Neoplasms

All Conditions

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Recurrence

Carcinosarcoma

Mixed Tumor, Mullerian

Endometrial Neoplasms

Adenoma, Pleomorphic

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Sarcoma

Neoplasms, Connective and Soft Tissue

Malignant Mixed Mullerian Tumor

Soft Tissue Sarcoma

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Durvalumab

Immunoglobulins

Tremelimumab

Antineoplastic Agents, Immunological

Patients will receive intravenous infusion of durvalumab 1500mg Fixed Dose every 4 weeks until patient develops a loss of clinical benefit or experiences unacceptable toxicities.

Patients will receive 1500mg Flat Dose durvalubmab via intravenous infusion every 4 weeks for up to 4 cycles and 75mg tremelimumab via intravenous infusion every 4 weeks for up to 4 cycles, and then continue 1500mg Fixed Dose durvalumab every 4 weeks until patient develops a loss of clinical benefit or experiences unacceptable toxicities.

Vicky Makker, MD

This study will test the safety and efficacy of the experimental drug called durvalumab with or without another experimental drug called tremelimumab in endometrial cancer.

Radiologic tumor assessment will be repeated every 8 weeks +/- 7 days for the first 48 weeks and then every 12 weeks +/- 7 days until PD. For patients who remain progression free 2 years post completion of protocol directed treatment, every 6 months +/- 1 month. irRECIST assessments will only be completed for patients continuing treatment beyond PD.

A Study of Durvalumab With or Without Tremelimumab in Endometrial Cancer

A Phase 2 Trial of Durvalumab [MEDI4736](Anti-PD-L1 Antibody) With or Without Tremelimumab (Anti-CTLA-4 Antibody) in Patients With Persistent or Recurrent Endometrial Carcinoma and Endometrial Carcinosarcoma

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Memorial Sloan Kettering Cancer Center

Patients will receive intravenous infusion of durvalumab 1500mg Fixed Dose every 4 weeks until patient develops a loss of clinical benefit or experiences unacceptable toxicities.

Durvalumab

Durvalubmab

Patients will receive 1500mg Flat Dose durvalubmab via intravenous infusion every 4 weeks for up to 4 cycles and 75mg tremelimumab via intravenous infusion every 4 weeks for up to 4 cycles, and then continue 1500mg Fixed Dose durvalumab every 4 weeks until patient develops a loss of clinical benefit or experiences unacceptable toxicities.

Durvalumab

Tremelimumab

Durvalubmab + Tremelimumab

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Vicky Makker, MD

Treatment Efficacy Determined by Measuring the Overall Response Rate

Overall Study

Gland and Hormone Related Diseases

Ovarian Neoplasms

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Endocrine System Diseases

Gonadal Disorders

Ovarian Carcinosarcoma

Ovarian Cancer

Gemcitabine

Paclitaxel

Albumin-Bound Paclitaxel

Doxorubicin

Liposomal doxorubicin

Niraparib

Topotecan

Dostarlimab

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Niraparib, 200 mg or 300 mg, daily dose

TSR042, intravenous infusion on Day 1 of every 21-day cycle at 500 mg for the 4 first cycles, followed by 1,000 mg on Day 1 of every 42-day cycle thereafter

Chemotherapies (Standard of care)

For Ovarian Cancer Patients Paclitaxel, 80 mg/m², Intravenous, Day 1, 8, 15 every 28 days Pegylated Liposomal Doxorubicin, 40 mg/m², Intravenous, every 28 days Topotecan, 4mg/m², Intravenous, Day 1, 8, 15 every 28 days

For Endometrial Cancer Patients Doxorubicin, 60 mg/m², Intravenous, every 21 days Paclitaxel, 80 mg/m², Intravenous, Day 1, 8, 15 every 28 days Gemcitabine, 800 mg/m², Intravenous, Day 1, 8 every 21 days

Combination of 2 drugs, a PARP Inhibitor and an Anti-PD-1

Niraparib + TSR-042 (Dostarlimab)

Chemotherapy Drugs

Carcinosarcomas (CS) (malignant mixed Müllerian tumors) are highly aggressive and rare tumors with a worldwide annual incidence between 0.5-3.3 cases/100.000 women. Gynecological CS, i.e. ovarian CS (OCS) and uterine CS (UCS), have a 5-year overall survival (OS) \< 10% and a poor prognosis. After initial treatment (surgery +/- adjuvant radiotherapies +/- chemotherapies (CT)), vast majority of patients relapsed and received diverse CT producing modest benefits, and nearly all patients will die. After first line CT including platinum salt, monotherapy (doxorubicin or paclitaxel) is frequently used for relapsed patients, but the response rate (RR) is \<20%, progression-free survival (PFS) \<4 months, and OS \<1 year. In this unmet need situation, a better knowledge of these aggressive neoplasms is essential to propose new therapeutic options.

Phase 2 :

Arm A - Niraparib

Arm B - Niraparib plus TSR-042

Arm C - Chemotherapy drugs

Peak the winner between the Arm A or the arm B

Phase 3:

Arm A: The best arm of the phase 2

Arm B: Chemotherapy drugs

Recurrent Ovarian CarcinoSarcoma Anti-pd-1 Niraparib

A Multicentric Randomized Phase II/III Evaluating TSR-042 (Anti-PD-1 mAb) in Combination With Niraparib (Parpi) Versus Niraparib Alone Compared to Chemotherapy in the Treatment of Metastatic or Recurrent Endometrial or Ovarian Carcinosarcoma After at Least One Line of Chemotherapy

RR is defined as the proportion of patients with a partial response or complete response 4 months after randomization

OS is the time from the date of the randomization until death due to any cause

PFS is the time from randomization to the date of event defined as the first documented progression (RECIST 1.1) or death due to any cause.

TTST is the time from the date of randomization to the earliest date of anti-cancer therapy start following study treatment discontinuation, or death by any cause in the absence of start of new anti-cancer therapy

PFS2 is the time from the date of randomization to the second objective disease progression, or death from any cause, whichever occurs first.

ORR is the proportion of patients with a best response of Complete Response or Partial Response.

Assessed with questionnaires to be completed by patient and collected frequently during the study

Tesaro, Inc.

ARCAGY/ GINECO GROUP

Adenocarcinoma

Neoplasm Metastasis

Carcinoma, Ovarian Epithelial

Cystadenocarcinoma, Serous

Adenocarcinoma, Clear Cell

Fallopian Tube Neoplasms

Cystadenocarcinoma

Carcinoma, Endometrioid

Fallopian Tube Diseases

Neoplasms, Cystic, Mucinous, and Serous

Ovarian Epithelial Cancer

Fallopian Tube Cancer

Adenocarcinoma of the Appendix

Micronutrients

Hematinics

Vitamins

Folic Acid

Vitamin B Complex

Exatecan

Folinic Acid

Folate

Vitamin B9

Dose Escalation: Escalating doses of ELU001 Dose Expansion: Recommended Dose for Expansion (or RP2D)

Folic-acid functionalized C'Dot-Drug-Conjugate (FA-CDC)

ELU001

Clinical Trial Operations

David J Park, MD

Gerardo Colon-Otero, MD

Colon-Otero Gerardo, M

David J Kahn, MD

Cesar A Perez Batista, MD

Srilata Gundala, MD

Michelle R Rowland, MD, Phd, MPH

Andrea Wahner-Hendrickson, MD

Clinical Trials Information

Yonina R Murciano-Goroff, MD, MsC

Carey Anders, MD

Wen Wee Ma, MBBS

Babar Bashir, MD

Babir Bashir, MD

Cara Mathews, MD

Luis Rojas-Espaillat, MD

Erika P Hamilton, MD

Karina Amaro, Study Coord

Teresa Marquez, ClinTrialMg

Douglas Orr, MD

NEXT Coordinators

Anthony W Tolcher, MD, FRCPC

Elizabeth Swisher, MD

Eliel Bayever, MBBCh, MRCP

This study, ELU- FRα-1, is focused on adult subjects who have advanced, recurrent or refractory folate receptor alpha (FRα) overexpressing tumors considered to be topoisomerase 1 inhibitor-sensitive based on scientific literature, and, in the opinion of the Investigator, have no other meaningful life-prolonging therapy options available.

ELU001 is a new chemical entity described as a C'Dot drug conjugate (CDC), consisting of payloads (exatecans) and targeting moieties (folic acid analogs) covalently bound by linkers to the C'Dot particle carrier. ELU001 will be the first drug-conjugate of its kind to be introduced into the clinic, a first in class, and a novel molecular entity.

The study has two parts: Part 1 Dose Escalation Safety Study to identify the maximum tolerated dose (MTD) and/or the recommended phase 2 dose (RP2D), and Part 2 Tumor Group Expansion Cohort(s) where specific cancer types will be evaluated for efficacy and safety at the RP2D.

Part 1, subjects with cancer types with a high likelihood of having FRα overexpressing tumors based on historical data, specifically, ovarian, endometrial, colorectal, gastric, gastroesophageal junction, triple negative breast, or non-small cell lung cancers, or cholangiocarcinoma, will be enrolled in a basket clinical study. Retrospective analysis of folate receptor alpha (FRα) expression status will be determined. Part 1 is currently closed for further recruitment.

Part 2 Stage 1 of a Simon's Two-Stage design, tumor group expansion cohorts, each consisting of subjects with cancer types studied as part of the basket in Part 1. Part 2 is open for recruitment.

Dose Escalation Dose Expansion, Simon's 2-stage

A Study to Evaluate ELU001 in Patients With Solid Tumors That Overexpress Folate Receptor Alpha (FRα)

Dose Escalation and Expansion Clinical Study to Evaluate the Safety and Efficacy of ELU001 in Subjects Who Have Advanced, Recurrent or Refractory FRα Overexpressing Tumors

To determine the MTD and/or RP2D of ELU001 in patients with over-expressing Folate Receptor Alpha tumors. When at least 2 out of 6 patients in a given dose-level experience a dose-limiting toxicity (DLT), the dose is considered to have exceeded the MTD. The MTD, therefore, is defined as the previous highest tested dose of ELU001 that did not cause a DLT in the first cycle of treatment. In the event of emerging data during Part 1, the Sponsor may, in consultation with a dose-level safety review group, decide to define a recommended dose for expansion (in for Part 2) (RP2D) instead of the MTD. DLTs are defined as a treatment-emergent adverse event (TEAE) or abnormal laboratory value related to ELU001 treatment that result in a failure to meet the criteria for re-treatment.

Percentage of Participants with confirmed objective response as assessed by the investigator and per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 CR is defined as the disappearance of all target or non-target lesions. PR is defined as at least 30 percent (%) decrease in the sum of the longest diameters (SoD) of target lesions, taking as reference the baseline SoD.

Time Measurement: DOR will begin at the date that a response has been identified (stable disease, partial response, or complete response) until the date of progressive disease (PD). PD is defined of at least a 20% increase in the sum of the longest diameters of the target lesions from data of initial response.

The number of participants Frequency/severity of abnormalities in vital signs measurements, physical examination findings, changes in clinical laboratory parameters, and incidence of adverse events after taking ELU001.

Elucida Oncology

Pembrolizumab

Olaparib

Immune Checkpoint Inhibitors

Eligible patients will receive olaparib in combination with pembrolizumab. Olaparib will be administered orally at 300 mg every 12 hours. Pembrolizumab will be administered intravenously (IV) at 200mg every 3 weeks.

Pembrolizumab will be administered intravenously (IV) at 200mg every 3 weeks.

Olaparib will be administered orally at 300 mg every 12 hours.

Maria Rubinstein, MD

The purpose of this study is to find out whether the combination of pembrolizumab and olaparib is an effective treatment for people with persistent or recurrent endometrial cancer or endometrial carcinosarcoma. The researchers will also look at the safety of the drug combination and whether it causes few or mild side effects in participants.

This is a prospective, single arm, open-label, single-institution phase II trial.

A Study of Pembrolizumab and Olaparib in People With Endometrial Cancer or Endometrial Carcinosarcoma

A Phase II Trial of Pembrolizumab Plus Olaparib for the Treatment of Patients With Persistent/Recurrent Endometrial Cancers

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Merck Sharp & Dohme LLC

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Durvalumab With or Without Tremelimumab in Endometrial Cancer	NCT03015129	Endometrial Can... Endometrial Car... Endometrial Car... Endometrial Can... Endometrial Car...	Durvalumab Tremelimumab	18 Years -	Memorial Sloan Kettering Cancer Center
Recurrent Ovarian CarcinoSarcoma Anti-pd-1 Niraparib	NCT03651206	Ovarian Carcino... Endometrial Car...	Niraparib Niraparib + TSR... Chemotherapy Dr...	18 Years -	ARCAGY/ GINECO GROUP
A Study of Durvalumab With or Without Tremelimumab in Endometrial Cancer	NCT03015129	Endometrial Can... Endometrial Car... Endometrial Car... Endometrial Can... Endometrial Car...	Durvalumab Tremelimumab	18 Years -	Memorial Sloan Kettering Cancer Center
Recurrent Ovarian CarcinoSarcoma Anti-pd-1 Niraparib	NCT03651206	Ovarian Carcino... Endometrial Car...	Niraparib Niraparib + TSR... Chemotherapy Dr...	18 Years -	ARCAGY/ GINECO GROUP
A Study to Evaluate ELU001 in Patients With Solid Tumors That Overexpress Folate Receptor Alpha (FRα)	NCT05001282	Ovarian Cancer Ovarian Neoplas... Ovarian Carcino... Endometrial Can... Ovary Cancer Ovary Neoplasm Ovary Disease Ovary Metastasi... Ovarian Disease... Ovarian Cancer ... Ovarian Epithel... Ovarian Adenoca... Ovarian Serous ... Ovarian Neoplas... Ovarian Cancer ... Endometrial Dis... Endometrial Ade... Endometrial Car... Endometrial Cle... Endometrioid Ad... Endometrial Neo... Endometrial Can... Endometrioid Tu... Fallopian Tube ... Peritoneal Canc...	ELU001	18 Years -	Elucida Oncology
A Study of Pembrolizumab and Olaparib in People With Endometrial Cancer or Endometrial Carcinosarcoma	NCT05156268	Endometrial Car...	Pembrolizumab Olaparib	18 Years -	Memorial Sloan Kettering Cancer Center

Spots Global Cancer Trial Database for endometrial carcinosarcoma