Moffitt logo

COVID-19 Update: See the latest on our visitor policy here. Learn More

Clinical Trials Search

Clinical Trial 21201

Cancer Type: Gastrointestinal Tumor
Study Type: Treatment
NCT#: NCT04430738

Phase: Phase I/II
Principal Investigator: Sahin, Ibrahim

Call 813-745-6100
or 1-800-679-0775 Learn More
Overview

Study Title

A Phase 1b/2 Dose Escalation and Expansion Study of Tucatinib in Combination with Trastuzumab and Oxaliplatin-Based Chemotherapy for HER2+ Gastrointestinal Cancers

Summary

This trial studies tucatinib to find out if it is safe when given with trastuzumab and other anti-cancer drugs (pembrolizumab, 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.

Objective

Phase 1b Tucatinib Dose Escalation With Oxaliplatin-based Chemotherapy Primary: To determine the recommended dose of tucatinib when combined with trastuzumab and oxaliplatin-based chemotherapy (FOLFOX or CAPOX) in subjects with HER2+ gastrointestinal cancers Secondary: - To evaluate the safety and tolerability of tucatinib in combination with trastuzumab and oxaliplatin-based chemotherapy - To evaluate the combination of tucatinib, trastuzumab, and oxaliplatin-based chemotherapy for potential nephrotoxicity - To evaluate the PK of tucatinib - To evaluate the PK of oxaliplatin in the presence and absence of tucatinib Exploratory: - To evaluate the antitumor activity of tucatinib in combination with trastuzumab and oxaliplatin-based chemotherapy - To explore correlations between tissue and blood-based biomarkers and clinical outcomes Phase 2 Tumor Specific Expansion Primary: To evaluate the safety and tolerability of tucatinib combined with trastuzumab and oxaliplatin-based chemotherapy in subjects with 1L gastric, esophageal, and GEJ adenocarcinoma (FOLFOX or CAPOX) and in subjects with 1L+ CRC (FOLFOX) Secondary: - To evaluate the anti-tumor activity of tucatinib combined with trastuzumab and oxaliplatin-based chemotherapy (FOLFOX or CAPOX) in 1L gastric, esophageal, and GEJ adenocarcinoma as measured by confirmed objective response rate (cORR), according to RECIST v1.1, per investigator assessment (INV) - To evaluate the anti-tumor activity of tucatinib combined with trastuzumab and oxaliplatin-based chemotherapy in 1L gastric, esophageal, and GEJ adenocarcinoma as measured by duration of response (DOR) according to RECIST v1.1 per INV - To evaluate the anti-tumor activity of tucatinib combined with trastuzumab and oxaliplatin-based chemotherapy in 1L gastric, esophageal, and GEJ adenocarcinoma as measured by progression -free survival (PFS) according to RECIST v1.1 per INV - To evaluate the anti-tumor activity of tucatinib combined with trastuzumab and oxaliplatin-based chemotherapy in 1L gastric, esophageal, and GEJ adenocarcinoma as measured by overall survival (OS) - To evaluate the PK of tucatinib given with trastuzumab and oxaliplatin-based chemotherapy in subjects with 1L+ CRC and 1L gastric, esophageal, and GEJ adenocarcinoma Exploratory: - To evaluate the anti-tumor activity of tucatinib combined with trastuzumab and oxaliplatin-based chemotherapy (FOLFOX) in 1L+ CRC as measured by cORR, according to RECIST v1.1 per INV - To evaluate the anti-tumor activity of tucatinib combined with trastuzumab and oxaliplatin-based chemotherapy in 1L+ CRC as measured by DOR according to RECIST v1.1 per INV - To evaluate the anti-tumor activity of tucatinib combined with trastuzumab and oxaliplatin-based chemotherapy in 1L+ CRC as measured by PFS according to RECIST v1.1 per INV - To evaluate the anti-tumor activity of tucatinib combined with trastuzumab and oxaliplatin-based chemotherapy in 1L+ CRC as measured by OS - To explore correlations between tissue and blood-based biomarkers and clinical outcomes

Treatments

Therapies

Therapy (NOS)

Medications

5-fluorouracil (); CAPOX (); FOLFOX6 (); Herceptin (Trastuzumab); Oxaliplatin (); Pembrolizumab (Keytruda); Trastuzumab (); Tucatinib (); Xeloda (capecitabine); capecitabine (); eloxatin (Oxaliplatin); leucovorin (); rhuMAb HER2 (Trastuzumab)

Inclusion Criteria

  • Participants must have an unresectable or metastatic solid malignancy that is histologically or cytologically confirmed to be one of the tumor types listed below:
  • Cohorts 1A, 1B, 1C, and 1D
  • CRC
  • Gastric adenocarcinoma
  • GEJ adenocarcinoma
  • Esophageal adenocarcinoma
  • Cholangiocarcinoma
  • Gallbladder carcinoma
  • Cohorts 1E, 1F, 1G, and 2A
  • Gastric adenocarcinoma
  • GEJ adenocarcinoma
  • Esophageal adenocarcinoma
  • Cohort 2B
  • CRC
  • Participants must be candidates to receive an oxaliplatin-based regimen as part of their standard-of-care treatment for all cohorts, except Cohort 1G.
  • HER2+ disease, as determined by historic or local laboratory testing
  • 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.
  • Other criteria apply

  • Exclusion Criteria

  • History of known hypersensitivity to planned study treatment
  • Known to be positive for Hepatitis B or C
  • For Cohorts 2A and 2B: prior anti-HER2 therapies
  • For Cohorts 1E, 1F, 1G, 2A: Prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137), and was discontinued from that treatment due to a Grade 3 or higher immune-related adverse event (irAE)
  • Other criteria apply

  • If you are interested in learning more about clinical trials, our clinical trial navigators can discuss your options and recommend opportunities that may be suitable for you. Call 813-745-6100 or 1-800-679-0775 (toll-free) or submit a clinical trials inquiry form.