally, twice daily, with doses separated by 12 hours. Paclitaxel 80 mg/m2 (intravenous \[IV\]) was administered weekly, on Days 1, 8, and 15 of each 28 day study cycle. Placebo administration began 2 days prior to the first paclitaxel infusion in the initial run in period.
Overall Study STARTED	357	357
Overall Study COMPLETED	286	279
Overall Study NOT COMPLETED	71	78

Reasons for withdrawal

Reasons for withdrawal
Measure	Napabucasin + Paclitaxel Napabucasin was administered orally, twice daily, with doses separated by 12 hours. Paclitaxel 80 mg/m2 (intravenous \[IV\]) was administered weekly, on Days 1, 8, and 15 of each 28 day study cycle. Napabucasin administration began 2 days prior to the first paclitaxel infusion in the initial run in period.	Placebo + Paclitaxel Placebo was administered orally, twice daily, with doses separated by 12 hours. Paclitaxel 80 mg/m2 (intravenous \[IV\]) was administered weekly, on Days 1, 8, and 15 of each 28 day study cycle. Placebo administration began 2 days prior to the first paclitaxel infusion in the initial run in period.
Overall Study Lost to Follow-up	4	4
Overall Study Sponsor terminated study	49	58
Overall Study Withdrawal by Subject	15	11
Overall Study Various Reasons	3	5

Baseline Characteristics

A Study of BBI608 Plus Weekly Paclitaxel to Treat Gastric and Gastro-Esophageal Junction Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Napabucasin + Paclitaxel n=357 Participants Napabucasin was administered orally, twice daily, with doses separated by 12 hours. Paclitaxel 80 mg/m2 (intravenous \[IV\]) was administered weekly, on Days 1, 8, and 15 of each 28 day study cycle. Napabucasin administration began 2 days prior to the first paclitaxel infusion in the initial run in period.	Placebo + Paclitaxel n=357 Participants Placebo was administered orally, twice daily, with doses separated by 12 hours. Paclitaxel 80 mg/m2 (intravenous \[IV\]) was administered weekly, on Days 1, 8, and 15 of each 28 day study cycle. Placebo administration began 2 days prior to the first paclitaxel infusion in the initial run in period.	Total n=714 Participants Total of all reporting groups
Age, Continuous	60.787 years STANDARD_DEVIATION 11.5130 • n=5 Participants	59.887 years STANDARD_DEVIATION 11.1231 • n=7 Participants	60.337 years STANDARD_DEVIATION 11.3207 • n=5 Participants
Sex: Female, Male Female	96 Participants n=5 Participants	103 Participants n=7 Participants	199 Participants n=5 Participants
Sex: Female, Male Male	261 Participants n=5 Participants	254 Participants n=7 Participants	515 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	107 Participants n=5 Participants	102 Participants n=7 Participants	209 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) White	237 Participants n=5 Participants	240 Participants n=7 Participants	477 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	11 Participants n=5 Participants	11 Participants n=7 Participants	22 Participants n=5 Participants
ECOG 0: Fully active, able to carry on all pre-disease performance without restriction	128 Participants n=5 Participants	134 Participants n=7 Participants	262 Participants n=5 Participants
ECOG 1: Restricted in physically strenuous activity but ambulatory, can carry out light/sedentary work	229 Participants n=5 Participants	223 Participants n=7 Participants	452 Participants n=5 Participants
BMI	23.24 kg/m^2 STANDARD_DEVIATION 4.481 • n=5 Participants	23.56 kg/m^2 STANDARD_DEVIATION 4.709 • n=7 Participants	23.40 kg/m^2 STANDARD_DEVIATION 4.596 • n=5 Participants

PRIMARY outcome

Timeframe: 36 months

Outcome measures

Outcome measures
Measure	Napabucasin + Paclitaxel n=357 Participants Napabucasin was administered orally, twice daily, with doses separated by 12 hours. Paclitaxel 80 mg/m2 (intravenous \[IV\]) was administered weekly, on Days 1, 8, and 15 of each 28 day study cycle. Napabucasin administration began 2 days prior to the first paclitaxel infusion in the initial run in period.	Placebo + Paclitaxel n=357 Participants Placebo was administered orally, twice daily, with doses separated by 12 hours. Paclitaxel 80 mg/m2 (intravenous \[IV\]) was administered weekly, on Days 1, 8, and 15 of each 28 day study cycle. Placebo administration began 2 days prior to the first paclitaxel infusion in the initial run in period.
Overall Survival	6.93 Months Interval 6.28 to 7.69	7.36 Months Interval 6.64 to 8.15

SECONDARY outcome

Timeframe: 36 months

Defined as the time from randomization to the first objective documentation of disease progression or death due to any cause which comes first. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria(RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in anon-target lesion, or the appearance of new lesions.

Outcome measures

Outcome measures
Measure	Napabucasin + Paclitaxel n=357 Participants Napabucasin was administered orally, twice daily, with doses separated by 12 hours. Paclitaxel 80 mg/m2 (intravenous \[IV\]) was administered weekly, on Days 1, 8, and 15 of each 28 day study cycle. Napabucasin administration began 2 days prior to the first paclitaxel infusion in the initial run in period.	Placebo + Paclitaxel n=357 Participants Placebo was administered orally, twice daily, with doses separated by 12 hours. Paclitaxel 80 mg/m2 (intravenous \[IV\]) was administered weekly, on Days 1, 8, and 15 of each 28 day study cycle. Placebo administration began 2 days prior to the first paclitaxel infusion in the initial run in period.
Progression Free Survival	3.55 Months Interval 3.22 to 3.68	3.68 Months Interval 3.48 to 3.71

SECONDARY outcome

Timeframe: 36 months

Objective Response Rate is defined as the percentage of patients with a documented complete response or partial response (CR + PR) based on RECIST 1.1.

Outcome measures

Outcome measures
Measure	Napabucasin + Paclitaxel n=289 Participants Napabucasin was administered orally, twice daily, with doses separated by 12 hours. Paclitaxel 80 mg/m2 (intravenous \[IV\]) was administered weekly, on Days 1, 8, and 15 of each 28 day study cycle. Napabucasin administration began 2 days prior to the first paclitaxel infusion in the initial run in period.	Placebo + Paclitaxel n=283 Participants Placebo was administered orally, twice daily, with doses separated by 12 hours. Paclitaxel 80 mg/m2 (intravenous \[IV\]) was administered weekly, on Days 1, 8, and 15 of each 28 day study cycle. Placebo administration began 2 days prior to the first paclitaxel infusion in the initial run in period.
Objective Response Rate	16 Participants	18 Participants

SECONDARY outcome

Timeframe: 36 months

Disease control Rate is defined as the percentage of patients with a documented complete response or partial response (CR + PR+SD) based on RECIST 1.1.

Outcome measures

Outcome measures
Measure	Napabucasin + Paclitaxel n=289 Participants Napabucasin was administered orally, twice daily, with doses separated by 12 hours. Paclitaxel 80 mg/m2 (intravenous \[IV\]) was administered weekly, on Days 1, 8, and 15 of each 28 day study cycle. Napabucasin administration began 2 days prior to the first paclitaxel infusion in the initial run in period.	Placebo + Paclitaxel n=283 Participants Placebo was administered orally, twice daily, with doses separated by 12 hours. Paclitaxel 80 mg/m2 (intravenous \[IV\]) was administered weekly, on Days 1, 8, and 15 of each 28 day study cycle. Placebo administration began 2 days prior to the first paclitaxel infusion in the initial run in period.
Disease Control Rate	55 Participants	58 Participants

SECONDARY outcome

Timeframe: 36 months

All patients who have received at least one dose of BBI608/Placebo will be included in the safety analysis. The number of patients who experienced at least one adverse event is reported.

Outcome measures

Outcome measures
Measure	Napabucasin + Paclitaxel n=357 Participants Napabucasin was administered orally, twice daily, with doses separated by 12 hours. Paclitaxel 80 mg/m2 (intravenous \[IV\]) was administered weekly, on Days 1, 8, and 15 of each 28 day study cycle. Napabucasin administration began 2 days prior to the first paclitaxel infusion in the initial run in period.	Placebo + Paclitaxel n=350 Participants Placebo was administered orally, twice daily, with doses separated by 12 hours. Paclitaxel 80 mg/m2 (intravenous \[IV\]) was administered weekly, on Days 1, 8, and 15 of each 28 day study cycle. Placebo administration began 2 days prior to the first paclitaxel infusion in the initial run in period.
Number of Patients With Adverse Events	352 Participants	338 Participants

Adverse Events

Napabucasin + Paclitaxel

Serious events: 125 serious events

Other events: 352 other events

Deaths: 286 deaths

Placebo + Paclitaxel

Serious events: 101 serious events

Other events: 338 other events

Deaths: 275 deaths

Serious adverse events

Other adverse events

Additional Information

Marilyn Fontaine

Sumitomo Dainippon Pharma Oncology

Phone: 617-674-8556

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	Napabucasin + Paclitaxel n=357 participants at risk Napabucasin was administered orally, twice daily, with doses separated by 12 hours. Paclitaxel 80 mg/m2 (intravenous \[IV\]) was administered weekly, on Days 1, 8, and 15 of each 28 day study cycle. Napabucasin administration began 2 days prior to the first paclitaxel infusion in the initial run in period.	Placebo + Paclitaxel n=350 participants at risk Placebo was administered orally, twice daily, with doses separated by 12 hours. Paclitaxel 80 mg/m2 (intravenous \[IV\]) was administered weekly, on Days 1, 8, and 15 of each 28 day study cycle. Placebo administration began 2 days prior to the first paclitaxel infusion in the initial run in period.
Gastrointestinal disorders Diarrhoea	85.2% 304/357 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.	36.0% 126/350 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.
Gastrointestinal disorders Nausea	49.9% 178/357 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.	35.1% 123/350 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.
Gastrointestinal disorders Abdominal pain	39.2% 140/357 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.	26.6% 93/350 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.
Gastrointestinal disorders Vomiting	37.8% 135/357 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.	27.1% 95/350 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.
Gastrointestinal disorders Constipation	17.1% 61/357 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.	22.3% 78/350 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.
Gastrointestinal disorders Abdominal pain upper	9.8% 35/357 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.	11.4% 40/350 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.
Gastrointestinal disorders Abdominal distension	7.8% 28/357 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.	7.1% 25/350 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.
Gastrointestinal disorders Dysphagia	6.2% 22/357 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.	6.9% 24/350 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.
Gastrointestinal disorders Ascites	5.0% 18/357 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.	4.9% 17/350 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.
General disorders Fatigue	30.8% 110/357 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.	26.3% 92/350 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.
General disorders Asthenia	20.4% 73/357 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.	20.9% 73/350 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.
General disorders Pyrexia	16.0% 57/357 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.	11.4% 40/350 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.
General disorders Oedema peripheral	10.6% 38/357 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.	8.9% 31/350 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.
Metabolism and nutrition disorders Decreased appetite	36.1% 129/357 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.	29.4% 103/350 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.
Metabolism and nutrition disorders Hypokalaemia	8.1% 29/357 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.	2.6% 9/350 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.
Metabolism and nutrition disorders Hypoalbuminaemia	5.6% 20/357 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.	5.1% 18/350 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.
Nervous system disorders Neuropathy peripheral	12.9% 46/357 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.	10.9% 38/350 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.
Nervous system disorders Peripheral sensory neuropathy	10.4% 37/357 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.	13.4% 47/350 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.
Nervous system disorders Dysgeusia	7.6% 27/357 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.	4.3% 15/350 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.
Nervous system disorders Dizziness	5.3% 19/357 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.	5.4% 19/350 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.
Nervous system disorders Paraesthesia	4.8% 17/357 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.	6.3% 22/350 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.
Blood and lymphatic system disorders Anaemia	35.3% 126/357 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.	33.7% 118/350 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.
Blood and lymphatic system disorders Neutropenia	10.4% 37/357 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.	14.0% 49/350 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.
Blood and lymphatic system disorders Leukopenia	6.2% 22/357 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.	5.4% 19/350 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.
Investigations Neutrophil count decreased	13.4% 48/357 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.	15.1% 53/350 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.
Investigations Weight decreased	11.5% 41/357 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.	6.6% 23/350 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.
Investigations White blood cell count decreased	9.8% 35/357 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.	12.3% 43/350 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.
Skin and subcutaneous tissue disorders Alopecia	20.4% 73/357 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.	26.9% 94/350 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.
Infections and infestations Urinary tract infection	8.1% 29/357 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.	3.4% 12/350 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.
Respiratory, thoracic and mediastinal disorders Cough	9.8% 35/357 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.	9.7% 34/350 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.
Respiratory, thoracic and mediastinal disorders Dyspnoea	8.4% 30/357 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.	10.6% 37/350 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.
Renal and urinary disorders Chromaturia	13.2% 47/357 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.	0.86% 3/350 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.
Musculoskeletal and connective tissue disorders Back pain	8.7% 31/357 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.	9.4% 33/350 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.
Musculoskeletal and connective tissue disorders Arthralgia	4.8% 17/357 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.	8.0% 28/350 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.
Psychiatric disorders Insomnia	8.4% 30/357 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.	7.7% 27/350 • Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.