Several new clinical trials in gynecological cancers have opened in recent months. Maybe one of your patients could benefit from taking part?
Advanced or metastatic gynecological cancers, or recurrent endometrial, fallopian tube, or ovarian cancer. Patients with one of these diagnoses who have progressed on one line of standard systemic therapy or have run out of options to prolong survival can now join the National Cancer Institute’s ComboMATCH screening trial that attempts to match tumor genetics to an appropriate treatment. This study is the gateway to the ComboMATCH suite of phase 2 treatment trials. Sites in 23 states and Puerto Rico started recruiting in March 2023 for 2900 participants with a solid tumor. The primary outcome of this screening trial focuses on recruitment success for the treatment trials, for example, accrual over 8 years. The secondary outcome measure looks ahead to the treatment trials and is “rate of positive outcomes.” The definition of positive outcome depends on the patient’s assigned treatment but is most commonly progression-free survival (PFS) or overall response rate (ORR). More details at clinicaltrials.gov.
Approached for comment, Maurie Markman, MD, president of Medicine and Science at City of Hope, who is not involved in this trial, explained that ComboMATCH is “examining a number of combination targeted agents, or a targeted agent plus chemotherapy, in multiple clinical settings based on pre-clinical evaluation.”
Recurrent or persistent endometrial or ovarian cancer with a RAS mutation. Adults in this situation who have progressed after first-line treatment for recurrent or persistent disease may be eligible for a ComboMATCH treatment trial to see if adding olaparib (Lynparza) to selumetinib (Koselugo) increases the chance that the tumor remains stable or shrinks. Olaparib inhibits PARP, an enzyme that helps cells, including tumor cells, repair damaged DNA, while selumetinib is a selective inhibitor of mitogen activated protein kinase kinases 1 and 2 (MEK 1/2). One group of participants will take tablets or capsules of both selumetinib and olaparib every day; the other group will take selumetinib only. People whose tumors progress on selumetinib will have the option to add olaparib. The study opened in March 2023 across 13 states, looking for 165 participants. The primary outcome measure is progression-free survival. Overall survival (OS) and quality of life (QoL) will not be assessed. More details at clinicaltrials.gov.
Markman commented: “[This is] an interesting phase 2 trial comparing targeted agents based on the presence of RAS mutation in recurrent or persistent endometrial or ovarian cancer…based on preclinical data suggesting the favorable impact of this strategy in these gynecologic malignancies.”
Advanced, metastatic, or recurrent grade 1 or 2 endometrial cancer. Post-menopausal women with these types of cancer who have not received treatment in this setting can join a randomized, blinded, phase 3 study studying the advantage of adding the investigational agent lerociclib (from EZRx) to letrozole (Femara). Lerociclib is an inhibitor of cyclin-dependent kinases 4 and 6 (CDK 4/6), enzymes that regulate the cell cycle. The drug is also being tested in breast cancer and lung cancer. Participants will take a daily, oral combination of either letrozole plus lerociclib, or letrozole plus placebo. Study sites in Florida, Nevada, New Mexico, and Ohio opened in April 2023, ready for 320 participants. Progression-free survival is the primary outcome. OS and QoL are secondary measures. More details at clinicaltrials.gov.
Recurrent ovarian, fallopian tube, or primary peritoneal cancer. Adult women with these diagnoses are eligible for a randomized National Cancer Institute phase 2 study to see whether the investigational agent CDX-1140 prolongs survival when added to pembrolizumab (Keytruda) and bevacizumab (Avastin). CDX-1140 is a novel agonist CD40 antibody, which can lead to apoptosis and impaired growth of cancer cells due to direct signaling effects. In this trial, all participants will receive pembrolizumab and bevacizumab by intravenous (IV) infusion every 3 weeks, and those in the experimental group will have CDX-1140 added to the mix. Treatment will be continued until disease progression or unacceptable toxicity. Sites in New York and Texas plan to start recruiting 80 participants at the end of June 2023. Incidence of adverse events and objective response rate are the primary endpoints. OS and QoL are secondary endpoints. More details at clinicaltrials.gov.
Advanced ovarian cancer. Patients aged 18-70 with this diagnosis who have not responded to first-line treatments for their advanced disease are eligible for a phase 2 National Cancer Institute study testing autologous T-cell receptor (TCR) gene therapy. Unlike CAR T-cell therapy, which only reaches the 20% of cancer neoantigens that are expressed extracellularly, TCR technology can target the 80% of abnormal proteins that are expressed inside cancer cells. Participants will receive a single infusion of their own engineered T cells. If their tumor responds, they will attend follow-up visits every 3-6 months for 3 years, then join a long-term study in which they will be followed for 12 more years. The National Institutes of Health’s Clinical Center in Bethesda, Maryland, began welcoming its 210 participants with one of a range of cancers in June 2023. Response rate, measured by objective tumor regression, is the primary endpoint. OS and QoL will not be tracked. More details at clinicaltrials.gov.
Advanced cervical cancer. Adults with this cancer who are eligible for definitive chemoradiotherapy can join a randomized, open-label, phase 2 National Cancer Institute trial to find out whether adding novel radiosensitizer telaglenastat (from Calithera Biosciences) can slow down tumor progression. Telaglenastat is an investigational, first-in-class, selective, oral glutaminase inhibitor. Many tumor cells need glutaminase to repair damage after exposure to ionizing radiation so the hope is that glutaminase inhibition will boost the effects of radiotherapy by “radiosensitizing” the tumor. In this trial, all participants will receive standard-of-care chemoradiation over 7 weeks. In addition, one group will take twice-daily oral telaglenastat, beginning 2 weeks before the radiation starts. The research site at the Washington University School of Medicine, St. Louis, Missouri, opened its doors to 42 participants in May 2023. Progression-free survival is the primary endpoint, OS is a secondary endpoint, and QoL is not recorded. More details at clinicaltrials.gov.
All trial information is from the National Institutes of Health US National Library of Medicine (online at clinicaltrials.gov).
Markman has no involvement with any of these trials. He is a regular contributor to Medscape Oncology and reports relationships with Genentech, AstraZeneca, Celgene, Clovis, and Amgen.
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