New Trials in GI Cancers (Non-CRC): Could Your Patient Benefit?

Helen Leask

November 30, 2021

A number of clinical trials in noncolorectal gastrointestinal cancers have opened in recent months. Maybe one of your patients could benefit from being enrolled?

Locally advanced or metastatic hepatocellular carcinoma (HCC). Adult patients with biopsy-proven advanced hepatocellular cancer who have failed on two systemic therapies are sought for a phase 2 trial testing an electromagnetic treatment device called TheraBionic. Participants will have a 1-hour session with the device at the cancer center, then will take the device home and self-administer three 1-hour treatments a day for up to 2 years, with clinic visits every 6 weeks.

Those randomly assigned to the control group will use a device that does not emit therapeutic frequencies. The study started recruiting in November and hopes to enrol 166 participants. US trial centers are in Arizona, Illinois, and North Carolina. Overall survival (OS) and quality of life (QoL) are the primary outcome measures. More details at

Mark Lewis, MD, director of GI oncology at Intermountain Healthcare in Murray, Utah, and a regular Medscape contributor, was approached for comment on this study. "Later-line therapies for HCC are often limited in their clinical eligibility," he said, "so this study's inclusion of up to Child's Pugh Class B9 and its testing of a nonpharmacologic intervention are appealing."

Advanced-stage unresectable biliary-tract cancer (BTC). Adult patients with this cancer who have received at least one prior systemic therapy — no more than two in the metastatic setting — are being recruited for a National Cancer Institute (NCI) phase 2 study testing two immune therapies with and without a MEK inhibitor, cobimetinib (Cotellic). All participants will receive the checkpoint inhibitor atezolizumab (Tecentriq) and the experimental drug varlilumab, a novel, first-in-class agonist immunoglobulin G1 anti-CD27 antibody.

These two immunotherapies will be administered by intravenous infusions every 2 weeks until disease progression or unacceptable toxicity, for up to 1 year. One group will also take daily oral cobimetinib for 3 out of 4 weeks. The trial began recruiting for 64 participants on September 15 at the JHU Sidney Kimmel Comprehensive Cancer Center in Baltimore. Primary outcomes are overall response rate (ORR) and progression-free survival (PFS). OS is a secondary outcome and QoL is not tracked. More details at

Lewis commented: "Few GI malignancies have seen their therapeutic paradigm shift more in recent years than biliary tract cancers, but immunotherapy and MEK inhibition have yet to yield the same dividends in BTC as they have in melanoma."

Advanced hepatocellular carcinoma, pancreatic ductal adenocarcinoma (PDAC) and biliary tract cancer. Patients with these advanced unresectable or metastatic tumors that have progressed while on, or since finishing, the last treatment can join a phase 2 study assessing a three-drug combination of immunotherapy pembrolizumab (Keytruda), belzutifan (Welireg), an HIF-2a inhibitor, and kinase-inhibitor lenvatinib (Lenvima).

Each participant will take a belzutifan tablet and lenvatinib capsule daily until disease progression or discontinuation and receive intravenous pembrolizumab once every 6 weeks for up to 2 years. Investigators are aiming to enroll 30 participants for each tumor type; an additional 70 people with each type of tumor may join the study later if the interim analysis is favourable. US sites opened on August 18 in California and North Carolina. Toxicity and ORR are the primary outcomes. OS is a secondary outcome and QoL is not measured. More details at

"This tripartite approach aims to target multiple pathways simultaneously in a histology-agnostic fashion," said Lewis.

Advanced pheochromocytoma/paraganglioma (PPGL) or pancreatic neuroendocrine tumor (pNET). Patients with these cancers can join another phase 2 study testing the performance of HIF-2a inhibitor belzutifan, this time as a monotherapy. Participants will take a once-daily tablet of belzutifan until they choose to discontinue or their diseases progress for up to approximately 4 years. The study opened to 140 participants on August 12 in 25 locations in Europe, Turkey, Russia and the US (California, Maryland, Tennessee, Texas). Response rate is the primary outcome. OS over 4 years is a secondary outcome. QoL will not be assessed. More details at

Lewis observed: "The August 2021 FDA approval of belzutifan for vHL [Von Hippel-Lindau syndrome]-associated tumors was a landmark in the treatment of hereditary cancer syndromes and it's plausible that the drug's mechanism of action can be used to exploit other tumors with deranged angiogenesis."

Gastroesophageal cancer that has progressed after standard treatment. Adults with this cancer who have progressed despite two or more treatments for recurrent/metastatic disease — including at least one platinum agent and one fluoropyrimidine analog — are being recruited for a phase 3 study comparing a combination of regorafenib (Stivarga) and nivolumab (Opdivo) to standard-of-care chemotherapy. Participants in the experimental arm will self-inject regorafenib 3 weeks out of 4 for up to 5 years or until unacceptable toxicity or disease progression, whichever happens first.

This group will also receive intravenous nivolumab approximately twice a month, dropping to once-monthly treatments after 2 months if the disease is controlled. OS is the primary outcome; QoL is a secondary measure. The study opened on June 1 seeking 450 participants worldwide. US sites are in Arizona, California, Minnesota, and Ohio. More details at

Lewis said: "Regorafenib has seen second life after the ReDOS trial established a more effective dose-escalation strategy to allow for longer therapeutic courses in refractory colon cancer. Now its combination with nivolumab is particularly timely as immunotherapy has achieved frontline prominence in the wake of CheckMate 648 and 649."

Metastatic gastric or gastroesophageal-junction (GEJ) cancers. Patients with these cancers that have progressed despite standard chemotherapy (containing either trastuzumab or fluoropyrimidine plus platinum) are sought for an NCI phase 2 trial comparing two therapy combinations. For up to approximately 2.5 years or until disease progression or unacceptable toxicity, whichever occurs first, one group of participants will receive intravenous ramucirumab (Cyramza) once every 2 weeks and take twice-daily tablets of trifluridine plus tipiracil (Lonsurf).

The other group will be given weekly intravenous paclitaxel (Taxol) for 3 out of 4 weeks and ramucirumab every 2 weeks. Progression-free survival is the primary outcome, with OS and QoL as secondary outcomes. Investigators hope to attract 116 participants. Sites in Arizona, California, Florida, Kansas, and Wisconsin opened on June 16, with centers in Illinois, Iowa, Minnesota, and Nebraska to follow. More details at

"Ramucirumab/paclitaxel is already a standard-of-care doublet in later-line treatment of G/GEJ cancer but the combination of ramucirumab with trifluridine/tipiracil may be particularly palatable to patients with neuropathy after first-line platinum exposure," Lewis commented.

All trial information is from the National Institutes of Health US National Library of Medicine (online at

Lewis reports no relevant financial relationships. He is a regular contributor to Medscape with the "Lewis on Oncology" column.

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