New Trials in GI Cancers: Could Your Patient Benefit?

Several clinical trials in noncolorectal gastrointestinal cancer have started recently. Perhaps one of your patients is eligible to take part?

Child-Pugh A or B Advanced Hepatocellular Carcinoma

Adult patients with this type of liver cancer may be eligible for a randomized placebo-controlled phase 2/3 study by the National Cancer Institute (NCI) evaluating whether a device called TheraBionic can improve survival. TheraBionic floods the body with low levels of radiofrequency electromagnetic fields through a spoon-shaped antenna held in the patient's mouth. Following one demonstration treatment at the study center, participants use TheraBionic at home three times a day for up to 6 months. One group of participants will use a device programmed with radio frequencies known to be effective against hepatocellular carcinoma. A second group will use a placebo device that does not emit therapeutic frequencies.

Recruitment of the trial's 166 participants started in July 2023 at Wake Forest Baptist Comprehensive Cancer Center in Winston-Salem, North Carolina. Sites in Florida, Illinois, Oregon, Pennsylvania, and Texas are also planned. Overall survival at 6 months and quality of life (QOL) are the primary endpoints. More details at clinicaltrials.gov

The main advantage of the approach is that it is "unlikely to have major side effects in patients whose liver function and overall health often limit their opportunities to enroll in studies of experimental drugs," said Richard Goldberg, MD, professor emeritus at West Virginia University Cancer Institute, who is not involved in the research. Despite "a limited track record" for the science, Goldberg noted this NCI-supported study must have survived peer review.

Advanced Biliary-Tract Cancers

Adults with one of these cancers who are not eligible for locoregional therapy are sought for an open-label, phase 3 trial exploring how well patients tolerate the immunotherapy durvalumab (Imfinzi) alongside standard gemcitabine-based chemotherapy. Trial participants will receive one of seven gemcitabine-based chemotherapy regimens every 2 or 3 weeks for up to eight cycles or until discontinuation due to toxicities, whichever happens first. At the same time, each patient will receive intravenous durvalumab every 3 or 4 weeks. After eight cycles or premature discontinuation of chemotherapy, all participants will be offered ongoing durvalumab every 4 weeks — with or without additional chemotherapy — at the investigator's discretion.

The trial, with a planned enrollment of 160 participants, opened in August 2023 in a center in South Korea, and will soon be joined by sites in Japan, Singapore, Europe, Alabama, California, District of Columbia, New York, Oklahoma, and Oregon. The primary outcome is number of patients with a Grade 3 or 4 adverse event that may be drug-related. Secondary outcomes include overall survival and QOL. More details at clinicaltrials.gov

Primary Biliary Cholangitis and Compensated Cirrhosis

Adult patients younger than 76 years old with this risk factor for liver cancer can join a randomized, double-blind, placebo-controlled phase 3 study to determine if seladelpar (CymaBay Therapeutics) can delay death, liver transplantation, and other key measures of progression. Seladelpar is a first-in-class oral experimental therapy that selectively inhibits peroxisome proliferator-activated receptor delta, a regulator of critical disease-related metabolic pathways.

For up to 36 months, participants will take a daily capsule of seladelpar or a placebo. Sites in California, Florida, Kentucky, Maryland, Ohio, Texas, Virginia, and Washington opened their doors in September 2023 and are seeking 192 participants. Event-free survival is the primary outcome and overall survival is a secondary measure. QOL is not being tracked. More details at clinicaltrials.gov

Untreated, Unresectable Locally Advanced or Metastatic Hepatocellular Carcinoma

Patients with this cancer may be eligible to participate in a randomized, double-blind, placebo-controlled phase 3 trial to see whether an experimental immunotherapy called tiragolumab boosts the effectiveness of standard immunotherapy with atezolizumab (Tecentriq) plus bevacizumab (Avastin). One group will receive an IV infusion of atezolizumab and bevacizumab (Avastin) plus tiragolumab every 3 weeks until unacceptable toxicity or loss of clinical benefit; the other group will receive placebo in place of tiragolumab.

Centers worldwide and across the United States (California, Kentucky, Maryland, Missouri, Texas, and Washington) started recruiting 650 trial participants in September 2023. Overall survival is a primary outcome; QOL is a secondary endpoint. More details at clinicaltrials.gov

Goldberg said the study "provides access to a promising new anticancer antibody added to a standard therapy approach that avoids the potential side effects of chemotherapy" as all three agents are nonchemotherapy drugs.

Intermediate-Stage Hepatocellular Carcinoma

Adults with this type of cancer who have not yet received systemic or locoregional therapy may be eligible for a randomized, open-label phase 3 study testing a combination of pembrolizumab (Keytruda) and regorafenib (Stivarga) against standard therapy with transarterial chemoembolization (TACE) or transarterial radioembolization (TARE). One group of participants will receive oral regorafenib 3 weeks out of 4 plus IV pembrolizumab every 6 weeks until disease progression, unacceptable toxicity, deterioration of the patient's condition, or another reason for discontinuation. The other groups will receive TACE or TARE on demand, as per the site's standard protocol. UCLA Santa Monica Hematology Oncology started recruiting 496 participants in October 2023. The primary outcome is progression-free survival. QOL and overall survival are secondary outcomes. More details at clinicaltrials.gov

Goldberg commented that "this trial gives patients access to two approaches that are known to be effective to understand how best to sequence the complementary approaches."

Resected Pancreatic Ductal Adenocarcinoma

Adults facing this clinical scenario who have not received prior anticancer treatment can join an open-label, randomized phase 2 study of the effectiveness of autogene cevumeran (Genentech) plus atezolizumab and chemotherapy as adjuvant therapy versus chemotherapy alone. Autogene cevumeran is a patient-specific cancer vaccine encoding up to 20 patient-specific cancer mutations. The comparator group will receive IV modified FOLFIRINOX at specific time points while participants in the experimental treatment group will receive IV infusion of the triple-therapy combination.

Centers in Massachusetts, New Jersey, New York, and Rhode Island began enrolling the planned 260 trial participants in October 2023. The primary outcome is disease-free survival. Overall survival over 6 years is a secondary outcome and QOL is not being measured. More details at clinicaltrials.gov

"This study adds a vaccine that engages the immune system to standard therapy that has efficacy in pancreatic cancer to determine if the addition of the vaccine augments the other agents," said Goldberg. "It is a novel approach that is not likely to add significant side effects to the other agents employed in the standard multidrug regimen."

All trial information is from the National Institutes of Health US National Library of Medicine (online at clinicaltrials.gov). Goldberg was not involved with any of these trials.

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