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2018-04-23
2020-02-27
2020-02-27
31
NCT03449030
Takeda
Takeda
INTERVENTIONAL
A Study of TAK-164 in Participants With Advanced Gastrointestinal (GI) Cancer Expressing Guanylyl Cyclase C (GCC)
The purpose of this study is to evaluate the safety of TAK-164 and to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) and schedule.
The drug being tested in this study is a novel antibody-drug conjugate (ADC) called TAK-164. TAK-164 is being evaluated in participants with advanced GCC-positive GI cancer (Part A) or colorectal carcinoma (CRC) and gastric carcinoma (Part B and Part C) to determine safety, tolerability, and pharmacokinetics (PK) and MTD/RP2D of TAK-164, as well as the preliminary efficacy. The study will include approximately 100 evaluable participants. In Part A (Escalation), approximately 25 participants with GI carcinoma will be enrolled. Those include participants with various GI malignancies such as carcinomas of esophagus, stomach, colon, and pancreas. The starting dose for Arm 1 will be 0.004 mg/kg of TAK-164 administered intravenously on Day 1 Q3W and the maximal dose will not exceed 0.19 mg/kg Q3W. In Part B (Expansion), approximately 50 participants will be enrolled to receive TAK-164 infusion at determined RP2D in Part A. Participants will follow the Q3W schedule and will be followed until PD, unacceptable toxicity, or until they choose to withdraw consent. In Part C (Imaging substudy to be conducted in the Netherlands only), approximately 25 participants with GCC-expressing metastatic colorectal carcinoma (mCRC) will be enrolled to receive 89Zr-TAK-164 and unlabeled TAK-164 at determined RP2D in Part A. This multi-center trial will be conducted in the United States and the Netherlands. The overall time to participate in this study is up to 55 months. Participants will attend an end of study (EOS) visit 30 days after the last dose of TAK-164 or just prior to the start of subsequent antineoplastic therapy, whichever occurs first.
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
| Study Registration Dates | Results Reporting Dates | Study Record Updates |
|---|---|---|
2018-02-22 | 2021-02-24 | 2021-02-24 |
2018-02-22 | 2021-02-24 | 2021-03-22 |
2018-02-28 | 2021-03-22 | 2021-02 |
This section provides details of the study plan, including how the study is designed and what the study is measuring.
Primary Purpose:
Other
Allocation:
Non Randomized
Interventional Model:
Sequential
Masking:
None
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
|---|---|
| EXPERIMENTAL: Part A Escalation Stage: TAK-164 Q3W TAK-164 0.004 milligram per kilogram (mg/kg) starting dose, intravenous infusion, until PD, unacceptable toxicity or discontinuation by participant. Dose escalation will be performed to determine the MTD and/or RP2D. | DRUG: TAK-164
|
| EXPERIMENTAL: Part B Expansion Stage: TAK-164 Q3W TAK-164, intravenous infusion, until PD, unacceptable toxicity or discontinuation by participant. TAK-164 RP2D dose to be decided based on safety, PK, pharmacodynamics and antitumor response data observed in Part A escalation stage. | DRUG: TAK-164
|
| EXPERIMENTAL: Part C Imaging Substudy: 89Zr-TAK-164 and TAK-164 89Zr-TAK-164, intravenous infusion, followed by unlabeled TAK-164, intravenous infusion in combination with 89Zr-TAK-164, intravenous infusion, and further followed by unlabeled TAK-164, intravenous infusion, until PD, unacceptable toxicity or discontinua | DRUG: TAK-164
DRUG: 89Zr-TAK-164
|
| Primary Outcome Measures | Measure Description | Time Frame |
|---|---|---|
| Number of Participants With Dose-limiting Toxicities (DLTs) | DLTs were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5. DLT was defined as any of the following adverse events (AEs) that occurred and were considered by the investigator to be related to therapy with study drug: hematologic toxicities were, Grade 4 neutropenia (absolute neutrophil count [ANC] less than (<) 500 cells/cubic millimeter [mm^3]), thrombocytopenia (platelets <25,000/mm^3), febrile neutropenia (ANC <1000/mm^3) with fever (greater than [>] 38.3 degree Celsius or sustained temperature of greater than or equal to (>=) 38 degree Celsius, Grade 3 or greater thrombocytopenia with clinically meaningful bleeding at any time, Grade 3 or greater nausea and/or emesis that occurs despite the use of optimal anti-emetic prophylaxis and Grade 3 or greater diarrhea that occurs despite optimal supportive care measures and any other Grade 3 or greater nonhematologic toxicity except brief (<1 week) Grade 3 fatigue. | Baseline up to Month 22 |
| Percentage of Participants With Adverse Events (AEs) | From first dose of study drug up to 30 days following the last dose of study drug (up to 22 months) | |
| Percentage of Participants With Grade 3 or Above AEs | AE Grades were evaluated as per NCI CTCAE, version 5. Graded from Grade 1: Mild asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated, Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL), Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL, Grade 4: Life-threatening consequences; urgent intervention indicated, Grade 5: Death related AE. Higher grade indicates more severe condition. | From first dose of study drug up to 30 days following the last dose of study drug (up to 22 months) |
| Percentage of Participants With Drug-related AEs | From first dose of study drug up to 30 days following the last dose of study drug (up to 22 months) | |
| Percentage of Participants With Drug-related Grade 3 or Above AEs | AE Grades were evaluated as per NCI CTCAE, version 5. Graded from Grade 1: mild asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated, Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL, Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL, Grade 4: Life-threatening consequences; urgent intervention indicated, Grade 5: death related AE. Higher grade indicates more severe condition. | From first dose of study drug up to 30 days following the last dose of study drug (up to 22 months) |
| Percentage of Participants With Serious Adverse Events (SAEs) | From first dose of study drug up to 30 days following the last dose of study drug (up to 22 months) | |
| Percentage of Participants With AEs Leading to Discontinuation | From first dose of study drug up to 30 days following the last dose of study drug (up to 22 months) | |
| Recommended Phase 2 Dose (RP2D) of TAK-164 | RP2D was the highest safe dose that could be applied to the expansion phase. | Baseline up to Month 22 |
| Secondary Outcome Measures | Measure Description | Time Frame |
|---|---|---|
| Cmax: Maximum Observed Plasma Concentration for TAK-164 | Cycles 1 and 2 Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose (Cycle length = 21 days) | |
| Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for TAK-164 | Cycles 1 and 2 Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose (Cycle length = 21 days) | |
| AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration for TAK-164 | Cycles 1 and 2 Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose (Cycle length = 21 days) | |
| Ctrough: Observed Concentration Measured at the End of a Dosing Interval for TAK-164 | Cycles 1 and 2 Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose (Cycle length = 21 days) | |
| Overall Response Rate (ORR) | ORR was assessed by the investigator based on modified Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. ORR was defined as the percentage of participants who had complete response (CR) or partial response (PR). CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to <10 millimeters (mm). PR was defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum longest diameter. | From start of study treatment until the start of subsequent anti cancer therapy ( up to Month 22) |
| Disease Control Rate (DCR) | DCR was defined as the percentage of participants with CR, PR or stable disease (SD). DCR was assessed based on modified RECIST version 1.1 criteria. CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum longest diameter since the treatment started. | Baseline up to Month 22 |
| Duration of Response (DOR) | DOR was defined as the time from the date of first documentation of a response (CR or PR) to the date of first documented PD or death due to any cause, whichever occurred first based on modified RECIST version 1.1 criteria. CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum longest diameters. PD was >=20% increase in sum of diameters of target lesions, reference-smallest sum recorded in study (sum at baseline if that was smallest). Sum of diameters must have absolute increase of >=5 mm. Appearance of >=1 new lesions also considered PD. | From the date of first documentation of a response (CR or PR) to the date of first documented PD or death due to any cause, whichever occurred first (up to 22 months) |
| Progression-free Survival (PFS) | PFS was defined as the time from date of first study drug administration to the day of first documented PD or death due to any cause, whichever occurred first according to modified RECIST version 1.1 criteria. PD was >= 20% increase in sum of diameters of target lesions, reference-smallest sum recorded in study (sum at baseline if that was smallest). Sum of diameters must have absolute increase of >=5 mm. Appearance of >=1 new lesions also considered PD. PFS was censored at the last response assessment that is stable disease or better, prior to receipt of subsequent anticancer therapy, if applicable. Participants with no post-baseline assessments was censored at Day 1. | From date of first study drug administration to the day of first documented PD or death due to any cause, whichever occurred first (up to 22 months) |
| Number of Participants With Positive Antidrug Antibody (ADA) Levels in Serum | Baseline up to Month 22 |
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.
Ages Eligible for Study:
ALL
Sexes Eligible for Study:
18 Years
Accepts Healthy Volunteers:
This is where you will find people and organizations involved with this study.
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
