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A Study of TAK-164 in Participants With Advanced Gastrointestinal (GI) Cancer Expressing Guanylyl Cyclase C (GCC)

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ClinicalTrials.gov Identifier: NCT03449030
Recruitment Status : Recruiting
First Posted : February 28, 2018
Last Update Posted : August 26, 2019
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

Brief Summary:
The purpose of this study is to evaluate the safety of TAK-164 and to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) and schedule.

Condition or disease Intervention/treatment Phase
Gastrointestinal Neoplasms; Esophageal, Stomach, Pancreas, Colon Neoplasms; Malignant Tumors of Digestive Organ; Advanced Gastrointestinal Malignancies Drug: TAK-164 Drug: 89Zr-TAK-164 Phase 1

Detailed Description:

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 in 2 arms planned dose escalation scheme. 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.

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 disease progression (PD), unacceptable toxicity, or until they choose to withdraw consent.

In Part C (Imaging substudy), approximately 25 participants 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 to include United States and 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: An Open-Label, Dose Escalation, Phase 1, First-in-Human Study of TAK-164, an Antibody-Drug Conjugate, in Patients With Advanced Gastrointestinal Cancers Expressing Guanylyl Cyclase C
Actual Study Start Date : April 23, 2018
Estimated Primary Completion Date : April 29, 2021
Estimated Study Completion Date : April 29, 2021

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 disease progression, unacceptable toxicity or discontinuation by participant. Dose escalation will be performed to determine the MTD and RP2D.
Drug: TAK-164
TAK-164 intravenous infusion.

Experimental: Part B Expansion Stage: TAK-164
TAK-164 dose and dosage regimen to be decided based on safety data and MTD/RP2D obtained from Part A escalation stage.
Drug: TAK-164
TAK-164 intravenous infusion.

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 disease progression, unacceptable toxicity or discontinuation by participant. TAK-164 dose to be decided based on safety data and MTD/RP2D obtained from Part A escalation stage.
Drug: TAK-164
TAK-164 intravenous infusion.

Drug: 89Zr-TAK-164
89Zr-TAK-164 intravenous infusion




Primary Outcome Measures :
  1. Number of Participants with Dose-limiting Toxicities (DLTs) [ Time Frame: Up to 36 months ]
    DLTs will be evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.

  2. Percentage of Participants with Adverse Events (AEs) [ Time Frame: Up to 36 months ]
  3. Percentage of Participants with Grade 3 or Above AEs [ Time Frame: Up to 36 months ]
    AE Grades will be evaluated as per NCI CTCAE, version 5.

  4. Percentage of Participants with Drug-related AEs [ Time Frame: Up to 36 months ]
  5. Percentage of Participants with Drug-related Grade 3 or Above AEs [ Time Frame: Up to 36 months ]
    AE Grades will be evaluated as per NCI CTCAE, version 5.

  6. Percentage of Participants with Serious Adverse Events (SAEs) [ Time Frame: Up to 36 months ]
  7. Percentage of Participants with AEs Leading to Discontinuation [ Time Frame: Up to 36 months ]
  8. Percentage of Participants who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests Once Post Dose [ Time Frame: Up to 36 months ]
  9. Percentage of Participants who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose [ Time Frame: Up to 36 months ]
  10. MTD or an Alternate RP2D of TAK-164 [ Time Frame: Up to 36 months ]

Secondary Outcome Measures :
  1. Cmax: Maximum Observed Plasma Concentration for TAK-164 [ Time Frame: Cycle 1 and 2 Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose [Cycle length is equal to (=) 21 days] ]
  2. Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for TAK-164 [ Time Frame: Cycle 1 and 2 Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose (Cycle length = 21 days) ]
  3. AUClast: Area Under the Plasma Concentration-time Curve from Time 0 to Time of Last Quantifiable Concentration for TAK-164 [ Time Frame: Cycle 1 and 2 Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose (Cycle length = 21 days) ]
  4. Ctrough: Observed Concentration Measured at the end of a Dosing Interval for TAK-164 [ Time Frame: Cycle 1 and 2 Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose (Cycle length = 21 days) ]
  5. Overall Response Rate (ORR) [ Time Frame: Up to 36 months ]
    ORR is defined as the percentage of participants with complete response (CR), or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

  6. Disease Control Rate (DCR) [ Time Frame: Up to 36 months ]
    DCR is defined as the percentage of participants with CR, PR or stable disease (SD) with a minimum of 12 weeks duration. DCR will be assessed based on RECIST version 1.1 criteria.

  7. Duration of Response (DOR) [ Time Frame: Up to 36 months ]
    DOR is defined as the time from the date of first documentation of a response to the date of first documentation of PD according to RECIST version 1.1 criteria.

  8. Progression-free Survival (PFS) [ Time Frame: Up to 36 months ]
    PFS is defined as the time from the date of first study drug administration to the date of first documentation of PD or death. PFS will be assessed based on RECIST version 1.1 criteria.

  9. Number of Participants with Antidrug Antibody (ADA) Levels in Serum [ Time Frame: Up to 36 months ]
  10. Part C: Mean Standardized Patient-level Biodistribution Value of Zicronium 89-labeled-TAK-164 (89Zr-TAK-164) [ Time Frame: Day -14: at 1 hour post 89Zr-TAK-164 end of infusion (EOI), Days -12 and -10, and Days 3 and 5 (Cycle 1): post 89Zr-TAK-164 EOI (Cycle length = 21 days) ]
  11. Part C: Relationship Between 89Zr-TAK-164 and Zr-TAK-164 Positron Emission Tomography (PET) Scan [ Time Frame: Day -14: at 1 hour post 89Zr-TAK-164 EOI, Days -12 and -10, and Days 3 and 5 (Cycle 1): post 89Zr-TAK-164 EOI (Cycle length = 21 days) ]
  12. Part C: Mean Standardized Uptake Value (SUV) of 89Zr-TAK-164 Uptake in Tumor Lesions [ Time Frame: Days -12 and -10, and Days 3 and 5 (Cycle 1): post 89Zr-TAK-164 EOI (Cycle length = 21 days) ]
  13. Part C: Relationship between 89Zr-TAK-164 uptake in Tumor Lesions and Computed Tomography (CT) or 18-flurodeoxyglycose (18F-FDG) positron emission tomography (PET) [ Time Frame: Days -12 and -10, and Days 3 and 5 (Cycle 1): post 89Zr-TAK-164 EOI (Cycle length = 21 days) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically or cytologically confirmed measurable advanced and/or metastatic solid GI tumor that expresses GCC protein, for which standard treatment is no longer effective or does not offer curative or life-prolonging benefit. For the escalation part of the study (Part A), GI malignancies include, but are not limited to, metastatic colorectal carcinoma (mCRC), gastric carcinoma, esophageal carcinoma, small intestine cancer, and pancreatic cancer. The expansion part of the study (Part B) is limited to participants with CRC and gastric carcinoma. Part C includes participants with CRC and gastric carcinoma.
  2. Male or female participants 18 years or older.
  3. Adequate bone marrow function, defined as an absolute neutrophil count (ANC) of >=1.5*109 per liter (/L), platelet count >=100*109/L, and hemoglobin >=9 gram per deciliter (g/dL). Receiving transfusions or hematopoietic growth factors to meet enrollment criteria is not allowed within 14 days preceding the first dose of study drug.
  4. Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1.
  5. Life expectancy of at least 12 weeks.
  6. Completion of prior chemotherapy, biologic therapy, immunotherapy, or radiation therapy at least 4 weeks prior to enrollment.
  7. Resolution of all toxic effects of prior treatments (except alopecia) to Grade <=1 NCI CTCAE, Version 5.
  8. A portion of participants should have tumors amenable for serial biopsy and a willingness to provide consent for pharmacodynamic assessment.

    Additionally for Part C (imaging sub study), participant must fulfill the following criteria:

  9. At least 1 extrahepatic metastatic lesion >=2 centimeter (cm) in the longest diameter.

Exclusion Criteria:

  1. Treatment with anticancer chemotherapy or biologic therapy or with an experimental anticancer agent within 28 days of the initial dose of study drug.
  2. Diagnosed or treated for another malignancy within 2 years before administration of the first dose of study drug, or previously diagnosed with another malignancy and have any evidence of residual disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
  3. Participant has a history of severe allergic or anaphylactic reactions to recombinant proteins or excipients used in TAK-164 formulation.
  4. Use of strong cytochrome P3A (CYP3A) inhibitors and CYP3A inducers or inhibitors or modulators of P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP) within 1 week before the first dose of study drug.
  5. For participants enrolled in studies in which tumor biopsies are obtained:

    • Known bleeding diathesis or history of abnormal bleeding, or any other known coagulation abnormalities that would contraindicate the tumor biopsy procedure.
    • Ongoing therapy with any anticoagulant or antiplatelet agents (example, aspirin, clopidogrel, heparin, or warfarin).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03449030


Contacts
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Contact: Takeda Study Registration Call Center +1-844-662-8532 globaloncologymedinfo@takeda.com

Locations
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United States, Colorado
University of Colorado Cancer Center Not yet recruiting
Aurora, Colorado, United States, 80045
United States, Florida
Moffitt Cancer Center Not yet recruiting
Tampa, Florida, United States, 33612
United States, Massachusetts
Massachusetts General Hospital Not yet recruiting
Boston, Massachusetts, United States, 02114-2621
United States, Tennessee
SCRI - Tennessee Oncology Nashville - Southern Hills Clinic Recruiting
Nashville, Tennessee, United States, 37205
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Investigators
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Study Director: Medical Director Millennium Pharmaceuticals, Inc.

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Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT03449030     History of Changes
Other Study ID Numbers: TAK-164-1001
U1111-1207-9923 ( Other Identifier: WHO )
2018-002214-12 ( Registry Identifier: EudraCT )
First Posted: February 28, 2018    Key Record Dates
Last Update Posted: August 26, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available after applicable marketing approvals and commercial availability have been received, an opportunity for the primary publication of the research has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com/Approach for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Takeda ( Millennium Pharmaceuticals, Inc. ):
Drug Therapy
Additional relevant MeSH terms:
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Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Neoplasms
Colonic Neoplasms
Neoplasms
Neoplasms by Site
Gastrointestinal Diseases
Colorectal Neoplasms
Intestinal Neoplasms
Colonic Diseases
Intestinal Diseases