Trial Outcomes & Findings for A Study of Napabucasin Plus Nab-Paclitaxel With Gemcitabine in Adult Patients With Metastatic Pancreatic Adenocarcinoma (NCT NCT02993731)

NCT ID: NCT02993731

Last Updated: 2023-11-15

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1134 participants

Primary outcome timeframe

From 4 weeks after the patient has been off study therapy, every 4 weeks thereafter for 6 months, then every 3 months thereafter until death, the study closes or 3 years since treatment discontinuation.

Results posted on

2023-11-15

Participant Flow

1134 participants were randomized between February 2017 and February 2019.

Patients who died, withdrew consent to survival follow up or were lost to follow up were considered to have completed the study.

Participant milestones

Participant milestones
Measure	Napabucasin Plus Nab-paclitaxel With Gemcitabine All participants who were randomized to Arm 1 to receive napabucasin administered orally, twice daily in combination with weekly nab-paclitaxel and gemcitabine administered intravenously, once weekly, on 3 of every 4 weeks.	Nab-paclitaxel With Gemcitabine All participants who were randomized to Arm 2 to receive nab-paclitaxel and gemcitabine administered intravenously, once weekly, on 3 of every 4 weeks.
Overall Study STARTED	565	569
Overall Study COMPLETED	464	464
Overall Study NOT COMPLETED	101	105

Reasons for withdrawal

Reasons for withdrawal
Measure	Napabucasin Plus Nab-paclitaxel With Gemcitabine All participants who were randomized to Arm 1 to receive napabucasin administered orally, twice daily in combination with weekly nab-paclitaxel and gemcitabine administered intravenously, once weekly, on 3 of every 4 weeks.	Nab-paclitaxel With Gemcitabine All participants who were randomized to Arm 2 to receive nab-paclitaxel and gemcitabine administered intravenously, once weekly, on 3 of every 4 weeks.
Overall Study Study Termination	101	105

Baseline Characteristics

A Study of Napabucasin Plus Nab-Paclitaxel With Gemcitabine in Adult Patients With Metastatic Pancreatic Adenocarcinoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Napabucasin Plus Nab-paclitaxel With Gemcitabine n=565 Participants All participants who were randomized to Arm 1 to receive napabucasin administered orally, twice daily in combination with weekly nab-paclitaxel and gemcitabine administered intravenously, once weekly, on 3 of every 4 weeks.	Nab-paclitaxel With Gemcitabine n=569 Participants All participants who were randomized to Arm 2 to receive nab-paclitaxel and gemcitabine administered intravenously, once weekly, on 3 of every 4 weeks.	Total n=1134 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	325 Participants n=5 Participants	295 Participants n=7 Participants	620 Participants n=5 Participants
Age, Categorical >=65 years	240 Participants n=5 Participants	274 Participants n=7 Participants	514 Participants n=5 Participants
Sex: Female, Male Female	240 Participants n=5 Participants	263 Participants n=7 Participants	503 Participants n=5 Participants
Sex: Female, Male Male	325 Participants n=5 Participants	306 Participants n=7 Participants	631 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	194 Participants n=5 Participants	188 Participants n=7 Participants	382 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	10 Participants n=5 Participants	18 Participants n=7 Participants	28 Participants n=5 Participants
Race (NIH/OMB) White	350 Participants n=5 Participants	354 Participants n=7 Participants	704 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	8 Participants n=7 Participants	19 Participants n=5 Participants

PRIMARY outcome

Timeframe: From 4 weeks after the patient has been off study therapy, every 4 weeks thereafter for 6 months, then every 3 months thereafter until death, the study closes or 3 years since treatment discontinuation.

Outcome measures

Outcome measures
Measure	Napabucasin Plus Nab-paclitaxel With Gemcitabine n=565 Participants All participants who were randomized to Arm 1 to receive napabucasin administered orally, twice daily in combination with weekly nab-paclitaxel and gemcitabine administered intravenously, once weekly, on 3 of every 4 weeks.	Nab-paclitaxel With Gemcitabine n=569 Participants All participants who were randomized to Arm 2 to receive nab-paclitaxel and gemcitabine administered intravenously, once weekly, on 3 of every 4 weeks.
Overall Survival	11.43 Months Interval 10.51 to 12.19	11.73 Months Interval 10.74 to 12.71

SECONDARY outcome

Timeframe: From date of randomization, every 8 weeks, until the date of first documented objective disease progression, up to 36 months

Outcome measures

Outcome measures
Measure	Napabucasin Plus Nab-paclitaxel With Gemcitabine n=565 Participants All participants who were randomized to Arm 1 to receive napabucasin administered orally, twice daily in combination with weekly nab-paclitaxel and gemcitabine administered intravenously, once weekly, on 3 of every 4 weeks.	Nab-paclitaxel With Gemcitabine n=569 Participants All participants who were randomized to Arm 2 to receive nab-paclitaxel and gemcitabine administered intravenously, once weekly, on 3 of every 4 weeks.
Progression Free Survival	6.70 Months Interval 5.68 to 7.26	6.08 Months Interval 5.59 to 7.1

SECONDARY outcome

Timeframe: From date of randomization, every 8 weeks, until the date of first documented objective disease progression, up to 36 months

To assess the effect of napabucasin plus weekly nab-paclitaxel with gemcitabine versus weekly nab-paclitaxel with gemcitabine on the Disease Control Rate (DCR) of patients with metastatic pancreatic ductal adenocarcinoma. DCR is defined as the proportion of patients with a documented complete response, partial response, and stable disease (CR + PR + SD) based on RECIST 1.1.

Outcome measures

Outcome measures
Measure	Napabucasin Plus Nab-paclitaxel With Gemcitabine n=556 Participants All participants who were randomized to Arm 1 to receive napabucasin administered orally, twice daily in combination with weekly nab-paclitaxel and gemcitabine administered intravenously, once weekly, on 3 of every 4 weeks.	Nab-paclitaxel With Gemcitabine n=559 Participants All participants who were randomized to Arm 2 to receive nab-paclitaxel and gemcitabine administered intravenously, once weekly, on 3 of every 4 weeks.
Disease Control Rate	74 Percentage of participants Interval 71.0 to 78.0	76 Percentage of participants Interval 72.0 to 80.0

SECONDARY outcome

Timeframe: From date of randomization, every 8 weeks, until the date of first documented objective disease progression, up to 36 months

To assess the effect of napabucasin plus weekly nab-paclitaxel with gemcitabine versus weekly nab-paclitaxel with gemcitabine on the Overall Response Rate (ORR) of patients with metastatic pancreatic ductal adenocarcinoma. ORR is evaluated using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1).

Outcome measures

Outcome measures
Measure	Napabucasin Plus Nab-paclitaxel With Gemcitabine n=556 Participants All participants who were randomized to Arm 1 to receive napabucasin administered orally, twice daily in combination with weekly nab-paclitaxel and gemcitabine administered intravenously, once weekly, on 3 of every 4 weeks.	Nab-paclitaxel With Gemcitabine n=559 Participants All participants who were randomized to Arm 2 to receive nab-paclitaxel and gemcitabine administered intravenously, once weekly, on 3 of every 4 weeks.
Overall Response Rate	43 Percentage Interval 39.0 to 47.0	43 Percentage Interval 39.0 to 47.0

SECONDARY outcome

Timeframe: Every 1-2 weeks from date of screening until protocol treatment discontinuation. Following permanent protocol treatment discontinuation, every 8 weeks, starting with the 4 week post-protocol treatment discontinuation visit, up to 36 months.

All patients who have received at least one dose of napabucasin will be included in the safety analysis according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) version 4.0. The incidence of adverse events will be summarized by type of adverse event and severity.

Outcome measures

Outcome measures
Measure	Napabucasin Plus Nab-paclitaxel With Gemcitabine n=561 Participants All participants who were randomized to Arm 1 to receive napabucasin administered orally, twice daily in combination with weekly nab-paclitaxel and gemcitabine administered intravenously, once weekly, on 3 of every 4 weeks.	Nab-paclitaxel With Gemcitabine n=547 Participants All participants who were randomized to Arm 2 to receive nab-paclitaxel and gemcitabine administered intravenously, once weekly, on 3 of every 4 weeks.
Number of Patients With Adverse Events	560 Participants	543 Participants

SECONDARY outcome

Timeframe: 8 weeks

Population: Each patient has 1 score selected from questionnaires collected from scheduled and unscheduled visits per scale per analysis window. If a patient had more than 1 questionnaire collected in an analysis window, the one collected closest to the target day is selected; if questionnaires had same days from the target day, the later one is selected; if questionnaires collected from the same date, the worst one is selected.

QoL will be measured using the European Organization for Research and Treatment of Cancer Quality of Life questionnaire (EORTC-QLQ-C30) in patients with metastatic pancreatic ductal adenocarcinoma with napabucasin plus weekly nab-paclitaxel with gemcitabine versus weekly nab-paclitaxel with gemcitabine. EORTQ QLC-C30 is a questionnaire used to assess the overall quality of life in cancer patients - 28 questions use a 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions use a 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged and transformed to 0-100 scale; higher overall score = better quality of life.

Outcome measures

Outcome measures
Measure	Napabucasin Plus Nab-paclitaxel With Gemcitabine n=420 Participants All participants who were randomized to Arm 1 to receive napabucasin administered orally, twice daily in combination with weekly nab-paclitaxel and gemcitabine administered intravenously, once weekly, on 3 of every 4 weeks.	Nab-paclitaxel With Gemcitabine n=430 Participants All participants who were randomized to Arm 2 to receive nab-paclitaxel and gemcitabine administered intravenously, once weekly, on 3 of every 4 weeks.
Mean Change From Baseline for Global Quality of Life (QoL) at 8 Weeks.	-1.63 Score on a scale Standard Deviation 22.535	-0.57 Score on a scale Standard Deviation 23.402

OTHER_PRE_SPECIFIED outcome

To assess the effect of napabucasin plus weekly nab-paclitaxel with gemcitabine versus weekly nab-paclitaxel with gemcitabine on the Overall Survival of patients with metastatic pancreatic ductal adenocarcinoma in biomarker positive patients. This biomarker-positive sub-population is defined as those patients with phospho-STAT3 positivity based on immunohistochemical (IHC) staining of Formalin Fixed Paraffin Embedded (FFPE) tumor tissue.

Outcome measures

Outcome measures
Measure	Napabucasin Plus Nab-paclitaxel With Gemcitabine n=206 Participants All participants who were randomized to Arm 1 to receive napabucasin administered orally, twice daily in combination with weekly nab-paclitaxel and gemcitabine administered intravenously, once weekly, on 3 of every 4 weeks.	Nab-paclitaxel With Gemcitabine n=176 Participants All participants who were randomized to Arm 2 to receive nab-paclitaxel and gemcitabine administered intravenously, once weekly, on 3 of every 4 weeks.
Overall Survival in Biomarker Positive Patients	11.40 Months Interval 10.02 to 12.42	10.78 Months Interval 9.4 to 12.55

OTHER_PRE_SPECIFIED outcome

Timeframe: From date of randomization, every 8 weeks, until the date of first documented objective disease progression, up to 36 months

To assess the effect of napabucasin plus weekly nab-paclitaxel with gemcitabine versus weekly nab-paclitaxel with gemcitabine on the Progression Free Survival (PFS) of patients with metastatic pancreatic ductal adenocarcinoma in biomarker positive patients. PFS is defined as the time from randomization to the first objective documentation of disease progression or death due to any cause. This biomarker-positive sub-population is defined as those patients with phospho-STAT3 positivity based on immunohistochemical (IHC) staining of Formalin Fixed Paraffin Embedded (FFPE) tumor tissue.

Outcome measures

Outcome measures
Measure	Napabucasin Plus Nab-paclitaxel With Gemcitabine n=206 Participants All participants who were randomized to Arm 1 to receive napabucasin administered orally, twice daily in combination with weekly nab-paclitaxel and gemcitabine administered intravenously, once weekly, on 3 of every 4 weeks.	Nab-paclitaxel With Gemcitabine n=176 Participants All participants who were randomized to Arm 2 to receive nab-paclitaxel and gemcitabine administered intravenously, once weekly, on 3 of every 4 weeks.
Progression Free Survival in Biomarker Positive Patients	5.68 Months Interval 5.49 to 7.39	5.82 Months Interval 5.55 to 7.29

OTHER_PRE_SPECIFIED outcome

Timeframe: From date of randomization, every 8 weeks, until the date of first documented objective disease progression, up to 36 months

To assess the effect of napabucasin plus weekly nab-paclitaxel with gemcitabine versus weekly nab-paclitaxel with gemcitabine on the Disease Control Rate (DCR) of patients with metastatic pancreatic ductal adenocarcinoma in biomarker positive patients. DCR is evaluated using RECIST 1.1. This biomarker-positive sub-population is defined as those patients with phospho-STAT3 positivity based on immunohistochemical (IHC) staining of Formalin Fixed Paraffin Embedded (FFPE) tumor tissue.

Outcome measures

Outcome measures
Measure	Napabucasin Plus Nab-paclitaxel With Gemcitabine n=203 Participants All participants who were randomized to Arm 1 to receive napabucasin administered orally, twice daily in combination with weekly nab-paclitaxel and gemcitabine administered intravenously, once weekly, on 3 of every 4 weeks.	Nab-paclitaxel With Gemcitabine n=173 Participants All participants who were randomized to Arm 2 to receive nab-paclitaxel and gemcitabine administered intravenously, once weekly, on 3 of every 4 weeks.
Disease Control Rate in Biomarker Positive Patients	75 Percentage Interval 69.0 to 81.0	79 Percentage Interval 72.0 to 84.0

OTHER_PRE_SPECIFIED outcome

Timeframe: From date of randomization, every 8 weeks, until the date of first documented objective disease progression, up to 36 months

To assess the effect of napabucasin plus weekly nab-paclitaxel with gemcitabine versus weekly nab-paclitaxel with gemcitabine on the Overall Response Rate (ORR) of patients with metastatic pancreatic ductal adenocarcinoma in biomarker positive patients. ORR is evaluated using RECIST 1.1. This biomarker-positive sub-population is defined as those patients with phospho-STAT3 positivity based on immunohistochemical (IHC) staining of Formalin Fixed Paraffin Embedded (FFPE) tumor tissue.

Outcome measures

Outcome measures
Measure	Napabucasin Plus Nab-paclitaxel With Gemcitabine n=203 Participants All participants who were randomized to Arm 1 to receive napabucasin administered orally, twice daily in combination with weekly nab-paclitaxel and gemcitabine administered intravenously, once weekly, on 3 of every 4 weeks.	Nab-paclitaxel With Gemcitabine n=173 Participants All participants who were randomized to Arm 2 to receive nab-paclitaxel and gemcitabine administered intravenously, once weekly, on 3 of every 4 weeks.
Overall Response Rate in Biomarker Positive Patients	42 Percentage Interval 35.0 to 49.0	47 Percentage Interval 40.0 to 55.0

Adverse Events

Napabucasin Plus Nab-paclitaxel With Gemcitabine (Safety Population)

Serious events: 330 serious events

Other events: 560 other events

Deaths: 419 deaths

Nab-paclitaxel With Gemcitabine (Safety Population)

Serious events: 273 serious events

Other events: 543 other events

Deaths: 400 deaths

Serious adverse events

Other adverse events

Additional Information

Cindy Oh

Sumitomo Dainippon Pharma Oncology

Phone: 617-674-8628

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The primary author agrees to, prior to submitting a manuscript, abstract, or any other written/oral presentation describing the Results for publication/presentation, forward a copy to the Sponsor at least 45 days prior to their submission. The Sponsor may request an additional 30-day embargo. The Sponsor may require the primary author to delete any Confidential Information (other than the Clinical Results) and to require that any publication/presentation acknowledge the Sponsor's support.
Publication restrictions are in place

Restriction type: OTHER