New Gynecology Trials: Could Your Patient Benefit?

Several new studies on gynecologic conditions have started in recent months. Perhaps one of your patients would be interested?

Human papillomavirus (HPV) 16–positive, PD-L1–positive, persistent-recurrent or metastatic cervical cancer. Adults with this diagnosis who have progressed on standard first-line therapy of pembrolizumab (Keytruda) plus chemotherapy with/without bevacizumab (Avastin) may be eligible to join a phase 2, randomized, placebo-controlled study of an experimental vaccine called VB10.16. The vaccine targets tumors positive for HPV 16, one of the most common and oncogenic HPV types. All participants in the trial will receive up to 11 intramuscular administrations of VB10.16 over approximately 1 year using a needle-free injection system. One group will also be given intravenous (IV) infusions of saline solution as a placebo every 3 weeks, while other people will get 3-weekly infusions of atezolizumab (Tecentriq). Sites across 11 states started recruiting 130 participants in April 2024. The primary outcome is objective response rate (ORR). Overall survival over approximately 2 years is a secondary measure, and quality of life (QoL) is not assessed. More details at clinicaltrials.gov

Sarah Dilley, MD, MPH, FACOG, a gynecologic oncologist at the Winship Cancer Institute of Emory University, Atlanta, who is involved in this trial, said that effective treatment options for women in this situation are “seriously limited,” and that they are “often young, healthy women who are excellent candidates for a clinical trial.”

Dilley added, “It is exciting to have a potential treatment targeted specifically at HPV and could have implications for the treatment of other HPV-mediated cancers such as anal and oropharyngeal cancers.”

Recurrent or metastatic pembrolizumab-resistant cervical cancer. Women with this type of cancer whose tumors are positive for PD-L1 and HPV 16/18 may wish to consider another HPV vaccine study. This time, a randomized, open-label, phase 2 trial is looking at whether adding an experimental vaccine called PRGN-2009 to pembrolizumab is more effective than using pembrolizumab alone. PRGN-2009 targets HPV types 16 and 18, which together are responsible for around 70% cervical cancer. All participants in the study will receive IV infusions of pembrolizumab every 6 weeks. One group will also receive subcutaneous injections of PRGN-2009 every 3 weeks for the first 9 weeks, then every 6 weeks thereafter. Sites in Arkansas, Maryland, and Washington opened their doors to 46 participants in August 2024. ORR is the primary endpoint. Overall survival over 1 year is a secondary endpoint, and QoL is not being tracked. More details at clinicaltrials.gov

Dilley, who is not involved in this study, commented: “Phase 1 data showed promising efficacy of PRGN-2009 in combination with immune checkpoint inhibition, and I am hopeful that this trial will confirm those findings.”

Suspected, newly diagnosed, or recurrent epithelial ovarian cancer or suspected epithelial, peritoneal, or fallopian tube cancer. Adults with one of these types of cancer who are scheduled for surgery may be eligible to join a randomized, open-label, phase 3 study to determine how effectively a fluorescent imaging agent called aminolevulinic acid hydrochloride (Gleolan, Ameluz, and Levulan Kerastick) reveals ovarian tumor tissue during surgery. Aminolevulinic acid hydrochloride is selectively absorbed by cancer cells and metabolized to a form that glows red violet when doused in blue light. This increases the chances that the surgeon will see and resect all tumor cells, even those that have spread into the body cavity. The imaging agent Gleolan is only approved for glioma surgery, so the current trial could lead to a new indication. In this study, participants will take a one-time oral tablet of Gleolan and then undergo standard debulking surgery followed by blue light imaging. The surgical team will take biopsy samples throughout the procedure. The Luminis Health Anne Arundel Medical Center in Annapolis, Maryland, started seeking its 170 participants in May 2024. The primary outcome is the percentage of participants with one or more immunofluorescent lesions that were not caught during standard surgery but later proved to be cancerous by histopathology. The secondary outcome is the positive predictive value of the imaging agent. Overall survival and QoL will not be assessed. More details at clinicaltrials.gov

Primary, advanced, high-grade, serous/endometrioid epithelial ovarian, fallopian tube, or peritoneal cancer. Patients in one of these clinical situations who are scheduled for neoadjuvant chemotherapy followed by surgery may be interested in an open-label randomized, phase 2 investigation of an experimental radiotherapy called Radspherin. Radspherin is a suspension of alpha-emitting radioactive particles that is instilled into the targeted body cavity, thus, theoretically, minimizing radiation exposure of healthy tissues. It is also under investigation for peritoneal metastases in colorectal cancer. People in the current study will receive a single intraperitoneal injection of the radiotherapy suspension before their scheduled neoadjuvant chemotherapy and debulking surgery. Study sites in the United Kingdom, Norway, and Spain opened in June 2024, ready for 114 participants. Sites in Florida and Belgium are gearing up. Progression-free survival over 2 years is the primary outcome. Overall survival and QoL are not assessed. More details at clinicaltrials.gov

Recurrent, high-grade ovarian, primary peritoneal, and/or fallopian tube cancer. Adults with any of these cancers who have BRCA1/2 mutations and positive hormone receptor status and whose disease has progressed on a poly ADP ribose polymerase inhibitor are sought for a randomized, open-label phase 2 study. The study is designed to find out whether tuvusertib, an experimental inhibitor of ataxia telangiectasia and Rad3-related (ATR) kinase, can shrink tumors better if combined with existing therapy, niraparib (Zejula), or an experimental treatment called lartesertib, an ataxia telangiectasia–mutated (ATM) kinase inhibitor. Both ATR and ATM kinase inhibitors are designed to disrupt the DNA repair process in tumor cells. For up to approximately 3.5 years, one group of people in the study will take oral tablets of tuvusertib and niraparib. The others will take oral lartesertib instead of niraparib. Next Oncology in Fairfax, Virginia, began enrolling the trial’s 60 participants in August 2024. ORR and adverse events are the primary endpoints. The researchers are not tracking overall survival or QoL. More details at clinicaltrials.gov

Uterine leiomyomata not scheduled for surgery within 6 months. Premenopausal patients aged 21-53 years with symptomatic uterine fibroids are welcome to enroll in a randomized, placebo-controlled, phase 4 trial to see whether letrozole (Femara) can improve symptoms and shrink their fibroids. Letrozole, an oral aromatase inhibitor that suppresses the production of estrogen, is currently indicated for breast cancer in postmenopausal women. The hope is that lowering estrogen levels may shrink fibroid tissue: Small studies of aromatase inhibitors have shown some benefits in uterine fibroids. Using the same rationale, some physicians treat fibroids off-label with gonadotropin-releasing hormone receptor antagonists (leuprolide acetate [Lupron], nafarelin acetate [Synarel], and goserelin [Zoladex]). In this study, one group of participants will take daily tablets of letrozole for 12 weeks, while the other people take placebo capsules for 12 weeks and then letrozole tablets for 12 weeks. Study sites at the University of California San Francisco and the University of Mississippi Medical Center, Jackson, Mississippi, began welcoming their 140 participants in July 2024. The primary endpoint is patient-reported symptom severity. QoL and other patient-reported outcomes are secondary endpoints, along with objective measures such as change in uterine volume. More details at clinicaltrials.gov

All trial information is from the National Institutes of Health’s National Library of Medicine (online at clinicaltrials.gov).

Dilley is involved in the VB10.16 trial and declared no other conflicts of interest.