Clinical trial NCT03043313: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Colorectal Adenocarcinoma
Keywords: HER2
ERBB2
Colorectal cancer
Seattle Genetics
Lead sponsor: Seagen Inc.
Sponsor class: INDUSTRY
Collaborators: name: National Cancer Institute (NCI)
name: Academic and Community Cancer Research United
First posted: 2017-02-06
Enrollment: 117
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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-positive (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.


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 recently available 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 or International Organization for Standardization (ISO)-accredited laboratory, meeting at least one of the following criteria:

  * HER2+ overexpression (3+ immunohistochemistry \[IHC\]) by an FDA-approved or Conformité Européene (CE)-marked HER2 ICH test
  * HER2 2+ IHC is eligible if the tumor is amplified by an FDA-approved or CE-marked HER2 in situ hybridization assay (FISH or chromogenic in situ hybridization \[CISH\]))
  * HER2 (ERBB2) amplification by CLIA-certified or ISO-accredited 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

  * 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 strong CYP2C8 or CYP3A4 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.

  * Exceptions are malignancies with a negligible risk of metastasis or death
* Subjects with known active CNS metastasis

  * 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

Primary outcomes:
measure: Confirmed Objective Response Rate (cORR) Per RECIST v1.1 Per Blinded Independent Central Review (BICR) in Pooled Cohorts A+B
timeFrame: Up to 46.6 months
Secondary outcomes:
measure: ORR by 12 Weeks of Treatment Per RECIST v1.1 According to BICR Assessment
timeFrame: Up to 3 months
measure: Duration of Response (DOR) Per RECIST v1.1 According to BICR Assessment
timeFrame: Up to 64.1 months
measure: Progression-Free Survival (PFS) Per RECIST v1.1 According to BICR Assessment for Pooled Cohorts A+B
timeFrame: Up to 64.1 months
measure: Overall Survival (OS) in Pooled Cohorts A+B
timeFrame: Up to 71.8 months
measure: Number of Participants With Adverse Events (AEs): Interim Analysis
timeFrame: Up to 49.3 months
measure: Number of Participants With AEs: Final Analysis
timeFrame: Up to 65.1 months
measure: Number of Participants With AEs Resulting in Dose Modification: Interim Analysis
timeFrame: Up to 49.3 months
measure: Number of Participants With AEs Resulting in Dose Modification: Final Analysis
timeFrame: Up to 65.1 months
measure: Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology): Interim Analysis
timeFrame: Up to 49.3 months
measure: Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology): Final Analysis
timeFrame: Up to 65.1 months
measure: Number of Participants With Treatment-Emergent Laboratory Abnormalities (Chemistry): Interim Analysis
timeFrame: Up to 49.3 months
measure: Number of Participants With Treatment-Emergent Laboratory Abnormalities (Chemistry): Final Analysis
timeFrame: Up to 65.1 months
measure: Number of Participants With Clinically Significant Vital Signs: Final Analysis
timeFrame: Up to 65.1 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Phoenix
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Long Beach
country: United States
facility: Pacific Shores Medical Group
state: California
city: Los Angeles
country: United States
facility: Keck Medical Center / University of Southern California
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center / Samuel Oschin Comprehensive Cancer Institute
state: California
city: Palo Alto
country: United States
facility: Stanford University School of Medicine
state: California
city: Santa Rosa
country: United States
facility: Saint Joseph Heritage Medical Group
state: California
city: Aurora
country: United States
facility: Rocky Mountain Cancer Centers - Aurora
state: Colorado
city: Washington
country: United States
facility: Lombardi Cancer Center / Georgetown University Medical Center
state: District of Columbia
city: Fort Myers
country: United States
facility: Florida Cancer Specialists - South Region
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists - North Region
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute / Emory University School of Medicine
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Simon Cancer Center
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Westwood
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute / Wayne State University
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Case Western Reserve University / University Hospitals Cleveland Medical Center
state: Ohio
city: Portland
country: United States
facility: Northwest Cancer Specialists, P.C.
state: Oregon
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Nashville
country: United States
facility: Tennessee Oncology-Nashville/Sarah Cannon Research Institute
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Beaumont
country: United States
facility: Texas Oncology - Beaumont
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Baylor Sammons Cancer Center
state: Texas
city: Lubbock
country: United States
facility: Joe Arrington Cancer Research and Treatment Center
state: Texas
city: McAllen
country: United States
facility: Texas Oncology - McAllen
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology - San Antonio Medical Center
state: Texas
city: Tyler
country: United States
facility: Texas Oncology - Tyler
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute/University of Utah
state: Utah
city: Everett
country: United States
facility: Providence Regional Medical Center Everett
state: Washington
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance / University of Washington
state: Washington
city: Milwaukee
country: United States
facility: Aurora Research Institute Cancer Center
state: Wisconsin
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint Luc
state: Other
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
state: Other
city: Leuven
country: Belgium
facility: UZ Leuven campus Gasthuisberg
state: Other
city: Besancon
country: France
facility: Hospitalier Jean Minjoz
state: Other
city: Dijon
country: France
facility: Center Georges Francois Leclerc
state: Other
city: Levallois-Perret
country: France
facility: Hôpital Franco-Britannique - Fondation Cognacq-Jay
state: Other
city: Lyon
country: France
facility: Centre Leon Berard - Centre regional de lutte contre le cancer Rhone-Alpes
state: Other
city: Paris
country: France
facility: Hopital Saint-Antoine
state: Other
city: Milan
country: Italy
facility: Instituto Europeo di Oncologia
state: Other
city: Milan
country: Italy
facility: Niguarda Ca' Granda Hospital
state: Other
city: Pisa
country: Italy
facility: Azienda Ospedaliero-Universitaria Pisana - Ospedale S. Chiara
state: Other
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
state: Other
city: L'Hospitalet de Llobregat
country: Spain
facility: Institut Catala d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)
state: Other
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
state: Other
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
state: Other
Study officials:
affiliation: Academic and Community Cancer Research United
name: John H Strickler
role: STUDY_CHAIR
affiliation: Seagen Inc.
name: Jorge Ramos, DO
role: STUDY_DIRECTOR
References: