Clinical Trials

Phase 1/2 Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of BLU-222 as a Single Agent and in Combination Therapy for Patients With Advanced Solid Tumors

This is a Phase 1/2, open-label, first-in-human (FIH) study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and anticancer activity of BLU-222, a selective inhibitor of CDK2.

Study Contact:
Blueprint Medicines
617-714-6707
medinfo@blueprintmedicines.com

Immunotherapy has gained a significant amount of attention recently, but its efficacy as a single agent in gynecological cancers has been disappointing. Pre-clinical evidence supports the combination of using Vascular Endothelial Growth Factors (VEGF) inhibitors with immunotherapy. VEGF inhibitors suppress the activation of tumor-associated macrophages (TAMs) and VEGF has been shown to affect the functional maturation of dendritic cells; therefore, VEGF inhibitors could improve the function of antigen presentation. In this study, Cabozantinib (VEGF inhibitor) and Dostarlimab (immunotherapeutic drug) will be administered as a combination to patients with recurrent gynecologic carcinosarcoma.

Study Contact:
Anna Wilbanks, MSN, RN, WHNP-BC
Research Nurse Manager, GYN Oncology Clinical Trials
O’Neal Comprehensive Cancer Center
UAB | The University of Alabama at Birmingham
1700 6th Avenue South, Suite 10100, 10th Fl WIC | Birmingham, AL 35233

A Phase II/III Study of Paciltaxel/Carboplatin alone, or combined with either Trastuzumab and Hyaluronidase-oysk (HERCEPTIN HYLECTA), or combined with Trastuzumab and Hyaluronidase-zzfx (PHESCO) in HER2 Positive, Stage I-IV Endometrial Serous Carcinoma OR Endometrial Carcinosarcoma.

Sponsor: NRG, Sponsor Study ID: GY026
NCT Number: NCT05256225
Phase: II/III
Protocol Type: Treatment
Age Group: Adults

Study Objectives: This Phase II/III trial tests whether adding Trastuzumab and Hyaluronidase-cysk, OR, Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf to the usual chemotherapy (Pacitaxel and Carboplatin) works to shrink tumors in patients with HER2 positive Endometrial Serous Carcinoma or Endometrial Carcinosarcoma.
Study Documents: (https://portal.musc.edu/hcc/cto/WebDocs/103749).

The MUSC Resource telephone number to call about this study is: 843-985-0580.

Please see the National Institute of Health’s ClinicalTrials.gov site for more information.

This phase III randomized trial (NCT00954174) tested the null hypothesis that paclitaxel and carboplatin (PC) is inferior to paclitaxel and ifosfamide (PI) for treating uterine carcinosarcoma (UCS).

Adults with chemotherapy-naïve UCS or ovarian carcinosarcoma (OCS) were randomly assigned to PC or PI with 3-week cycles for 6-10 cycles. With 264 events in patients with UCS, the power for an overall survival (OS) hybrid noninferiority design was 80% for a null hazard ratio (HR) of 1.2 against a 13% greater death rate on PI with a type I error of 5% for a one-tailed test.

The study enrolled 536 patients with UCS and 101 patients with OCS, with 449 and 90 eligible, respectively. Primary analysis was on patients with UCS, distributed as follows: 40% stage I, 6% stage II, 31% stage III, 15% stage IV, and 8% recurrent. Among eligible patients with UCS, PC was assigned to 228 and PI to 221. PC was not inferior to PI. The median OS was 37 versus 29 months (HR = 0.87; 90% CI, 0.70 to 1.075; P < .01 for noninferiority, P > .1 for superiority). The median progression-free survival was 16 versus 12 months (HR = 0.73; P = < 0.01 for noninferiority, P < .01 for superiority). Toxicities were similar, except that more patients in the PC arm had hematologic toxicity and more patients in the PI arm had confusion and genitourinary hemorrhage. Among 90 eligible patients with OCS, those in the PC arm had longer OS (30 v 25 months) and progression-free survival (15 v 10 months) than those in the PI arm, but with limited precision, these differences were not statistically significant.

PC was not inferior to the active regimen PI and should be standard treatment for UCS.

Please see the National Institute of Health’s ClinicalTrials.gov site for more information.

NCT04149275 is a single site Investigator-Initiated Trial at UAB, funded by BMS and Exelixis. It is tailored specifically for recurrent carcinosarcoma patients, using the combination of immunotherapy with anti-angiogenic therapy. This trial combines Cabozantinib, an oral medication that limits tumor growth by targeting VEGF2 and c-MET, with Nivolumab (anti-PD1, trade name=Opdivo) and Ipilimumab (anti-CTLA4, trade name=Keytruda) infusions, which are both immunotherapy agents that have shown more promise working together in gynecologic cancer than either agent alone.

Rebecca Arend, MD, is the Principal Investigator (PI) for this study. For Dr. Arend’s contact information, click here.

Please see the National Institute of Health’s ClinicalTrials.gov site for more information.

NCT03395080 is a multi-site study, currently open at 17 sites in the US (see locations below) and funded by Leap Therapeutics. Dr. Arend is the National Principal Investigator (PI) of the trial.  This trial initially was open to endometrial cancer and ovarian cancer patients and carcinosarcoma patients with a Wnt mutation. Due to some successful responses seen in the carcinosarcoma patients, two additional arms have been opened specific for patients with carcinosarcoma (uterine or ovarian).

The study is utilizing a Wnt modulator, DKN-01 (anti-DKK1), as a monotherapy (that is, this drug alone) or in combination with paclitaxel (trade name=Taxol).

For Dr. Arend’s contact information, click here.

Please see the National Institute of Health’s ClinicalTrials.gov site for more information.

Locations of this multi-site clinical trial: [alphabetically by state and with Principal Investigator noted]

• The University of Alabama, Birmingham, AL: Rebecca Arend, MD (PI)
• HonorHealth, Scottsdale, AZ: Jasgit Sachdev, MD
• Florida Cancer Specialists & Research Institute, West Palm Beach, FL: Howard Goodman, MD
• University of Chicago, Chicago, IL: S. Diane Yamada, MD
• Massachusetts General Hospital, Boston, MA: Cesar Castro, MD
• Dana Farber Cancer Institute, Boston, MA: Ursula Matulonis, MD
• HCA Midwest Health System Clinical Research, Kansas City, MO: Kristopher LyBarger, MD
• Cleveland Clinic, Cleveland, OH: Haider Mahdi, MD
• Ohio State University Wexner Medical Center, Hilliard, OH: David O’Malley, MD
• Stephenson Cancer Center, Univ of Oklahoma, Oklahoma City, OK: Camille Gunderson, MD
• The University of Tennessee West Cancer Center, Germantown, TN: Adam ELNaggar, MD
• Tennessee Oncology, PLLC, Nashville, TN: Erika P Hamilton, MD
• Vanderbilt University Medical Center, Nashville, TN: Marta A Crispens, MD
• University of Texas Southwestern Medical Center, Dallas, TX: David Miller, MD
• University of Virginia Cancer Center, Charlottesville, VA: Linda Duska, MD
• University of Wisconsin, Madison, WI: Lisa Barroilhet, MDFroedtert and the Medical College of Wisconsin, Milwaukee, WI: William Bradley, MD