Tucatinib Combined with Trastuzumab and TAS-102 for the Treatment of HER2 Positive Metastatic Colorectal Cancer in Molecularly Selected Patients, 3T Study

NCT05356897 | Withdrawn Phase 2 DMC FDA Drug

• 3 other identifiers: ACCRU-GI-2003NCI-2022-03147P30CA015083
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

This phase II trial studies whether tucatinib combined with trastuzumab and TAS-102 works to shrink tumors in patients with HER2 positive colorectal cancer that has spread to other parts of the body (metastatic) and has one of the following gene mutations detected in blood: PIK3CA, KRAS, NRAS, or BRAF V600. Tucatinib is in a class of medications called kinase inhibitors. It works by blocking the action of the abnormal protein that signals tumor cells to multiply. This helps stop or slow the spread of tumor cells. Trastuzumab is a form of targeted therapy because it attaches itself to specific molecules (receptors) on the surface of tumor cells, known as HER2 receptors. When trastuzumab attaches to HER2 receptors, the signals that tell the cells to grow are blocked and the tumor cell may be marked for destruction by the body's immune system. TAS-102 is a combination of 2 drugs; trifluridine and tipiracil. Trifluridine is in a class of medications called thymidine-based nucleoside analogues. It works by stopping the growth of tumor cells. Tipiracil is in a class of medications called thymidine phosphorylase inhibitors. It works by slowing the breakdown of trifluridine by the body. Giving tucatinib, trastuzumab, and TAS-102 together may work better than usual treatment for metastatic colorectal cancer.

Conditions

Metastatic Colon Adenocarcinoma; Metastatic Colorectal Adenocarcinoma; Metastatic Rectal Adenocarcinoma; Stage IV Colon Cancer AJCC V8; Stage IV Colorectal Cancer AJCC V8; Stage IV Rectal Cancer AJCC V8

Outcome Measures

Primary Outcomes (1)

• Progression-free survival rate

  Defined as progression-free and alive at the 2 months disease evaluation scan. Disease status will be assessed using Response Evaluation Critera in Solid Tumors (RECIST) version (v). 1.1. Evaluable patients are defined as those who are eligible, consented, and received any protocol treatment. A 95% confidence interval will be calculated using the method proposed by Koyama and Chen, 2008 and implemented with the R software package clinfun (RStudio, 2021; Venkatraman, 2018).

  At 2 months

Secondary Outcomes (4)

• Clinical benefit

  Up to 4 years

• Overall response

  Up to 4 years

• Overall survival (OS)

  From registration to death from any cause, assessed up to 4 years

• Incidence of adverse events

  Up to 4 years

Study Arms (1)

Treatment (tucatinib, trastuzumab, TAS-102)

EXPERIMENTAL

Patients receive tucatinib PO BID, trastuzumab IV over 30-90 minutes on days 1 and 15, and TAS-102 PO BID on days 1-5 and 8-12. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Biological: Trastuzumab; Drug: Trifluridine and Tipiracil Hydrochloride; Drug: Tucatinib

Interventions

Trastuzumab BIOLOGICAL

Given IV

Also known as: ABP 980, ALT02, Anti-c-ERB-2, Anti-c-erbB2 Monoclonal Antibody, Anti-ERB-2, Anti-erbB-2, Anti-erbB2 Monoclonal Antibody, Anti-HER2/c-erbB2 Monoclonal Antibody, Anti-p185-HER2, c-erb-2 Monoclonal Antibody, HER2 Monoclonal Antibody, Herceptin, Herceptin Biosimilar PF-05280014, Herceptin Trastuzumab Biosimilar PF-05280014, Herzuma, Kanjinti, MoAb HER2, Monoclonal Antibody c-erb-2, Monoclonal Antibody HER2, Ogivri, Ontruzant, PF-05280014, rhuMAb HER2, RO0452317, SB3, Trastuzumab Biosimilar ABP 980, Trastuzumab Biosimilar ALT02, trastuzumab biosimilar EG12014, Trastuzumab Biosimilar HLX02, Trastuzumab Biosimilar PF-05280014, Trastuzumab Biosimilar SB3, Trastuzumab Biosimilar SIBP-01, Trastuzumab-anns, Trastuzumab-dkst, Trastuzumab-dttb, Trastuzumab-pkrb, Trastuzumab-qyyp, Trazimera

Treatment (tucatinib, trastuzumab, TAS-102)

Trifluridine and Tipiracil Hydrochloride DRUG

Given PO

Also known as: Lonsurf, TAS 102, TAS-102, Tipiracil Hydrochloride Mixture with Trifluridine, Trifluridine/Tipiracil, Trifluridine/Tipiracil Hydrochloride Combination Agent TAS-102

Treatment (tucatinib, trastuzumab, TAS-102)

Tucatinib DRUG

Given PO

Also known as: ARRY-380, Irbinitinib, ONT-380, Tukysa

Treatment (tucatinib, trastuzumab, TAS-102)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Registered to COLOMATE ACCRU-GI-1611 and:
• COLOMATE Companion Trial Recommendation Form indicates patient meets molecular eligibility for enrollment to this study (at least one of the following: PIK3CA, KRAS, NRAS, or BRAF V600 mutation detected in blood from the Guardant360 assay)
• COLOMATE Companion Trial Recommendation Form date of completion is \< 90 days prior to registration
• Age \>= 18 years
• Histologically and/or cytologically confirmed metastatic adenocarcinoma of the colon or rectum
• Life expectancy \>= 3 months in the estimation of the investigator
• Previous treatment with or contraindication to:
• A fluoropyrimidine (e.g., 5-fluorouracil or capecitabine)
• Oxaliplatin
• Irinotecan
• An anti-VEGF biological therapy (including but not limited to bevacizumab, ramucirumab, or ziv-aflibercept)
• If the tumor has deficient mismatch repair proteins or is microsatellite instability (MSI)-High based on tumor tissue testing, an anti-PD-1 monoclonal antibody (nivolumab or pembrolizumab)
• (Cancer Therapy List \[colorectal cancer\] is available on the Academic and Community Cancer Research United \[ACCRU\] web site)
• Radiographically measurable disease as per Response Evaulation Criteria in Solid Tumors (RECIST) version 1.1
• Molecular testing result from Clinical Laboratory Improvement Act (CLIA)-certified laboratory confirming that the tumor tissue has at least one of the following:

You may not qualify if:

• Radiation therapy, hormonal therapy, biologic therapy, experimental therapy, or chemotherapy for cancer \< 21 days prior to registration
• Prior treatment with an anti-HER2 tyrosine kinase inhibitor, including but not limited to tucatinib, lapatinib, or neratinib
• Note: Prior treatment with an anti-HER2 antibody or antibody drug conjugate is permitted (including but not limited to trastuzumab, pertuzumab, fam-trastuzumab-deruxtecan-nxki, ado-trastuzumab emtansine)
• Prior treatment with TAS-102
• Concurrent severe and/or uncontrolled medical conditions which may compromise participation in the study, including impaired heart function or clinically significant heart disease
• Not recovered to baseline or Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0 =\< Grade 1 from toxicity due to all prior therapies except alopecia, oxaliplatin-related neuropathy, and clinically insignificant electrolyte abnormalities. Congestive heart failure (CHF) must have been =\< Grade 1 in severity at the time of occurrence and must have resolved completely prior to registration
• Female patients who are pregnant or breast feeding
• Currently taking medications specified by the protocol as prohibited for administration in combination with study drug
• Known active central nervous system (CNS) metastases (patients with radiated or resected lesions are permitted, provided the lesions are fully treated and inactive, patients are asymptomatic, and no steroids have been administered \>= 30 days prior to registration)
• Note: Steroids for treatment of other medical conditions other than CNS metastases are permitted
• Inability to swallow pills or any significant gastrointestinal disease which would preclude the adequate oral absorption of medications
• Use of a strong cytochrome P450 (CYP)2C8 inhibitor within 5 half-lives of the inhibitor or use of a strong CYP3A4 or CYP2C8 inducer within 5 days prior to registration
• Major surgical procedure, open biopsy, or significant traumatic injury =\< 28 days prior to registration (56 days for hepatectomy, open thoracotomy, major neurosurgery) or anticipation of need for major surgical procedure during the course of the study
• Serious, non-healing wound, ulcer, or bone fracture
• History of stroke (cerebrovascular accident), transient ischemic attack (TIA), myocardial infarction (MI), unstable angina, cardiac or other vascular stenting, angioplasty, or cardiac surgery =\< 6 months prior to registration

Sponsors & Collaborators

• Academic and Community Cancer Research United: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

UC San Diego Moores Cancer Center

San Diego, California, 92037, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Colonic Neoplasms; Rectal Neoplasms; Colorectal Neoplasms

Interventions

Trastuzumab; PF-05280014; Ogivri; Ontruzant; trastuzumab biosimilar HLX02; Trifluridine; trifluridine tipiracil drug combination; tucatinib

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• John H Strickler

  Academic and Community Cancer Research United

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2022
• First Posted: May 2, 2022
• Study Start: October 31, 2023
• Primary Completion: September 17, 2024
• Study Completion: September 17, 2024
• Last Updated: September 19, 2024

Record last verified: 2024-09

Locations

US (2)