Ignite Creation Date:
2025-12-25 @ 2:49 AM
Ignite Modification Date:
2025-12-26 @ 1:31 AM
Study NCT ID:
NCT06180733
Status:
RECRUITING
Last Update Posted:
2023-12-22
First Post:
2023-12-04
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Neo-adjuvant Pembrolizumab as an Alternative Treatment for MMRd Uterine Cancer
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D016889', 'term': 'Endometrial Neoplasms'}, {'id': 'D014594', 'term': 'Uterine Neoplasms'}, {'id': 'D008224', 'term': 'Lymphoma, Follicular'}], 'ancestors': [{'id': 'D005833', 'term': 'Genital Neoplasms, Female'}, {'id': 'D014565', 'term': 'Urogenital Neoplasms'}, {'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D014591', 'term': 'Uterine Diseases'}, {'id': 'D005831', 'term': 'Genital Diseases, Female'}, {'id': 'D052776', 'term': 'Female Urogenital Diseases'}, {'id': 'D005261', 'term': 'Female Urogenital Diseases and Pregnancy Complications'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D000091662', 'term': 'Genital Diseases'}, {'id': 'D008228', 'term': 'Lymphoma, Non-Hodgkin'}, {'id': 'D008223', 'term': 'Lymphoma'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D008232', 'term': 'Lymphoproliferative Disorders'}, {'id': 'D008206', 'term': 'Lymphatic Diseases'}, {'id': 'D006425', 'term': 'Hemic and Lymphatic Diseases'}, {'id': 'D007160', 'term': 'Immunoproliferative Disorders'}, {'id': 'D007154', 'term': 'Immune System Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C582435', 'term': 'pembrolizumab'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 12}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2023-12-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2023-12', 'completionDateStruct': {'date': '2028-01', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2023-12-12', 'studyFirstSubmitDate': '2023-12-04', 'studyFirstSubmitQcDate': '2023-12-12', 'lastUpdatePostDateStruct': {'date': '2023-12-22', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2023-12-22', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2027-12-30', 'type': 'ESTIMATED'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'The nature of the immune responses during treatment.', 'timeFrame': 'Will be determined after study completion, an average of 1 year'}, {'measure': 'The involvement of TDLN in the immune responses on-treatment', 'timeFrame': 'Will be determined after study completion, an average of 1 year'}, {'measure': 'Changes in circulating tumour DNA (ctDNA) during treatment', 'timeFrame': 'Will be determined after study completion, an average of 1 year'}, {'measure': 'Pipelle biopsy as a predictor for response', 'timeFrame': 'Will be determined after study completion, an average of 1 year'}], 'primaryOutcomes': [{'measure': 'Establish fraction of patients that achieve major pathologic response', 'timeFrame': 'Tumor tissue is collected during standard of care hysterectomy (6 months after baseline)', 'description': 'The primary objective of this phase 2 trial is to establish the fraction of patients that achieve a major pathologic response (MPR) after 9 cycles of pembrolizumab, with the ultimate aim of informing a follow-up randomized trial. MPR was chosen as primary endpoint to align with ongoing randomized phase 3 ICB trials on neo-adjuvant vs. adjuvant treatment in other tumor types (e.g. the NADINA trial in melanoma; NCT04949113).'}], 'secondaryOutcomes': [{'measure': 'Radiologic response', 'timeFrame': 'MRI is scheduled before start study drug (week 4), during treatment (week 11, 17, and 23) and before surgery (week 32)', 'description': 'To establish the objective response rate by radiologic assessment using MRI and RECIST1.1.'}, {'measure': 'Recurrence Free Survival', 'timeFrame': 'RFS will be assessed 2 years after baseline', 'description': 'To establish recurrence free survival (RFS) defined as the number of patients alive without any progress or recurrence at 2 years from disease diagnosis'}, {'measure': 'Safety and tolerability (Adverse Events)', 'timeFrame': 'Through study completion, an average of 6 months per patient', 'description': 'Adverse events will be documented according CTCAE'}]}, 'oversightModule': {'isUsExport': True, 'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Endometrial Cancer', 'Uterine Cancer', 'MMRd', 'Grade 3', 'Clear Cell', 'Neo-adjuvant', 'Pembrolizumab'], 'conditions': ['Endometrial Cancer']}, 'descriptionModule': {'briefSummary': 'The goal of this clinical trial is to establish the fraction of patients that achieve a major pathological response (MPR) after 9 cycles of pembrolizumab, with the ultimate aim of informing a follow-up randomized trial.\n\nParticipants will receive 9 cycles of pembrolizumab before their standard of care hysterectomy.', 'detailedDescription': 'Objective: Based on the success of the pilot feasibility study, we propose a phase 2 trial to establish the fraction of patients that achieve a major pathologic response (MPR) after 9 cycles of pembrolizumab, with the ultimate aim of informing a follow-up randomized trial. MPR was chosen as primary endpoint to align with ongoing randomized phase 3 ICB trials on neo-adjuvant vs. adjuvant treatment in other tumor types (e.g. the NADINA trial in melanoma; NCT04949113).\n\nStudy design: Patients will be treated with neo-adjuvant pembrolizumab (200mg IV Q3W, for a total of 9 administrations), followed by SoC surgery and adjuvant therapy where indicated. Tumor responses to pembrolizumab will be assessed by a pathologist (primary endpoint) using material from the SoC surgery. In addition, tumor response will be evaluated by MRI (secondary endpoint) after the second, fourth, sixth, and last cycle of pembrolizumab. In case of suspicion of progressive disease, the hysterectomy will immediately take place. Peripheral blood and tumor samples will be used to explore dynamics of tumor and immune responses during therapy.\n\nFollow-up: Adverse events will be followed up to 6 months after the final pembrolizumab administration. Outside the study protocol patients will be followed-up according SoC guidelines for uterine cancer. Patients will be asked to participate in follow-up of disease progression (2-year recurrence-free survival).\n\nStudy population: Primary MMRd UC patients at high-risk of recurrence (endometrioid grade 3 or clear cell histology) who are intended to be treated with a hysterectomy.\n\nIntervention: Pembrolizumab, 200mg IV Q3W for a total of 9 administrations per patient, prior to SoC therapy.'}, 'eligibilityModule': {'sex': 'FEMALE', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n* Female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed primary diagnosis of G3/CC MMRd uterine cancer who are intended to be treated with hysterectomy.\n* A female participant is eligible to participate if she is not pregnant, not breastfeeding, is not a woman of childbearing potential (WOCBP) or agrees to follow contraceptive guidance during the treatment period and at least until standard-of-care hysterectomy.\n* The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.\n\nExclusion Criteria:\n\n* A WOCBP who has a positive serum pregnancy test at screening.\n* Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).\n* Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks \\[could consider shorter interval for kinase inhibitors or other short half-life drugs\\] prior to allocation.\n* Has received prior radiotherapy within 2 weeks of start of study treatment or radiation-related toxicities requiring corticosteroids. Note: Two weeks or fewer of palliative radiotherapy for non-CNS disease with a 1-week washout is permitted.\n* Has received a live vaccine or live-attenuated vaccine within 30 days before to the first dose of study intervention. Administration of killed vaccines and Covid vaccines is allowed.\n* Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.\n* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.\n* Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.\n* Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.\n* Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.\n* Has active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid).\n* Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.\n* Has an active infection requiring systemic therapy.\n* Has a known history of Human Immunodeficiency Virus (HIV). Note: No HIV testing is required unless mandated by local health authority.\n* Has a known history of Hepatitis B (defined as Hepatitis B surface antigen \\[HBsAg\\] reactive) or known active Hepatitis C virus (defined as HCV RNA \\[qualitative\\] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.\n* Has not adequately recovered from major surgery or has ongoing surgical complications.\n* Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.\n* Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.\n* Is pregnant or breastfeeding, or expecting to conceive within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment."}, 'identificationModule': {'nctId': 'NCT06180733', 'acronym': 'PAM-II', 'briefTitle': 'Neo-adjuvant Pembrolizumab as an Alternative Treatment for MMRd Uterine Cancer', 'organization': {'class': 'OTHER', 'fullName': 'University Medical Center Groningen'}, 'officialTitle': 'Neo-adjuvant Pembrolizumab as an Alternative Treatment for MMRd Uterine Cancer, a Phase II Efficacy Study', 'orgStudyIdInfo': {'id': 'PAM-UMCG-002'}, 'secondaryIdInfos': [{'id': '2022-003922-27', 'type': 'EUDRACT_NUMBER'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Primary MMRd endometrial cancer patients', 'interventionNames': ['Drug: Pembrolizumab Injection [Keytruda]']}], 'interventions': [{'name': 'Pembrolizumab Injection [Keytruda]', 'type': 'DRUG', 'description': 'Pembrolizumab (Keytruda), 200mg IV Q3W for a total of 9 administrations per patient, prior to standard-of-care surgery. Patients will be monitored for response and possible progression using MRI and pipelle biopsies.', 'armGroupLabels': ['Primary MMRd endometrial cancer patients']}]}, 'contactsLocationsModule': {'locations': [{'zip': '9700 RB', 'city': 'Groningen', 'status': 'RECRUITING', 'country': 'Netherlands', 'contacts': [{'name': 'Koen Brummel, Drs.', 'role': 'CONTACT', 'email': 'k.brummel@umcg.nl', 'phone': '+31625649882'}, {'name': 'Anneke L Eerkens, Drs.', 'role': 'CONTACT', 'email': 'a.l.eerkens@umcg.nl'}, {'name': 'Hans W Nijman, Prof. dr.', 'role': 'PRINCIPAL_INVESTIGATOR'}, {'name': 'Mathilde Jalving, Dr.', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'University Medical Centre Groningen', 'geoPoint': {'lat': 53.21917, 'lon': 6.56667}}], 'centralContacts': [{'name': 'Koen Brummel, Drs.', 'role': 'CONTACT', 'email': 'k.brummel@umcg.nl', 'phone': '+31625649882'}, {'name': 'Anneke L Eerkens, Drs.', 'role': 'CONTACT', 'email': 'a.l.eerkens@umcg.nl'}], 'overallOfficials': [{'name': 'Hans W Nijman, Prof. dr.', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University Medical Center Groningen, UMCG'}, {'name': 'Mathilde Jalving, Dr.', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University Medical Center Groningen, UMCG'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University Medical Center Groningen', 'class': 'OTHER'}, 'collaborators': [{'name': 'Merck Sharp & Dohme LLC', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Head of Obstetrics and Gynecology, Prinicpal Investigator', 'investigatorFullName': 'Hans W. Nijman, MD PHD', 'investigatorAffiliation': 'University Medical Center Groningen'}}}}