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

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ClinicalTrials.gov Identifier: NCT04430738
Recruitment Status : Recruiting
First Posted : June 12, 2020
Last Update Posted : July 13, 2021
Sponsor:
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 and CAPOX). 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. It will also look at whether tucatinib works with these drugs to treat certain types of 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 GEJ Adenocarcinoma Esophageal Adenocarcinoma Cholangiocarcinoma Gallbladder Carcinoma Drug: tucatinib Drug: trastuzumab Drug: oxaliplatin Drug: leucovorin Drug: fluorouracil Drug: capecitabine Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 65 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b/2 Dose Escalation and Expansion 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 : July 31, 2021
Estimated Study Completion Date : November 30, 2022


Arm Intervention/treatment
Experimental: Cohort 1A
Tucatinib + trastuzumab + FOLFOX given in 14-day cycles
Drug: tucatinib
For Cohort 1A, 150 mg will be administered twice daily orally from Cycle 1 Day 8 onwards. For all other cohorts, 300 mg (or intermediate dose) will be given orally twice daily starting on Cycle 1 Day 1.
Other Name: TUKYSA

Drug: trastuzumab
Cohorts 1A, 1B, 2A, and 2B (FOLFOX): a 6 mg/kg loading dose will be given intravenously (into the vein; IV) on Cycle 1 Day 1, followed by a dose of 4 mg/kg IV every 2 weeks starting on Cycle 2 Day 1. Cohorts 1C and 2A (CAPOX): an 8 mg/kg loading dose will be administered IV on Cycle 1 Day 1, followed by a dose of 6 mg/kg IV every 3 weeks starting on Cycle 2 Day 1.

Drug: oxaliplatin
85 mg/m^2 given IV every 2 weeks for cohorts using FOLFOX. For cohorts using CAPOX regimen, 130 mg/m^2 given every 3 weeks.

Drug: leucovorin
200 (mFOLFOX7) or 400 (mFOLFOX6) mg/m^2 given IV every 2 weeks. Part of FOLFOX regimen.

Drug: fluorouracil
400 mg/m^2 (IV bolus after leucovorin) and/or 2400 mg/m^2 (continuous infusion over 46 hours). Part of FOLFOX regimen.

Experimental: Cohort 1B
Tucatinib + trastuzumab + FOLFOX given in 14-day cycles
Drug: tucatinib
For Cohort 1A, 150 mg will be administered twice daily orally from Cycle 1 Day 8 onwards. For all other cohorts, 300 mg (or intermediate dose) will be given orally twice daily starting on Cycle 1 Day 1.
Other Name: TUKYSA

Drug: trastuzumab
Cohorts 1A, 1B, 2A, and 2B (FOLFOX): a 6 mg/kg loading dose will be given intravenously (into the vein; IV) on Cycle 1 Day 1, followed by a dose of 4 mg/kg IV every 2 weeks starting on Cycle 2 Day 1. Cohorts 1C and 2A (CAPOX): an 8 mg/kg loading dose will be administered IV on Cycle 1 Day 1, followed by a dose of 6 mg/kg IV every 3 weeks starting on Cycle 2 Day 1.

Drug: oxaliplatin
85 mg/m^2 given IV every 2 weeks for cohorts using FOLFOX. For cohorts using CAPOX regimen, 130 mg/m^2 given every 3 weeks.

Drug: leucovorin
200 (mFOLFOX7) or 400 (mFOLFOX6) mg/m^2 given IV every 2 weeks. Part of FOLFOX regimen.

Drug: fluorouracil
400 mg/m^2 (IV bolus after leucovorin) and/or 2400 mg/m^2 (continuous infusion over 46 hours). Part of FOLFOX regimen.

Experimental: Cohort 1C
Tucatinib + trastuzumab + CAPOX given in 21-day cycles
Drug: tucatinib
For Cohort 1A, 150 mg will be administered twice daily orally from Cycle 1 Day 8 onwards. For all other cohorts, 300 mg (or intermediate dose) will be given orally twice daily starting on Cycle 1 Day 1.
Other Name: TUKYSA

Drug: trastuzumab
Cohorts 1A, 1B, 2A, and 2B (FOLFOX): a 6 mg/kg loading dose will be given intravenously (into the vein; IV) on Cycle 1 Day 1, followed by a dose of 4 mg/kg IV every 2 weeks starting on Cycle 2 Day 1. Cohorts 1C and 2A (CAPOX): an 8 mg/kg loading dose will be administered IV on Cycle 1 Day 1, followed by a dose of 6 mg/kg IV every 3 weeks starting on Cycle 2 Day 1.

Drug: oxaliplatin
85 mg/m^2 given IV every 2 weeks for cohorts using FOLFOX. For cohorts using CAPOX regimen, 130 mg/m^2 given every 3 weeks.

Drug: capecitabine
1000 mg/m^2 is taken twice per day orally on Days 1-14 of each 3 week cycle. Part of CAPOX regimen.

Experimental: Cohort 2A
Tucatinib + trastuzumab + (FOLFOX or CAPOX)
Drug: tucatinib
For Cohort 1A, 150 mg will be administered twice daily orally from Cycle 1 Day 8 onwards. For all other cohorts, 300 mg (or intermediate dose) will be given orally twice daily starting on Cycle 1 Day 1.
Other Name: TUKYSA

Drug: trastuzumab
Cohorts 1A, 1B, 2A, and 2B (FOLFOX): a 6 mg/kg loading dose will be given intravenously (into the vein; IV) on Cycle 1 Day 1, followed by a dose of 4 mg/kg IV every 2 weeks starting on Cycle 2 Day 1. Cohorts 1C and 2A (CAPOX): an 8 mg/kg loading dose will be administered IV on Cycle 1 Day 1, followed by a dose of 6 mg/kg IV every 3 weeks starting on Cycle 2 Day 1.

Drug: oxaliplatin
85 mg/m^2 given IV every 2 weeks for cohorts using FOLFOX. For cohorts using CAPOX regimen, 130 mg/m^2 given every 3 weeks.

Drug: leucovorin
200 (mFOLFOX7) or 400 (mFOLFOX6) mg/m^2 given IV every 2 weeks. Part of FOLFOX regimen.

Drug: fluorouracil
400 mg/m^2 (IV bolus after leucovorin) and/or 2400 mg/m^2 (continuous infusion over 46 hours). Part of FOLFOX regimen.

Drug: capecitabine
1000 mg/m^2 is taken twice per day orally on Days 1-14 of each 3 week cycle. Part of CAPOX regimen.

Experimental: Cohort 2B
Tucatinib + trastuzumab + FOLFOX
Drug: tucatinib
For Cohort 1A, 150 mg will be administered twice daily orally from Cycle 1 Day 8 onwards. For all other cohorts, 300 mg (or intermediate dose) will be given orally twice daily starting on Cycle 1 Day 1.
Other Name: TUKYSA

Drug: trastuzumab
Cohorts 1A, 1B, 2A, and 2B (FOLFOX): a 6 mg/kg loading dose will be given intravenously (into the vein; IV) on Cycle 1 Day 1, followed by a dose of 4 mg/kg IV every 2 weeks starting on Cycle 2 Day 1. Cohorts 1C and 2A (CAPOX): an 8 mg/kg loading dose will be administered IV on Cycle 1 Day 1, followed by a dose of 6 mg/kg IV every 3 weeks starting on Cycle 2 Day 1.

Drug: oxaliplatin
85 mg/m^2 given IV every 2 weeks for cohorts using FOLFOX. For cohorts using CAPOX regimen, 130 mg/m^2 given every 3 weeks.

Drug: leucovorin
200 (mFOLFOX7) or 400 (mFOLFOX6) mg/m^2 given IV every 2 weeks. Part of FOLFOX regimen.

Drug: fluorouracil
400 mg/m^2 (IV bolus after leucovorin) and/or 2400 mg/m^2 (continuous infusion over 46 hours). Part of FOLFOX regimen.




Primary Outcome Measures :
  1. Incidence of renal dose-limiting toxicities (Cohorts 1A, 1B, and 1C) [ Time Frame: Up to one month; 2 cycles after receiving all study treatment (each cycle is 14 days) ]
  2. Incidence of adverse events (Cohorts 2A and 2B) [ Time Frame: Up to approximately 12 months ]
  3. Incidence of laboratory abnormalities (Cohorts 2A and 2B) [ Time Frame: Up to approximately 12 months ]

Secondary Outcome Measures :
  1. Incidence of adverse events (Cohorts 1A, 1B, and 1C) [ Time Frame: Up to approximately 12 months ]
  2. Change in glomerular filtration rate from baseline through 2 cycles of combination therapy (Cohorts 1A, 1B, and 1C) [ Time Frame: Up to approximately 6 weeks ]
  3. Pharmocokinetic (PK) parameter of tucatinib - AUClast (Cohorts 1A, 1B, and 1C) [ 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 (Cohorts 1A, 1B, and 1C) [ 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 (All cohorts) [ 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 (Cohorts 1A, 1B, and 1C) [ 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 (Cohorts 1A, 1B, and 1C) [ Time Frame: Up to 16 days; through Cycle 2, Day 2 (each cycle is 14 days) ]
  8. PK parameter of oxaliplatin - Cmax (Cohorts 1A, 1B, and 1C) [ Time Frame: Up to 16 days; through Cycle 2, Day 2 (each cycle is 14 days) ]
  9. PK parameter of oxaliplatin - Tmax (Cohorts 1A, 1B, and 1C) [ Time Frame: Up to 16 days; through Cycle 2, Day 2 (each cycle is 14 days) ]
  10. Confirmed objective response rate (cORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 per investigator assessment (INV) (1L gastric, esophogeal, and GEJ Phase 2 cohorts only) [ Time Frame: Up to approximately 2.5 years ]
    cORR is defined as the proportion of participants with confirmed complete response (CR) or partial response (PR)

  11. Duration of response (DOR) according to RECIST v1.1 per INV (Cohort 2A) [ Time Frame: Up to approximately 2.5 years ]
    DOR is defined as the time from first documentation of objective response of confirmed CR or confirmed PR to the first documentation of disease progression or death from any cause, whichever occurs first.

  12. Progression-free survival (PFS) according to RECIST v1.1 per INV (Cohort 2A) [ Time Frame: Up to approximately 2.5 years ]
    PFS is defined as the time from the date of treatment initiation to the date of disease progression or death from any cause, which occurs first.

  13. Overall survival (OS) (Cohort 2A) [ Time Frame: Up to approximately 2.5 years ]
    OS is defined as the time from treatment initiation to death due to any cause



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:

  • 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
    • GEJ adenocarcinoma
    • Esophageal adenocarcinoma
    • Cholangiocarcinoma
    • Gallbladder carcinoma
  • Participants must be candidates to receive an oxaliplatin-based regimen as part of their standard-of-care treatment.
  • Participants in phase 1b cohorts or in Cohort 2B can be receiving an oxaliplatin-based regimen

    • For phase 1b cohorts utilizing FOLFOX: up to 2 cycles of FOLFOX (≤85 mg/m2 oxaliplatin per 2-week cycle) may have been received prior to Cycle 1 Day 1 of study treatment
    • For phase 1b cohorts utilizing CAPOX: up to 2 cycles of FOLFOX (≤85 mg/m2 oxaliplatin per 2-week cycle) or one cycle of CAPOX (≤130 mg/m2 oxaliplatin per 3-week cycle) may have been received prior to Cycle 1 Day 1 of study treatment.
    • For all phase 1b cohorts: if subject has received oxaliplatin in prior cycles at higher doses than those listed above, there must be a minimum of 28 days off treatment prior to Cycle 1 Day 1 of treatment in this study.
    • For Cohort 2B prior to the first dose of study treatment:

      • Subjects may have received up to 1 cycle of FOLFOX (≤85 mg/m2 oxaliplatin per 2-week cycle) prior to Cycle 1 Day 1 but may not have received prior oxaliplatin for metastatic disease
      • Oxaliplatin received in an adjuvant setting is permitted if >6 months prior to Cycle 1 Day 1
      • At least 21 days must have elapsed from prior systemic anticancer therapy (including hormonal and biologic therapy but excluding 1 cycle of FOLFOX), non-central nervous system radiation, and treatment with other experimental agents
  • HER2+ disease, as determined by laboratory testing based on one of the following:

    • For CRC, 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 or International Organization for Standardization (ISO) 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
  • Phase 1b cohorts: measurable or non-measurable disease according to RECIST v1.1 as determined by the investigator
  • Phase 2 cohorts: measurable disease according to RECIST v1.1 as determined by the investigator
  • Eastern Cooperative Oncology Group Performance Status score of 0 or 1.

Exclusion Criteria:

  • History of known hypersensitivity to oxaliplatin, fluoropyrimidines, 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
  • Treatment with oxaliplatin dose in excess of the limitations specified in the inclusion criteria

There are additional inclusion criteria. The study center will determine if criteria for participations are met.


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): NCT04430738


Contacts
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Contact: Seagen Trial Information Support 8663337436 clinicaltrials@seagen.com

Locations
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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, California
Stanford University School of Medicine Recruiting
Stanford, California, United States, 94305
Contact: Smruti Rahalkar    650-498-5186      
Principal Investigator: James M Ford         
Principal Investigator: Christopher T Chen         
United States, Colorado
University of Colorado Hospital / University of Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: Matthew R Lee    720-848-0300    matthew.r.lee@cuanschutz.edu   
Principal Investigator: Sunnie Kim         
United States, District of Columbia
Johns Hopkins Medical Center Recruiting
Washington, District of Columbia, United States, 20016
Contact: Carol Goldener, RN    220-660-6500      
Principal Investigator: Michael Pishvaian         
United States, Missouri
Washington University in St Louis Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Viktoriia Hicks    314-362-3515    viktoriia.hicks@wustl.edu   
Contact: Jesse Huffman    314-362-3515    jessehuffman@wustl.edu   
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    ireka.burrus@duke.edu   
Principal Investigator: John H Strickler, MD         
United States, Ohio
Gabrail Cancer Center Research, LLC Recruiting
Canton, Ohio, United States, 44718
Contact: Carrie Smith    330-492-3345      
Principal Investigator: Nashat Gabrail         
Cleveland Clinic, The Recruiting
Cleveland, Ohio, United States, 44195
Contact: Suneel Kamath    216-445-9451    kamaths@ccf.org   
Principal Investigator: Suneel Kamath         
United States, Washington
Seattle Cancer Care Alliance / University of Washington Recruiting
Seattle, Washington, United States, 98109-1023
Contact: Sean Park    206-606-6439      
Principal Investigator: David B Zhen         
Sponsors and Collaborators
Seagen Inc.
Investigators
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Study Director: Christopher Lux, MD, PhD Seagen Inc.
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Responsible Party: Seagen Inc.
ClinicalTrials.gov Identifier: NCT04430738    
Other Study ID Numbers: SGNTUC-024
First Posted: June 12, 2020    Key Record Dates
Last Update Posted: July 13, 2021
Last Verified: July 2021
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.:
HER2+
HER2-positive
Seattle Genetics
Additional relevant MeSH terms:
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Cholangiocarcinoma
Carcinoma
Adenocarcinoma
Colorectal Neoplasms
Gastrointestinal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Intestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Leucovorin
Fluorouracil
Capecitabine
Oxaliplatin
Trastuzumab
Tucatinib
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Immunological