Avelumab in Patients With MSS, MSI-H and POLE-mutated Recurrent or Persistent Endometrial Cancer and of Avelumab/Talazoparib and Avelumab/Axitinib in Patients With MSS Recurrent or Persistent Endometrial Cancer
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ClinicalTrials.gov Identifier: NCT02912572 |
Recruitment Status :
Active, not recruiting
First Posted : September 23, 2016
Last Update Posted : April 19, 2024
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Tracking Information | ||||
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First Submitted Date ICMJE | September 20, 2016 | |||
First Posted Date ICMJE | September 23, 2016 | |||
Last Update Posted Date | April 19, 2024 | |||
Actual Study Start Date ICMJE | November 14, 2016 | |||
Estimated Primary Completion Date | March 2025 (Final data collection date for primary outcome measure) | |||
Current Primary Outcome Measures ICMJE |
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Original Primary Outcome Measures ICMJE |
Activity Of Avelumab In Patients With Recurrent Or Persistent Endometrial Cancer [ Time Frame: 2 years ] As assessed by the frequency of patients who survive progression-free for at least 6 months (PFS6) after initiating therapy or have objective tumor response
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Change History | ||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
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Current Other Pre-specified Outcome Measures | Not Provided | |||
Original Other Pre-specified Outcome Measures | Not Provided | |||
Descriptive Information | ||||
Brief Title ICMJE | Avelumab in Patients With MSS, MSI-H and POLE-mutated Recurrent or Persistent Endometrial Cancer and of Avelumab/Talazoparib and Avelumab/Axitinib in Patients With MSS Recurrent or Persistent Endometrial Cancer | |||
Official Title ICMJE | A Phase 2, Two-Group, Two-Stage, Open-Label Study of Avelumab in Patients With MSS, MSI-H and POLE-mutated Recurrent or Persistent Endometrial Cancer, Avelumab / Talazoparib in Patients With MSS Recurrent or Persistent Endometrial Cancer, and Avelumab / Axitinib in Patients With MSS Recurrent or Persistent Endometrial Cancer | |||
Brief Summary | This research study is evaluating a drug called Avelumab alone and in combination with Talazoparib or Axitinib as a possible treatment for recurrent or metastatic endometrial cancer. | |||
Detailed Description | This research study is a Phase II clinical trial. Phase II clinical trials test the effectiveness of an investigational drug to learn whether the drug works in treating a specific cancer. "Investigational" means that the drug is still being studied and that research doctors are trying to find out more about it-such as the safest dose to use, the side effects it may cause, and if the drug is effective for treating different types of cancer. It also means that the FDA (the U.S. Food and Drug Administration) has not yet approved the drug for use in patients, including people with Metastatic Endometrial Cancer. Avelumab is a drug that may stop cancer cells from growing by enabling the activation of the immune system. Avelumab blocks an immune inhibiting signal that can impair the ability of the immune system to attack cancers. Talazoparib is a drug that stops the activity of a protein (called PARP) that's involved in repairing damage to the DNA within your cells. When PARP is turned off by Talazoparib in cancer cells, DNA damage cannot be repaired and leads to the death of the cancer cells. Axitinib is a drug that may stop cancer cells from growing by blocking certain proteins that cancer cells use to form new blood vessels, which the cancer needs in order to grow. In this research study, the investigators are looking to see whether Avelumab, the combination of Avelumab and Talazoparib, or the combination of Avelumab and Axitinib are effective in treating recurrent and Metastatic Endometrial Cancer. Additionally, the investigators are looking to see if participants whose tumors contain a particular genetic make-up will have better response to Avelumab, the combination of Avelumab and Talazoparib, or the combination of Avelumab and Axitinib. |
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Study Type ICMJE | Interventional | |||
Study Phase ICMJE | Phase 2 | |||
Study Design ICMJE | Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE | Metastatic Endometrial Cancer | |||
Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Konstantinopoulos PA, Gockley AA, Xiong N, Krasner C, Horowitz N, Campos S, Wright AA, Liu JF, Shea M, Yeku O, Castro C, Polak M, Lee EK, Sawyer H, Bowes B, Moroney J, Cheng SC, Tayob N, Bouberhan S, Spriggs D, Penson RT, Fleming GF, Nucci MR, Matulonis UA. Evaluation of Treatment With Talazoparib and Avelumab in Patients With Recurrent Mismatch Repair Proficient Endometrial Cancer. JAMA Oncol. 2022 Sep 1;8(9):1317-1322. doi: 10.1001/jamaoncol.2022.2181. | |||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | ||||
Recruitment Status ICMJE | Active, not recruiting | |||
Actual Enrollment ICMJE |
106 | |||
Original Estimated Enrollment ICMJE |
70 | |||
Estimated Study Completion Date ICMJE | March 2027 | |||
Estimated Primary Completion Date | March 2025 (Final data collection date for primary outcome measure) | |||
Eligibility Criteria ICMJE | Inclusion Criteria: Participants must be classified into one of the following cohorts of recurrent or persistent endometrial cancer of any histology: The MSI/POLE cohort includes endometrial cancers that are: --MSI-H as determined by immunohistochemical complete loss of expression (absence of nuclear immunoreactivity) of at least one of the mismatch repair genes MSH2, MSH6, MLH1 and PMS2. This test is now done routinely for every newly diagnosed endometrial cancer patient in most centers in the US. And/OR: --POLE-mutated, i.e. endometrial cancers known to harbor mutations in the exonuclease domain (amino acid residues 268-471) of polymerase e (POLE) as determined by targeted sequencing or other next generation sequencing assay. Any Clinical Laboratory Improvement Amendments (CLIA)-approved genomic test documenting mutations in the exonuclease domain of POLE gene (amino acid residues 268-471) in the tumor will be accepted as proof of presence of POLE mutations and will lead to classification into this patient cohort. The MSS cohorts include:
Please note: creatinine clearance (CLCR) should be estimated according to the Cockcroft-Gault formula as: CLCR={[(140-age) × weight)]/(72 x SCR)} × 0.85 where CLCR (creatinine clearance) is measured in mL/min, age is expressed in years, weight in kilograms (kg), and SCR (serum creatinine) in mg/dL. NOTE: Patients with moderate renal impairment (defined as an estimated creatinine clearance of 30-59 mL/min) will receive a reduced starting dose of Talazoparib at 0.75 mg PO QD.
Additional inclusion criteria for the avelumab/axitinib cohort:
Exclusion Criteria:
Additional exclusion criteria for the avelumab/axitinib cohort:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | |||
Accepts Healthy Volunteers ICMJE | No | |||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | |||
Listed Location Countries ICMJE | United States | |||
Removed Location Countries | ||||
Administrative Information | ||||
NCT Number ICMJE | NCT02912572 | |||
Other Study ID Numbers ICMJE | 16-322 | |||
Has Data Monitoring Committee | Yes | |||
U.S. FDA-regulated Product | Not Provided | |||
IPD Sharing Statement ICMJE |
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Current Responsible Party | Panagiotis Konstantinopoulos, MD, PhD, Dana-Farber Cancer Institute | |||
Original Responsible Party | Same as current | |||
Current Study Sponsor ICMJE | Dana-Farber Cancer Institute | |||
Original Study Sponsor ICMJE | Same as current | |||
Collaborators ICMJE | Pfizer | |||
Investigators ICMJE |
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PRS Account | Dana-Farber Cancer Institute | |||
Verification Date | April 2024 | |||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |