Several new clinical trials in urologic cancers, including prostate cancer, have opened in recent months. Maybe one of your patients could benefit from taking part.
Metastatic castration-resistant prostate cancer. Patients with this diagnosis who have received one prior androgen receptor axis targeted therapy and one prior taxane-containing regimen can join a randomized phase 2/3, open-label study testing the investigational drug MGC018 (from Macrogenics). This is an antibody-drug conjugate that targets solid tumors expressing an immune checkpoint molecule called B7-H3. The trial has two stages. In the phase 2 stage, participants will receive one of two alternative doses of MGC018 or a comparator (abiraterone [Zytiga, Yonsa] or enzalutamide [Xtandi]) every 4 weeks. After an interim analysis at the 2-month point, the phase 3 part of the trial will start with a further 270 patients. These individuals will receive either the selected dose of MGC018 or a comparator every 4 weeks for up to 2 years. Sites in Florida and Louisiana started recruiting for 420 participants in November 2022. The outcome measure is radiographic progression-free survival (PFS). Overall survival (OS) is a secondary measure, and quality of life (QoL) will not be tracked. More details at clinicaltrials.gov
When ask to comment on this study, Marc Garnick, MD, professor of medicine, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, said that he could not find “any convincing scientific rationale” for studying MGC018 in this population. He warned that “patients should be made aware of other potential therapies that may be utilized in this clinical setting before participating in this study.”
Metastatic castration-resistant prostate cancer. People with this disease are eligible for an open-label phase 2 study testing another investigational antibody-drug conjugate, datopotamab deruxtecan (Dato-DXd, from AstraZeneca/Daiichi Sankyo). This drug takes aim at TROP2, an intracellular signaling protein that is boosted in many cancers and that controls cell proliferation and survival. Participants will receive intravenous (IV) Data-DXd either as monotherapy or in combination with the oral drug AZD5305, an investigational PARP inhibitor (also from AstraZeneca). Sites in California and Texas and also in Korea started recruiting for 531 participants across five types of solid cancer in September 2022. Research centers in nine more US states and 12 other countries are also gearing up to enroll patients into the trial. Objective response rate (ORR) and adverse event profile are primary endpoints. OS and QoL will not be tracked. More details at clinicaltrials.gov
Newly diagnosed prostate cancer without metastases. Adults with this type of prostate cancer who are planning to undergo stereotactic body radiation therapy (SBRT) can enter a phase 2, open-label National Cancer Institute study to see whether a radiotracer called 18F-DCFPyl can improve the ability of PET/CT scans to detect response to therapy. Participants will undergo MRI and PET/CT scanning at the start of SBRT treatment. They will receive an injection of 18FDCFPyl prior to the PET/CT scan. The scans will be repeated 8 weeks and 6 months after the start of SBRT and if the disease reappears within approximately 2 years. The trial opened in August 2022 at the National Institutes of Health Clinical Center in Bethesda, Maryland. The investigators are looking to enroll 120 participants. The sole outcome measure is imaging response to treatment. OS and QoL will not be assessed. More details at clinicaltrials.gov
Garnick commented: “This is a study of interest, as it will potentially expand the utility of [prostate-specific membrane antigen] scanning in the nonmetastatic setting and may help with more precise understanding of scan findings that do not definitely identify oligometastases.”
Prostate cancer patients eligible for androgen deprivation therapy (ADT). Adults in this position who can undergo ADT for at least 1 year are being recruited for a randomized, open-label phase 3 study comparing major adverse cardiovascular events (MACE) associated with the GnRH antagonist drugs relugolix (Orgovyx) and leuprolide acetate (Lupron). For up to 5 years, people in the trial will receive either daily tablets of relugolix or leuprolide as a 3- or 6-month depot injection. Study sites in Arizona, Florida, Illinois, Texas, and Virginia opened in December 2022 with the hope of recruiting 2250 participants. Time to a MACE within 5 years is the primary outcome. OS and QoL will not be measured. More details at clinicaltrials.gov
Garnick commented that this trial “was an important study, and hopefully it will provide an answer. However, its precursor study, PRONOUNCE, was inconclusive. It would have been a better study if a population enriched for patients with a prior history of MACE or with family members with a history of MACE were preferentially included. There may not be enough events. Also, having patients scored with an ACE27 baseline evaluation would be very instructive.”
Advanced papillary kidney cancer. Adult patients with this diagnosis can join a randomized, open-label, phase 2 National Cancer Institute study comparing the effectiveness of cabozantinib (Cabometyx, Cometriq) plus atezolizumab (Tecentriq) to cabozantinib alone. For up to 5 years or until disease progression or death, whichever occurs first, participants will take tablets of cabozantinib daily. Half the group will also receive IV atezolizumab every 3 weeks. Study centers in California, Illinois, Iowa, Michigan, Minnesota, and Ohio started recruiting 200 participants in September 2022. PFS is the primary endpoint, and OS is a secondary endpoint. QoL will not be recorded. More details at clinicaltrials.gov
Naive non-muscle-invasive bladder cancer (NMIBC). Adult patients with this cancer can join an open-label phase 3 National Cancer Institute trial comparing gold-standard bacillus Calmette-Guérin (BCG) treatment to GemDoce, a combination of gemcitabine (Gemzar) and docetaxel (Taxotere). Individuals in the GemDoce group will receive monthly instillations of the therapy into the bladder for up to 2 years after an initial induction period during which they will receive six weekly treatments. People receiving BCG will also start with six weekly instillations and will then receive weekly doses for 3 consecutive weeks at 3, 6, 12, 18, 24, 30, and 36 months. The Johns Hopkins Oncology Center began recruiting their planned 870 trial participants in December 2022. The primary outcome is event-free survival over 2 years. QoL is a secondary outcome, and OS will not be assessed. More details at clinicaltrials.gov
Garnick viewed the John’s Hopkins bladder cancer study as “the most important study” of the six new trials described in this article. Garnick said that the trial “represents the work of Dr Michael O’Donnell, whose work from the University of Iowa has changed the landscape of NMIBC with his GemDoce trials. This is an excellent study that may change 40-plus years of practice by enabling an alternative ― and a possibly better- tolerated alternative ― to intravesical BCG.” Garnick had this advice for the investigators: “The study should be modified to enable those on the GemDoce to continue for 3 years of maintenance if they continue to respond at the end of 2 years.”
All trial information is from the National Institutes of Health US National Library of Medicine (online at clinicaltrials.gov).
Garnick is editor-in-chief of the Harvard Medical School Annual Report on Prostate Diseases, for which he receives an honorarium.
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