Tucatinib Plus Trastuzumab in Patients With HER2+ Colorectal Cancer

Metastatic Colorectal Adenocarcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03043313
• Other study ID #: SGNTUC-017
• Secondary ID: NCI-2017-01107AC
• Status: Completed
• Phase: Phase 2
• Start date: June 23, 2017
• Est. completion date: November 2, 2023

Study information

• Verified date: November 2023
• Source: Seagen Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 117
• Est. completion date: November 2, 2023
• Est. primary completion date: March 28, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Adenocarcinoma

Intervention

Drug:
• Trastuzumab
Given intravenously (into the vein; IV)
• Tucatinib
Given orally

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires Saint Luc	Brussels	Other
Belgium	Universitair Ziekenhuis Antwerpen	Edegem	Other
Belgium	UZ Leuven campus Gasthuisberg	Leuven	Other
France	Hospitalier Jean Minjoz	Besancon	Other
France	Center Georges Francois Leclerc	Dijon	Other
France	Hôpital Franco-Britannique - Fondation Cognacq-Jay	Levallois-Perret	Other
France	Centre Leon Berard - Centre regional de lutte contre le cancer Rhone-Alpes	Lyon	Other
France	Hopital Saint-Antoine	Paris	Other
Italy	Instituto Europeo di Oncologia	Milan	Other
Italy	Niguarda Ca' Granda Hospital	Milan	Other
Italy	Azienda Ospedaliero-Universitaria Pisana - Ospedale S. Chiara	Pisa	Other
Spain	Hospital Universitario Vall d'Hebron	Barcelona	Other
Spain	Institut Catala d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)	L'Hospitalet de Llobregat	Other
Spain	Hospital General Universitario Gregorio Maranon	Madrid	Other
Spain	Hospital Clinico Universitario de Valencia	Valencia	Other
United States	Winship Cancer Institute / Emory University School of Medicine	Atlanta	Georgia
United States	Rocky Mountain Cancer Centers - Aurora	Aurora	Colorado
United States	Texas Oncology - Beaumont	Beaumont	Texas
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	University of Chicago Medical Center	Chicago	Illinois
United States	Case Western Reserve University / University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Texas Oncology - Baylor Sammons Cancer Center	Dallas	Texas
United States	Karmanos Cancer Institute / Wayne State University	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	Providence Regional Medical Center Everett	Everett	Washington
United States	Florida Cancer Specialists - South Region	Fort Myers	Florida
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	Indiana University Simon Cancer Center	Indianapolis	Indiana
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Pacific Shores Medical Group	Long Beach	California
United States	Cedars Sinai Medical Center / Samuel Oschin Comprehensive Cancer Institute	Los Angeles	California
United States	Keck Medical Center / University of Southern California	Los Angeles	California
United States	Joe Arrington Cancer Research and Treatment Center	Lubbock	Texas
United States	Texas Oncology - McAllen	McAllen	Texas
United States	Aurora Research Institute Cancer Center	Milwaukee	Wisconsin
United States	Tennessee Oncology-Nashville/Sarah Cannon Research Institute	Nashville	Tennessee
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Stanford University School of Medicine	Palo Alto	California
United States	Mayo Clinic Arizona	Phoenix	Arizona
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	Northwest Cancer Specialists, P.C.	Portland	Oregon
United States	Oregon Health and Science University	Portland	Oregon
United States	Mayo Clinic Rochester	Rochester	Minnesota
United States	Florida Cancer Specialists - North Region	Saint Petersburg	Florida
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	Texas Oncology - San Antonio Medical Center	San Antonio	Texas
United States	Saint Joseph Heritage Medical Group	Santa Rosa	California
United States	Seattle Cancer Care Alliance / University of Washington	Seattle	Washington
United States	Texas Oncology - Tyler	Tyler	Texas
United States	Lombardi Cancer Center / Georgetown University Medical Center	Washington	District of Columbia
United States	University of Kansas Cancer Center	Westwood	Kansas

Sponsors (3)

Lead Sponsor	Collaborator
Seagen Inc.	Academic and Community Cancer Research United, National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Belgium,  France,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Confirmed Objective Response Rate (cORR) Per RECIST 1.1 Per Blinded Independent Central Review (BICR) in Pooled Cohorts A+B	cORR is defined as the percentage of participants with confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).	Up to 46.6 months
Secondary	ORR by 12 Weeks of Treatment Per RECIST 1.1 According to BICR Assessment	ORR per BICR by 12 Weeks is defined as the percentage of participants with CR or PR by 12 weeks of treatment, and before time of crossover (Cohort C), whichever comes earlier.	Up to 3 months
Secondary	Duration of Response (DOR) Per RECIST 1.1 According to BICR Assessment	DOR is defined as the time from the first objective response (CR or PR that is subsequently confirmed) to documented PD per RECIST 1.1 or death from any cause, whichever occurs first.	Up to 44.7 months
Secondary	Progression-Free Survival (PFS) Per RECIST 1.1 According to BICR Assessment for Pooled Cohorts A+B	PFS is defined as the time from start of study treatment (Cohort A) or date of randomization (Cohort B) to documented disease progression (as determined by BICR per RECIST 1.1) or death from any cause, whichever occurs first.	Up to 46.6 months
Secondary	Overall Survival (OS) in Pooled Cohorts A+B	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.	Up to 53 months
Secondary	Number of Participants With Adverse Events (AEs)	An AE is any untoward medical occurrence in a patient or clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Treatment emergent AEs (TEAEs) are defined as events that are new or worsened on or after receiving the first dose of study treatment (tucatinib or trastuzumab) and up through 30 days after the last dose of study treatment (tucatinib or trastuzumab).	Up to 49.3 months
Secondary	Number of Participants With AEs Resulting in Dose Modification	Dose modification included dose reduction and dose withheld by investigator due to AEs. Dose holds were defined as any instances where planned administration of the study drug was temporarily withheld or interrupted at the direction of the treating physician. Dose reductions of trastuzumab were not allowed; if trastuzumab could not be restarted after being held for a TEAE, it was discontinued.	Up to 49.3 months
Secondary	Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology)	Treatment emergent laboratory abnormalities are defined as abnormalities that are new or worsened on or after receiving the first dose of study treatment and up through 30 days after the last dose of study treatment. NCI CTCAE v5.0 is used for creatinine increased. NCI CTCAE v4.03 is used for the other lab parameters.	Up to 49.3 months
Secondary	Number of Participants With Treatment-Emergent Laboratory Abnormalities (Chemistry)	Treatment emergent laboratory abnormalities are defined as abnormalities that are new or worsened on or after receiving the first dose of study treatment and up through 30 days after the last dose of study treatment. NCI CTCAE v5.0 is used for creatinine increased. NCI CTCAE v4.03 is used for the other lab parameters.	Up to 49.3 months