Metastatic Pancreatic CancerPhase 2NCT03261947
A Study to Evaluate the Safety, Tolerability, and Activity of TAK-931 in Participants With Metastatic Pancreatic Cancer, Metastatic Colorectal Cancer, and Other Advanced Solid Tumors
A Phase 2 study testing TAK-931 in people with Metastatic Pancreatic Cancer and Colorectal Cancer, run by Millennium Pharmaceuticals, Inc. at 10 sites in 2 countries.
Trial summary
The purpose of this study is to confirm the safety and tolerability of TAK-931 in a cohort of Western participants with metastatic solid tumors and to evaluate the anti-tumor activity of TAK-931 in participants with metastatic pancreatic cancer, colorectal cancer (CRC), squamous esophageal cancer (sqEC), and squamous… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Pancreatic Cancer, Colorectal Cancer, Esophageal Neoplasms
- What is being tested?
- TAK-931
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 101 participants
- Where
- 10 sitesin 2 countries
- Study dates
- 25 Oct 2017to 24 Aug 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult male or female participants aged >=20 years (Japan) or >=18 years (United States).
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- Has pathologically confirmed metastatic pancreatic adenocarcinoma that has progressed after, at least, a first line of standard systemic chemotherapy for the metastatic disease, OR participants with pathologically confirmed metastatic adenocarcinoma of the colon or rectum who have progressed to at least 2 lines of standard systemic chemotherapy for the metastatic disease, OR participants with pathologically confirmed locally advanced or metastatic sqEC that has progressed after at least a first line of standard systemic therapy for metastatic disease. First-line participants can be enrolled if a platinum doublet is contraindicated or refused by the participants, OR pathologically confirmed locally advanced or metastatic sqNSCLC that has progressed after at least 2 lines of standard systemic therapy for metastatic disease.
- For the Western safety cohort only: participants with locally advanced or metastatic solid tumor for whom no standard treatment with an established survival benefit is available or if the participant refuses other standard therapy.
- For disease-specific cohort participants: measurable disease per RECIST v. 1.1
- Left ventricular ejection fraction greater than (>) 50% as measured by ECHO or MUGA scan within 4 weeks before receiving the first dose of study drug.
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- Recovered to Grade 1 or baseline from all toxic effects of previous therapy (except alopecia or neuropathy).
- Suitable venous access for the study-required blood sampling.
- For the Western safety cohort only: willingness to undergo serial skin tissue biopsies.
- For disease-specific cohort participants: Must have an archival (banked) tumor sample or agree to have a new (fresh) tumor biopsy during the screening period. If a new tumor sample is needed, the disease should be accessible for a nonsignificant risk biopsy procedure (those occurring outside the brain, lung/mediastinum, and pancreas, or obtained with endoscopic procedures not extending beyond the stomach or bowel). For participants in the Western safety cohort, this biopsy is optional.
Who cannot join
- Participants who require continuous use of proton pump inhibitors (PPIs) or histamine-2 (H2) receptor antagonists and participants who are taking PPIs within 5 days before the first dose of study drug.
- Treatment with clinically significant enzyme inducers, such as phenytoin, carbamazepine, phenobarbital, rifampin, rifabutin, rifapentine, or Saint John's wort within 14 days before the first dose of study drug.
- Treatment with any systemic anticancer treatment (including investigational products) within 30 days or 5 half-lives, whichever is shorter, before the first dose of study drug.
- History of any of the following within the last 3 months before administration of the first dose of study drug:
- Ischemic myocardial event including angina requiring therapy and artery revascularization procedures, myocardial infarction, and unstable symptomatic ischemic heart disease.
- Ischemic cerebrovascular event, including transient ischemic attack and artery, revascularization procedures.
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- Significant, uncontrolled cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation, or ventricular tachycardia).
- New York Heart Association Class III to IV heart failure.
- Any other cardiac condition that, in the opinion of the investigator, could pose an additional risk for participation in the study (example, pericardial effusion or restrictive cardiomyopathy).
- Baseline prolongation of the QT interval corrected for heart rate (HR) using Fridericia's formula [QT interval corrected for heart rate using Fridericia's formula (QTcF); example, repeated demonstration of QTcF interval >480 millisecond (ms), history of congenital long QT syndrome, or torsades de pointes].
- Hypertension that is unstable or not controlled by medication.
- History of uncontrolled brain metastasis unless:
- Previously treated with surgery, whole-brain radiation, or stereotactic radiosurgery, and
- Stable disease (SD) for >=30 days, without steroid use (or stable steroid dose established for >=14 days before the first dose of TAK-931).
- Known history of human immunodeficiency virus infection.
- Known hepatitis B virus (HBV) surface antigen seropositive or detectable hepatitis C virus (HCV) infection viral load. Note: Participants who have positive HBV core antibody or HBV surface antigen antibody can be enrolled but must have an undetectable HBV viral load.
- Prior treatment with radiation therapy involving >=25% of the hematopoietically active bone marrow within 3 months before the first dose of study drug.
- Participants with known microsatellite instability-high (MSI-H) genotype or known wild type tumor protein 53 (TP53) per local testing.
- Western Safety Cohort Only: Participants with Japanese heredity.
Trial locations and contacts
10 sites in 2 countries.
10 sites in 2 countries
United States8 sites
Sarah Cannon Research Institute Oncology Research Consortium
Denver, Colorado, 80218
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, 89119
Allina Health Virginia Piper Cancer Institute
Minneapolis, Minnesota, 55404
SCRI - Tennessee Oncology - Nashville - Southern Hills Clinic
Nashville, Tennessee, 37203
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Sarah Cannon Research Institute
Sarasota, Florida, 34232
Virginia Mason Medical Center
Seattle, Washington, 98101-2756
Siteman Cancer Center
St Louis, Missouri, 63110
Japan2 sites
National Cancer Center Hospital
Chuo-ku, Tokyo, 104-0045
National Cancer Center Hospital East
Kashiwa, Chiba, 277-8577
About this study
Official title: An Open-Label, Phase 2, Parallel Arm Study to Evaluate the Safety, Tolerability, and Activity of TAK-931 Single Agent in Patients With Metastatic Pancreatic Cancer, Metastatic Colorectal Cancer, and Other Advanced Solid Tumors
The purpose of this study is to confirm the safety and tolerability of TAK-931 in a cohort of Western participants with metastatic solid tumors and to evaluate the anti-tumor activity of TAK-931 in participants with metastatic pancreatic cancer, colorectal cancer (CRC), squamous esophageal cancer (sqEC), and squamous non-small-cell lung cancer (sqNSCLC).
Read the detailed description
Pancreatic Arm Now Closed.
The drug being tested in this study is called TAK-931. TAK-931 blocks function of a specific protein called CDC7 kinase in the human body. TAK-931 is being tested in participants with metastatic cancer (colorectal, pancreatic, sqNSCLC and sqEC) in the United States and Japan and also in the participants with any type of metastatic cancer with no standard therapeutic alternative in the United States only. This study will look at the safety, tolerability and pharmacokinetics of TAK-931.
The study will enroll approximately 160 participants. Participants will be enrolled in 5 cohorts: 1) Western safety cohort, to be enrolled in the United States only, will include non-Japanese participants with metastatic solid tumors and no standard therapeutic alternative, 2) Metastatic pancreatic cancer cohort, 3) Metastatic colorectal cancer cohort, 4) Metastatic sqNSCLC cohort, and 5) Metastatic sqEC cohort. All participants will receive:
- TAK-931 50 mg (2x25 mg or 5x10 mg) capsules
All participants will be asked to take one 50 mg (2x25 mg or 5x10 mg) capsule at the same time of the day every day for 14 days, followed by 7 days break in 21-day cycles throughout the study.
This multi-center trial will be conducted in the United States and Japan. The overall time to participate in this study is approximately 24 months. Participants will make multiple visits to the clinic. Participants in both Western cohort and disease specific cohorts will be followed for progression-free survival every 12 weeks after the last dose of the study drug until the occurrence of disease progression, loss to follow up, consent withdrawal, death, start of subsequent antineoplastic therapy, study termination, or until 6 months after discontinuation of the study treatment, whichever occurs first. Once disease progression is confirmed, participants in the disease-specific cohorts will be followed for overall survival every 12 weeks until death, loss to follow up, consent withdrawal, study termination, or transfer of a participant to a long term safety study, single participant investigational new drug application, or similar program after the last dose of the study drug.
- Conditions
- Metastatic Pancreatic Cancer, Colorectal Cancer, Esophageal Neoplasms, Carcinoma, Non-small-cell Lung
- Being tested
- TAK-931
- Keywords
- Drug therapy
- Medical subject headings
- Pancreatic Neoplasms, Colorectal Neoplasms, Esophageal Neoplasms, Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TAK-931Drug
TAK-931 hard gelatin capsules
| Study group | Role | What they receive |
|---|---|---|
| Western Safety Cohort | Experimental | TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, once daily (QD) for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 20 cycles. Participants with locally advanced or metastatic solid tumors with no standard therapeutic alternative in the United States were included in this cohort. Receives: Drug: TAK-931 |
| Pancreatic Cancer Cohort | Experimental | TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 4 cycles. Participants with metastatic pancreatic cancer who had progressed after at least 1 line of standard chemotherapy were included in this cohort. Receives: Drug: TAK-931 |
| Metastatic CRC Cohort | Experimental | TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 12 cycles. Participants with metastatic CRC who had progressed after at least 2 lines of previous standard chemotherapy were included in this cohort. Receives: Drug: TAK-931 |
| sqEC Cohort | Experimental | TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 8 cycles. Participants with metastatic sqEC who had progressed after at least 1 line of standard chemotherapy were included in this cohort. Receives: Drug: TAK-931 |
| sqNSCLC Cohort | Experimental | TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort. Receives: Drug: TAK-931 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Dose Limiting Toxicities (DLTs) in Western Safety Cohort
DLT:Any following event related to TAK-931 assessed by Common Terminology Criteria for Adverse Events(CTCAE) version4.03;Non-febrile Grade 4 neutropenia; febrile neutropenia: Grade >=3 neutropenia; Grade4 thrombocytopenia; Grade >=3 thrombocytopenia of any duration accompanied by Grade 2 bleeding or requiring transfusion; delay in initiation of Cycle 2 by >14 days due to lack of adequate recovery of treatment-related hematological or nonhematologic toxicities; Grade 2 ejection fraction decreased by echocardiogram(ECHO) or multiple gated acquisition(MUGA) scan; Grade 4 laboratory abnormalities; other Grade 2 nonhematologic toxicities considered by investigator to be related to study drug and dose-limiting; Participants receiving <50% of doses (<7 doses) of planned TAK-931 dosing in Cycle 1 due to study drug-related adverse events(AEs); Grade >=3 nonhematologic toxicity with few exceptions: Grade 3 arthralgia/myalgia, fatigue, laboratory abnormalities, nausea and/or emesis or diarrhea.
Measured: Cycle 1 (each cycle = 21 days)
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), TEAEs Leading to Dose Modifications and TEAEs Leading to Treatment Discontinuation in Western Safety Cohort
An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE was defined as an adverse event with an onset that occurred after receiving study drug. An SAE was any untoward medical occurrence or effect that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was medically important due to other reasons than the above mentioned criteria.
Measured: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months)
Disease Control Rate (DCR) in Tumor-Specific Cohorts
DCR was defined as percentage of participants documented to have unconfirmed CR, PR, or SD for at least 6 weeks from treatment initiation according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as the best response. CR was defined as disappearance of all lesions. PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of lesions, taking as reference the baseline sum LD. Stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum LD since the treatment started. PD was defined as at least a 20% increase in the sum of the LD of lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Measured: From first dose up to end of treatment (Up to approximately 14 months)
Secondary outcomes (15)
Cmax: Maximum Observed Plasma Concentration for TAK-931
Measured: Cycle 1 (each cycle = 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-931
Measured: Cycle 1 (each cycle = 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose
AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-931
Measured: Cycle 1 (each cycle = 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose
AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-931
Measured: Cycle 1 (each cycle = 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose
CLr: Renal Clearance of TAK-931
CLr is a measure of apparent clearance of the drug from the plasma, renal clearance is a measure of drug excreted through kidneys/urine per unit time.
Measured: Cycle 1 (each cycle = 21 days) Day 1 pre-dose and at multiple timepoints (up to 8 hours urine sampling) post-dose
t1/2z: Terminal Disposition Phase Half-life for TAK-931
Measured: Cycle 1 (each cycle = 21 days) Day 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose
CLss/F: Steady-state Apparent Oral Clearance for TAK-931
CL/F was defined as apparent clearance of the drug from the plasma, calculated as the drug dose divided by AUC.
Measured: Cycle 1 (each cycle = 21 days) Day 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose
Rac(AUC): Accumulation Ratio Based on AUC Over the Dosing Interval (AUCτ) for TAK-931
Measured: Cycle 1 (each cycle = 21 days) Day 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose
Overall Response Rate (CR and PR)
Overall response rate was defined as percentage of participants documented to have unconfirmed CR or PR according to RECIST v1.1 as the best response. CR was defined as disappearance of all lesions, PR was defined as at least a 30% decrease in the sum of the LD of lesions, taking as reference the baseline sum LD.
Measured: From first dose up to end of treatment (Up to approximately 14 months)
Duration of Response (DOR)
DOR was defined as the time from the date of first documentation of a CR or PR to the date of first documentation of tumor progression. Per RECIST V1.1, CR was defined as disappearance of all lesions, PR was defined as at least a 30% decrease in the sum of the LD of lesions, taking as reference the baseline sum LD. PD was defined as at least a 20% increase in the sum of the LD of lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Measured: From first documented response until disease progression or end of treatment, whichever occurs first (Up to 14 months)
Progression Free Survival (PFS)
PFS was defined as the time from the date of first dose to the date of first documentation of PD (including clinical progression or clinical deterioration) or death due to any cause, whichever occurs first. Per RECIST V1.1, PD was defined as at least a 20% increase in the sum of the LD of lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Measured: From date of randomization until disease progression or death, whichever occurs first (Up to approximately 34 months)
Overall Survival (OS) in the Tumor-Specific Cohorts
OS was defined as the time from the date of first dose of study drug to death due to any cause.
Measured: Up to approximately 43 months
Percentage of Participants With Grade >=3 TEAEs, SAEs, TEAEs Leading to Dose Modifications, and TEAEs Leading to Treatment Discontinuation in Tumor-Specific Cohorts
An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it did not necessarily have to have a causal relationship with this treatment. A TEAE was defined as an adverse event with an onset that occurred after receiving study drug. TEAEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.03, where Grade 3: Severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated; Grade 4:Life-threatening consequences, urgent intervention indicated; Grade 5:Death related to AE. An SAE was any untoward medical occurrence or effect that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was medically important due to other reasons than the above mentioned criteria.
Measured: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months)
Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts
Clinical laboratory tests included hematology, clinical chemistry and urinalysis. The investigator determined if the results were clinically significant. Only those categories were reported which are clinically significant at post Baseline.
Measured: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months)
Percentage of Participants With Clinically Significant Changes in Vital Sign Measurements, Reported as Adverse Events in Tumor-Specific Cohorts
Vital signs included assessments of systolic and diastolic blood pressure (BP), heart rate (HR), and body temperature. The investigator determined if the results were clinically significant. Only those categories were reported which are clinically significant at post Baseline.
Measured: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2017
- Study start25 Oct 2017
- Primary completion24 Aug 2020
- Study completion24 Aug 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Metastatic Pancreatic CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 101 participants (actual)
Sponsor and investigators
- Lead sponsor
- Millennium Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03261947
- Sponsor's protocol ID
- TAK-931-2001
- Other IDs
- U1111-1192-7975, JapicCTI-163200
- Status last verified
- Aug 2021
- First submitted
- 23 Aug 2017
- Last updated
- 20 Sep 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
Study at a glance
From the registry record, last updated by the sponsor on 20 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Phase 2, Parallel Arm Study to Evaluate the Safety, Tolerability, and Activity of TAK-931 Single Agent in Patients With Metastatic Pancreatic Cancer, Metastatic Colorectal Cancer, and Other Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT03261947
- Acronym / sponsor ID
- TAK-931-2001
- Conditions
- Metastatic Pancreatic Cancer, Colorectal Cancer, Esophageal Neoplasms, Carcinoma, Non-small-cell Lung
- Keywords
- Drug therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 101 participants (actual)
- Lead sponsor
- Millennium Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 25 Oct 2017 (actual)
- Primary completion
- 24 Aug 2020 (actual)
- Study completion
- 24 Aug 2020 (actual)
- First posted
- 25 Aug 2017 (actual)
- Results
- Posted 20 Sep 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to confirm the safety and tolerability of TAK-931 in a cohort of Western participants with metastatic solid tumors and to evaluate the anti-tumor activity of TAK-931 in participants with metastatic pancreatic cancer, colorectal cancer (CRC), squamous esophageal cancer (sqEC), and squamous non-small-cell lung cancer (sqNSCLC).
Detailed description
Pancreatic Arm Now Closed.
The drug being tested in this study is called TAK-931. TAK-931 blocks function of a specific protein called CDC7 kinase in the human body. TAK-931 is being tested in participants with metastatic cancer (colorectal, pancreatic, sqNSCLC and sqEC) in the United States and Japan and also in the participants with any type of metastatic cancer with no standard therapeutic alternative in the United States only. This study will look at the safety, tolerability and pharmacokinetics of TAK-931.
The study will enroll approximately 160 participants. Participants will be enrolled in 5 cohorts: 1) Western safety cohort, to be enrolled in the United States only, will include non-Japanese participants with metastatic solid tumors and no standard therapeutic alternative, 2) Metastatic pancreatic cancer cohort, 3) Metastatic colorectal cancer cohort, 4) Metastatic sqNSCLC cohort, and 5) Metastatic sqEC cohort. All participants will receive:
- TAK-931 50 mg (2x25 mg or 5x10 mg) capsules
All participants will be asked to take one 50 mg (2x25 mg or 5x10 mg) capsule at the same time of the day every day for 14 days, followed by 7 days break in 21-day cycles throughout the study.
This multi-center trial will be conducted in the United States and Japan. The overall time to participate in this study is approximately 24 months. Participants will make multiple visits to the clinic. Participants in both Western cohort and disease specific cohorts will be followed for progression-free survival every 12 weeks after the last dose of the study drug until the occurrence of disease progression, loss to follow up, consent withdrawal, death, start of subsequent antineoplastic therapy, study termination, or until 6 months after discontinuation of the study treatment, whichever occurs first. Once disease progression is confirmed, participants in the disease-specific cohorts will be followed for overall survival every 12 weeks until death, loss to follow up, consent withdrawal, study termination, or transfer of a participant to a long term safety study, single participant investigational new drug application, or similar program after the last dose of the study drug.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Western Safety Cohort | Experimental | Drug: TAK-931TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, once daily (QD) for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 20 cycles. Participants with locally advanced or metastatic solid tumors with no standard therapeutic alternative in the United States were included in this cohort. |
| Pancreatic Cancer Cohort | Experimental | Drug: TAK-931TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 4 cycles. Participants with metastatic pancreatic cancer who had progressed after at least 1 line of standard chemotherapy were included in this cohort. |
| Metastatic CRC Cohort | Experimental | Drug: TAK-931TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 12 cycles. Participants with metastatic CRC who had progressed after at least 2 lines of previous standard chemotherapy were included in this cohort. |
| sqEC Cohort | Experimental | Drug: TAK-931TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 8 cycles. Participants with metastatic sqEC who had progressed after at least 1 line of standard chemotherapy were included in this cohort. |
| sqNSCLC Cohort | Experimental | Drug: TAK-931TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Adult male or female participants aged >=20 years (Japan) or >=18 years (United States).
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- Has pathologically confirmed metastatic pancreatic adenocarcinoma that has progressed after, at least, a first line of standard systemic chemotherapy for the metastatic disease, OR participants with pathologically confirmed metastatic adenocarcinoma of the colon or rectum who have progressed to at least 2 lines of standard systemic chemotherapy for the metastatic disease, OR participants with pathologically confirmed locally advanced or metastatic sqEC that has progressed after at least a first line of standard systemic therapy for metastatic disease. First-line participants can be enrolled if a platinum doublet is contraindicated or refused by the participants, OR pathologically confirmed locally advanced or metastatic sqNSCLC that has progressed after at least 2 lines of standard systemic therapy for metastatic disease.
- For the Western safety cohort only: participants with locally advanced or metastatic solid tumor for whom no standard treatment with an established survival benefit is available or if the participant refuses other standard therapy.
- For disease-specific cohort participants: measurable disease per RECIST v. 1.1
Key exclusion criteria (19 listed)
- Participants who require continuous use of proton pump inhibitors (PPIs) or histamine-2 (H2) receptor antagonists and participants who are taking PPIs within 5 days before the first dose of study drug.
- Treatment with clinically significant enzyme inducers, such as phenytoin, carbamazepine, phenobarbital, rifampin, rifabutin, rifapentine, or Saint John's wort within 14 days before the first dose of study drug.
- Treatment with any systemic anticancer treatment (including investigational products) within 30 days or 5 half-lives, whichever is shorter, before the first dose of study drug.
- History of any of the following within the last 3 months before administration of the first dose of study drug:
- Hypertension that is unstable or not controlled by medication.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TAK-931TAK-931 hard gelatin capsules | Drug | Metastatic CRC Cohort, Pancreatic Cancer Cohort, Western Safety Cohort, sqEC Cohort, sqNSCLC Cohort |
Primary outcome
Percentage of Participants With Dose Limiting Toxicities (DLTs) in Western Safety Cohort
Time frame: Cycle 1 (each cycle = 21 days)
DLT:Any following event related to TAK-931 assessed by Common Terminology Criteria for Adverse Events(CTCAE) version4.03;Non-febrile Grade 4 neutropenia; febrile neutropenia: Grade >=3 neutropenia; Grade4 thrombocytopenia; Grade >=3 thrombocytopenia of any duration accompanied by Grade 2 bleeding or requiring transfusion; delay in initiation of Cycle 2 by >14 days due to lack of adequate recovery of treatment-related hematological or nonhematologic toxicities; Grade 2 ejection fraction decreased by echocardiogram(ECHO) or multiple gated acquisition(MUGA) scan; Grade 4 laboratory abnormalities; other Grade 2 nonhematologic toxicities considered by investigator to be related to study drug and dose-limiting; Participants receiving <50% of doses (<7 doses) of planned TAK-931 dosing in Cycle 1 due to study drug-related adverse events(AEs); Grade >=3 nonhematologic toxicity with few exceptions: Grade 3 arthralgia/myalgia, fatigue, laboratory abnormalities, nausea and/or emesis or diarrhea.
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), TEAEs Leading to Dose Modifications and TEAEs Leading to Treatment Discontinuation in Western Safety Cohort
Time frame: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months)
An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE was defined as an adverse event with an onset that occurred after receiving study drug. An SAE was any untoward medical occurrence or effect that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was medically important due to other reasons than the above mentioned criteria.
Disease Control Rate (DCR) in Tumor-Specific Cohorts
Time frame: From first dose up to end of treatment (Up to approximately 14 months)
DCR was defined as percentage of participants documented to have unconfirmed CR, PR, or SD for at least 6 weeks from treatment initiation according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as the best response. CR was defined as disappearance of all lesions. PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of lesions, taking as reference the baseline sum LD. Stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum LD since the treatment started. PD was defined as at least a 20% increase in the sum of the LD of lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
15 secondary outcomes
Cmax: Maximum Observed Plasma Concentration for TAK-931
Time frame: Cycle 1 (each cycle = 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-931
Time frame: Cycle 1 (each cycle = 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose
AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-931
Time frame: Cycle 1 (each cycle = 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose
AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-931
Time frame: Cycle 1 (each cycle = 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose
CLr: Renal Clearance of TAK-931
Time frame: Cycle 1 (each cycle = 21 days) Day 1 pre-dose and at multiple timepoints (up to 8 hours urine sampling) post-dose
t1/2z: Terminal Disposition Phase Half-life for TAK-931
Time frame: Cycle 1 (each cycle = 21 days) Day 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose
CLss/F: Steady-state Apparent Oral Clearance for TAK-931
Time frame: Cycle 1 (each cycle = 21 days) Day 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose
Rac(AUC): Accumulation Ratio Based on AUC Over the Dosing Interval (AUCτ) for TAK-931
Time frame: Cycle 1 (each cycle = 21 days) Day 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose
Overall Response Rate (CR and PR)
Time frame: From first dose up to end of treatment (Up to approximately 14 months)
Duration of Response (DOR)
Time frame: From first documented response until disease progression or end of treatment, whichever occurs first (Up to 14 months)
Progression Free Survival (PFS)
Time frame: From date of randomization until disease progression or death, whichever occurs first (Up to approximately 34 months)
Overall Survival (OS) in the Tumor-Specific Cohorts
Time frame: Up to approximately 43 months
Percentage of Participants With Grade >=3 TEAEs, SAEs, TEAEs Leading to Dose Modifications, and TEAEs Leading to Treatment Discontinuation in Tumor-Specific Cohorts
Time frame: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months)
Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts
Time frame: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months)
Percentage of Participants With Clinically Significant Changes in Vital Sign Measurements, Reported as Adverse Events in Tumor-Specific Cohorts
Time frame: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Sep 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Takeda
10 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing TAK-931 in people with Metastatic Pancreatic Cancer and Colorectal Cancer, run by Millennium Pharmaceuticals, Inc. at 10 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States, Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Sep 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Dose Limiting Toxicities (DLTs) in Western Safety Cohort (time frame: Cycle 1 (each cycle = 21 days)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Sep 2021.