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Tucatinib Plus Trastuzumab and Oxaliplatin-based Chemotherapy for HER2+ Gastrointestinal Cancers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04430738
Recruitment Status : Recruiting
First Posted : June 12, 2020
Last Update Posted : November 10, 2020
Information provided by (Responsible Party):
Seagen Inc.

Brief Summary:

This trial studies tucatinib to find out if it is safe when given with trastuzumab and other anti-cancer drugs (FOLFOX). It will look at what side effects happen when participants take this combination of drugs. A side effect is anything the drug does other than treating cancer.

The participants in this trial have HER2-positive (HER2+) cancer in their gut, stomach, intestines, or gallbladder (gastrointestinal cancer).

Condition or disease Intervention/treatment Phase
Colorectal Carcinoma Gastric Adenocarcinoma Esophageal and GEJ Adenocarcinoma Cholangiocarcinoma Gallbladder Carcinoma Drug: tucatinib Drug: trastuzumab Drug: oxaliplatin Drug: leucovorin Drug: fluorouracil Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b Dose Escalation Study of Tucatinib in Combination With Trastuzumab and Oxaliplatin-based Chemotherapy for HER2+ Gastrointestinal Cancers
Actual Study Start Date : September 15, 2020
Estimated Primary Completion Date : May 25, 2021
Estimated Study Completion Date : July 9, 2021

Arm Intervention/treatment
Experimental: Single Arm
Tucatinib + trastuzumab + oxaliplatin + leucovorin + fluorouracil
Drug: tucatinib
150 mg will be administered twice daily orally for Cycle 1 Day 8 onwards. Dose escalation levels may also be evaluated.
Other Name: TUKYSA

Drug: trastuzumab
6 mg/kg will be administered intravenously (into the vein; IV) on Cycle 1 Day 1 and then will be administered at 4 mg/kg every 2 weeks starting on Cycle 2 Day 1.

Drug: oxaliplatin
85 mg/m2 administered IV every 2 weeks starting from Cycle 1 Day 1 onwards

Drug: leucovorin
200 mg/m2 administered IV every 2 weeks starting from Cycle 1 Day 1 onwards

Drug: fluorouracil
2400 mg/m2 administered IV every 2 weeks starting from Cycle 1 Day 1 onwards

Primary Outcome Measures :
  1. Incidence of renal dose-limiting toxicities (DLTs) [ Time Frame: Up to one month; 2 cycles after receiving all study treatment (each cycle is 14 days) ]

Secondary Outcome Measures :
  1. Incidence of adverse events [ Time Frame: Up to approximately 12 months ]
  2. Change in glomerular filtration rate from baseline through 2 cycles of combination therapy [ Time Frame: Up to approximately 12 months ]
  3. Pharmocokinetic (PK) parameter of tucatinib - AUClast [ Time Frame: Up to approximately 2.5 months; through predose of Cycle 6, Day 1 (each cycle is 14 days) ]
  4. PK parameter of tucatinib - Cmax [ Time Frame: Up to approximately 2.5 months; through predose of Cycle 6, Day 1 (each cycle is 14 days) ]
  5. PK parameter of tucatinib - Ctrough [ Time Frame: Up to approximately 2.5 months; through predose of Cycle 6, Day 1 (each cycle is 14 days) ]
  6. PK parameter of tucatinib - Tmax [ Time Frame: Up to approximately 2.5 months; through predose of Cycle 6, Day 1 (each cycle is 14 days) ]
  7. PK parameter of oxaliplatin - AUClast [ Time Frame: Up to 16 days; through Cycle 2, Day 2 (each cycle is 14 days) ]
  8. PK parameter of oxaliplatin - Cmax [ Time Frame: Up to 16 days; through Cycle 2, Day 2 (each cycle is 14 days) ]
  9. PK parameter of oxaliplatin - Tmax [ Time Frame: Up to 16 days; through Cycle 2, Day 2 (each cycle is 14 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

Inclusion Criteria:

  • Participants must have unresectable or metastatic solid malignancy that is histologically or cytologically confirmed to be one of the tumor types listed below:

    • CRC
    • Gastric adenocarcinoma
    • Esophageal and GEJ adenocarcinoma
    • Cholangiocarcinoma
    • Gallbladder carcinoma
  • Participants must be receiving or must be candidates to receive an oxaliplatin-based regimen as part of their standard-of-care treatment.

    • If participant is receiving oxaliplatin at the time of enrollment, the oxaliplatin dose in their current regimen must be 85 mg/m2 per 2-week cycle
  • HER2+ disease, as determined by laboratory testing based on one of the following:

    • For colorectal, cholangiocarcinoma, and gallbladder carcinoma:

      • HER2 amplification or overexpression from fresh or archival tumor tissue utilizing one of the following Clinical Laboratory Improvement Amendments (CLIA) certified tests:

        • HER2 overexpression (3+ immunohistochemistry [IHC])
        • HER2 (ERBB2) amplification by in situ hybridization assay (fluorescence in situ hybridization [FISH] or chromogenic in situ hybridization signal ratio ≥2.0 or gene copy number >6)
        • HER2 (ERBB2) amplification by next generation sequencing (NGS) assay
      • HER2 amplification in a CLIA certified blood-based NGS assay
    • Gastric, GEJ, and esophageal adenocarcinomas must use the following criteria:

      • HER2+ overexpression (IHC3+) by an FDA approved assay, from a newly obtained biopsy or surgical specimen, evaluated following the package insert's interpretational manual for gastric adenocarcinoma. IHC2+ is eligible if the tumor is HER2 amplified by an FDA approved in situ hybridization assay
  • Eastern Cooperative Oncology Group Performance Status score of 0 or 1.

Exclusion Criteria:

  • History of allergic reactions to oxaliplatin, fluorouracil, leucovorin, trastuzumab, or compounds chemically or biologically similar to tucatinib, except for Grade 1 or 2 infusion related reactions to oxaliplatin or trastuzumab that were successfully managed, or known allergy to any of the excipients in the study drugs
  • Current treatment regimen with an oxaliplatin dose >85 mg/m2 per 2-week cycle or with an oxaliplatin dose 85 mg/m2 per 2-week cycle that was initiated more than 28 days prior to enrollment

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 identifier (NCT number): NCT04430738

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Contact: Seagen Trial Information Support 8663337436

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United States, Arizona
Mayo Clinic Arizona Recruiting
Phoenix, Arizona, United States, 85054
Contact: Mayo Clinic Clinical Trials Referral Office Inbox    855-776-0015      
Principal Investigator: Tanios Bekaii-Saab         
United States, Colorado
University of Colorado Hospital / University of Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: Matthew Lee    720-848-0300   
Principal Investigator: Sunnie Kim         
United States, Missouri
Washington University in St Louis Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Viktoriia Hicks    314-362-3515   
Contact: Jesse Huffman    314-362-3515   
Principal Investigator: Haeseong Park, MD         
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Ireka Burrus    919-668-1861   
Principal Investigator: John Strickler, MD         
United States, Ohio
The Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
Contact: Suneel Kamath    216-445-9451   
Principal Investigator: Suneel Kamath         
Sponsors and Collaborators
Seagen Inc.
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Study Director: Michael Stecher, MD Seagen Inc.
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Responsible Party: Seagen Inc. Identifier: NCT04430738    
Other Study ID Numbers: SGNTUC-024
First Posted: June 12, 2020    Key Record Dates
Last Update Posted: November 10, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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 Seagen Inc.:
Seattle Genetics
Additional relevant MeSH terms:
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Colorectal Neoplasms
Gastrointestinal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Intestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Immunological
Protective Agents