Clinical Trials /

Tucatinib Plus Trastuzumab in Patients With HER2+ Colorectal Cancer

NCT03043313

Description:

This trial studies how well the drug tucatinib works when given with trastuzumab and when given by itself. The participants in this trial have HER2-postive (HER2+) metastatic colorectal cancer (mCRC). 'Metastatic' means that the cancer has spread to other parts of the body. In the first part of this study, participants enrolled into Cohort A and received both tucatinib and trastuzumab. In the second part of this study, participants are randomly assigned to either Cohort B or Cohort C. Participants in Cohort B will receive tucatinib and trastuzumab. Participants in Cohort C will receive tucatinib. Participants in Cohort C who do not respond to therapy may have an option to receive tucatinib plus trastuzumab.

Related Conditions:
  • Colorectal Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Tucatinib Plus Trastuzumab in Patients With HER2+ Colorectal Cancer
  • Official Title: MOUNTAINEER: A Phase II, Open Label Study of Tucatinib Combined With Trastuzumab in Patients With HER2+ Metastatic Colorectal Cancer

Clinical Trial IDs

  • ORG STUDY ID: SGNTUC-017
  • SECONDARY ID: NCI-2017-01107
  • SECONDARY ID: ACCRU-GI-1617
  • SECONDARY ID: P30CA015083
  • NCT ID: NCT03043313

Conditions

  • Metastatic Colorectal Adenocarcinoma

Interventions

DrugSynonymsArms
TrastuzumabHerceptinCohort A: Tucatinib + Trastuzumab
TucatinibARRY-380, ONT-380Cohort A: Tucatinib + Trastuzumab

Purpose

This trial studies how well the drug tucatinib works when given with trastuzumab and when given by itself. The participants in this trial have HER2-postive (HER2+) metastatic colorectal cancer (mCRC). 'Metastatic' means that the cancer has spread to other parts of the body. In the first part of this study, participants enrolled into Cohort A and received both tucatinib and trastuzumab. In the second part of this study, participants are randomly assigned to either Cohort B or Cohort C. Participants in Cohort B will receive tucatinib and trastuzumab. Participants in Cohort C will receive tucatinib. Participants in Cohort C who do not respond to therapy may have an option to receive tucatinib plus trastuzumab.

Trial Arms

NameTypeDescriptionInterventions
Cohort A: Tucatinib + TrastuzumabExperimentalNon-randomized cohort. Participants take tucatinib twice per day orally on Days 1-21 and trastuzumab intravenously (into the vein; IV) on Day 1. Cycles repeat every 21 days.
  • Trastuzumab
  • Tucatinib
Cohort B: Tucatinib + TrastuzumabExperimentalRandomized cohort. Participants take tucatinib twice per day orally on Days 1-21 and trastuzumab intravenously (into the vein; IV) on Day 1. Cycles repeat every 21 days.
  • Trastuzumab
  • Tucatinib
Cohort C: Tucatinib MonotherapyExperimentalRandomized cohort. Participants take tucatinib twice per orally every day. Participants who do not respond to therapy may have the option to receive tucatinib and trastuzumab.
  • Tucatinib

Eligibility Criteria

        Inclusion Criteria

          -  Histologically and/or cytologically documented adenocarcinoma of the colon or rectum
             that is metastatic and/or unresectable

          -  Unless contraindicated, participants must have received and failed regimens containing
             the following agents: fluoropyrimidine (e.g., 5-fluorouracil or capecitabine),
             oxaliplatin, irinotecan, an anti-VEGF monoclonal antibody (bevacizumab, ramucirumab,
             or ziv-aflibercept), and an anti-PD-(L)1 therapy (nivolumab or pembrolizumab) if tumor
             has deficient mismatch repair proteins or is MSI-High.

          -  Have progression of unresectable or metastatic CRC after the last systemic therapy, or
             be intolerant of last systemic therapy

          -  Have RAS wild-type in primary or metastatic tumor tissue, based on expanded RAS
             testing

          -  Willing and able to provide the most recent tissue blocks obtained prior to treatment
             initiation. If archival tissue is not available, then a newly-obtained baseline biopsy
             of an accessible tumor

          -  Have confirmed HER2-positive mCRC, as defined by having tumor tissue tested at a
             Clinical Laboratory Improvement Act (CLIA)-certified laboratory, meeting at least one
             of the following criteria:

               -  HER2+ overexpression (3+ immunohistochemistry [IHC])by an FDA-approved HER2 ICH
                  test

               -  HER2 2+ IHC is eligible if the tumor is amplified by an FDA-approved HER2 in situ
                  hybridization assay (FISH or chromogenic in situ hybridization [CISH]))

               -  HER2 (ERBB2) amplification by CLIA-certified next generation sequencing (NGS)
                  sequencing assay

          -  Have radiographically measurable disease assessable by RECIST 1.1, with at least one
             site of disease that is measurable and that has not been previously irradiated; or, if
             the participant has had previous radiation to the target lesion(s), there must be
             evidence of progression since the radiation

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2

          -  Life expectancy greater than 3 months

          -  Have adequate hematological, hepatic, renal, coagulation, and cardiac function

        Exclusion Criteria

          -  Previous treatment with anti-HER2 targeting therapy

          -  Previous treatment with any systemic anticancer therapy, non-central nervous system
             radiation, or experimental agent within 3 weeks of first dose of study treatment

          -  Toxicity related to prior cancer therapies that has not resolved to ≤ Grade 1, with
             the following exceptions:

               -  Alopecia and neuropathy, which must have resolved to ≤ Grade 2

               -  Congestive heart failure (CHF), which must have been ≤ Grade 1 in severity at the
                  time of occurrence, and must have resolved completely

               -  Anemia, which must have resolved to ≤ Grade 2

               -  Decreased ANC, which must have resolved to ≤ Grade 2

          -  Have clinically significant cardiopulmonary disease

          -  Have known myocardial infarction, unstable angina, cardiac or other vascular stenting,
             angioplasty, or cardiac surgery within 6 months prior to first dose of study treatment

          -  Major surgical procedure, open biopsy, or significant traumatic injury ≤28 days prior
             to enrollment (≤56 days for hepatectomy, open thoracotomy, or major neurosurgery) or
             anticipation of need for major surgical procedure during the study

          -  Serious, non-healing wound, ulcer, or bone fracture

          -  Known to be positive for hepatitis B by surface antigen expression

          -  Known to have active hepatitis C infection

             o Exception for participants with a documented sustained virologic response of 12
             weeks

          -  Known to be positive for human immunodeficiency virus (HIV)

          -  Subjects who are pregnant, breastfeeding, or planning a pregnancy

          -  Inability to swallow pills or any significant gastrointestinal disease which would
             preclude the adequate oral absorption of medications

          -  Have used strong CYP2C8 inhibitor within 5 half-lives of the inhibitor, or have used a
             CYP2C8 inducer within 5 days prior to first dose of study treatment

          -  History of another malignancy within 3 years before the first dose of study drug, or
             any evidence of residual disease from a previously diagnosed malignancy.

             o Exceptions are malignancies with a negligible risk of metastasis or death

          -  Subjects with known active CNS metastasis o Irradiated or resected lesions are
             permitted, provided the lesions are fully treated and inactive, subject is
             asymptomatic, and no steroids have been administered for at least 30 days
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Confirmed objective response rate (cORR) per RECIST 1.1 per blinded independent central review (BICR) in pooled Cohorts A+B
Time Frame:Up to 8 months
Safety Issue:
Description:cORR is defined as confirmed complete response (CR) or partial response (PR).

Secondary Outcome Measures

Measure:ORR at 12 weeks of treatment per RECIST 1.1 according to BICR assessment
Time Frame:Up to 12 weeks
Safety Issue:
Description:
Measure:Duration of response (DOR) per RECIST 1.1 according to BICR assessment
Time Frame:Up to approximately 4 years
Safety Issue:
Description:
Measure:Progression-free survival (PFS) per RECIST 1.1 according to BICR assessment for pooled Cohorts A+B
Time Frame:Up to approximately 4 years
Safety Issue:
Description:PFS is defined as the time from start of study treatment (Cohort A) or randomization (Cohort B) to first documentation of tumor progression or to death due to any cause.
Measure:Overall survival (OS) in pooled Cohorts A+B
Time Frame:Up to approximately 4 years
Safety Issue:
Description:OS is defined as the time from start of study treatment (Cohort A) or randomization (Cohort B) to date of death due to any cause.
Measure:Incidence of adverse events (AEs)
Time Frame:Through 30 days following last dose; up to approximately 9 months overall per subject
Safety Issue:
Description:
Measure:Incidence of dose modifications
Time Frame:Through 30 days following last dose; up to approximately 9 months overall per subject
Safety Issue:
Description:
Measure:Incidence of laboratory abnormalities
Time Frame:Through 30 days following last dose; up to approximately 9 months overall per subject
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Seattle Genetics, Inc.

Trial Keywords

  • HER2
  • ERBB2
  • Colorectal cancer

Last Updated

December 1, 2019