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Targeted therapies are the focus of new studies for colorectal and bile duct cancers

Published Date
Author Earle A. Chiles Research Institute

The Earle A. Chiles Research Institute, a division of Providence Cancer Institute of Oregon, is the only site in Oregon enrolling patients with human epidermal growth factor receptor 2 positive (HER2+) colorectal cancer in a new phase III trial. The study will evaluate the efficacy and tolerability of investigational oral medication tucatinib with other cancer drugs. If the outcome of the study establishes the combination of medications as part of standard care for HER2+ colorectal cancer, it may become an early line therapy for more patients. 

FDA accelerated approval

The study follows on the heels of the phase II MOUNTAINEER trial that showed a positive response rate to tucatinib plus trastuzumab in 84 patients with colorectal cancer. The combination of tucatinib and trastuzumab was well tolerated by trial participants and showed high and prolonged response rates.

The outcome of MOUNTAINEER informed the decision by the U.S. Food and Drug Administration (FDA) to grant accelerated approval to tucatinib in combination with trastuzumab for treating RAS wild-type HER2+ positive colorectal cancer that has metastasized, cannot be removed by surgery and has progressed on all standard chemotherapy regimens.

In the MOUNTAINEER study, diarrhea, fatigue and hypertension were the most common adverse effects of treatment. This latest study, known as MOUNTAINEER-03, also will evaluate the side effects of tucatinib in combination with trastuzumab and with chemotherapy mFOLFOX6 compared to standard treatment.

A first-line targeted therapy for HER2+ cancers

MOUNTAINEER-03 is designed with an experimental arm that includes tucatinib plus trastuzumab and mFOLFOX6 (fluorouracil, leucovorin and oxaliplatin). The current FDA approval for tucatinib with trastuzumab is for patients whose cancer has progressed following all standard chemotherapy regimens.

  • Tucatinib is a targeted therapy that identifies and attacks the HER2 tyrosine kinase (a family of enzymes) that contribute to cancer growth. It is given as a treatment regimen with trastuzumab and other cancer medications for patients with metastasized HER2+ breast cancer.  
  • Trastuzumab is humanized monoclonal antibody that also targets HER2+ cancers. It has been approved by the FDA to treat certain types of cancers but isn’t approved as treatment for colorectal or rectum cancer and is investigational in this study.

The standard care arm of the study includes mFOLFOX6 alone, mFOLFOX6 with bevacizumab or mFOLFOX6 with cetuximab. mFOLFOX6, bevacizumab and cetuximab are chemotherapies used to treat colorectal cancer.

The principal investigator of this global trial is Gina Vaccaro, M.D., medical director of Gastrointestinal Cancer Research at Providence Cancer Institute.

Find out more about MOUNTAINEER-03: Phase III study of tucatinib in combination with trastuzumab and mFOLFOX6 versus standard chemotherapy regimen for patients with HER2+ metastatic colorectal cancer

To refer a patient to this study or other clinical trials, contact our clinical research office:  

National accreditation for colorectal cancer care

Providence Colorectal Cancer Program includes a team of experts in colorectal cancer prevention and treatment. Medical oncologists, radiation oncologists, surgeons, scientists and other oncology professionals collaborate under one roof, providing coordinated, multidisciplinary care based on the latest research. Patients also have access to investigator-initiated and global clinical trials. In June 2021, Providence earned accreditation from the National Accreditation Program for Rectal Cancer (NAPRC). Providence Portland and Providence St. Vincent medical centers were the first in the Pacific Northwest and among the first 25 in the nation to earn this honor.

New study will evaluate TT-00420 for treating bile duct cancer

A clinical trial open to patients with cholangiocarcinoma is evaluating the safety and efficacy of a spectrum selective kinase inhibitor called TT-00420. The new medication received fast-track designation for treating cholangiocarcinoma by the FDA in late 2021 after promising clinical results in a phase I study that enrolled and treated nine patients with cholangiocarcinoma.

Earle A. Chiles Research Institute is offering this study for patients with metastatic cholangiocarcinoma that can’t be removed by surgery.  

Poor prognosis for most cholangiocarcinoma diagnoses

Cholangiocarcinoma is a rare type of cancer that starts in the bile ducts and generally has a poor prognosis. The 5-year survival rate for extrahepatic bile duct cancer, which forms in the bile ducts outside the liver, ranges from 2 to 17%, depending on the stage and whether it has spread to other parts of the body. Intrahepatic bile duct cancer forms in the bile ducts inside the liver and has a 5-year survival rate ranging from 2 to 25%.  

Treatment options for the disease vary depending on the type and stage of cancer, and whether it has spread. Surgery is an option for some patients if the cancer can be removed and is combined with chemotherapy or radiation therapy after surgery to kill remaining cancer cells. However, for some patients with unresectable cancer, immunotherapy or a targeted therapy, such as TT-00420, may be the best option.

TT-00420 targets FGFR2 mutations

In this phase II clinical trial, TT-00420, which is administered in tablet form, will be evaluated in four cohorts that include patients with:

  • FGFR2 fusions (mutation) who didn’t respond to prior FGFR inhibitor treatment
  • FGFR2 fusions who responded to prior FGFR inhibitor treatment
  • Other FGFR gene alterations
  • Tumors that do not contain a detectable FGFR alteration

FGFR2 is a gene involved in cell maturation and division, and the formation of new blood vessels and bone growth. A mutation in the gene may cause the FGFR2 protein to become overactive in certain cancers, such as cholangiocarcinoma. TT-00420 has shown to be effective in targeting a variety of FGFR2 mutations in preclinical studies.

Providence Cancer Institute is offering this trial to eligible participants. Gina Vaccaro, M.D., medical director of Gastrointestinal Cancer Research at Providence Cancer Institute is the principal investigator.

Find out more: Study to Evaluate the Efficacy and Safety of TT-00420 in Cholangiocarcinoma

To refer a patient to this study or other clinical trials, contact our clinical research office:  

Groundbreaking treatments and care

The Providence Hepatobiliary and Pancreatic Cancer Program cares for patients with disorders of the liver, bile ducts, gallbladder and pancreas. Our multidisciplinary approach to treatment incorporates the expertise of hepatobiliary surgeons, interventional radiologists, medical oncologists, radiation oncologists, social workers and other professionals. The team is highly engaged in patient care, meeting weekly to discuss and recommend treatment plans, new therapies based on the latest research and clinical trials.

New research studies are regularly posted to our site. Visit:

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