Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Adenocarcinoma

Recurrence

Cystadenocarcinoma, Serous

Carcinoma

Cystadenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Cystic, Mucinous, and Serous

Ovarian Cancer

Ovarian Epithelial Cancer

Adenocarcinoma of the Appendix

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Carboplatin

Etoposide

Gemcitabine

Doxorubicin

Liposomal doxorubicin

Albumin-Bound Paclitaxel

Topotecan

Cisplatin

Etoposide phosphate

This is an experimental arm of this study. Allowed therapeutic options:

1. Paclitaxel 60-80 mg/m2 + carboplatin area under curve (AUC) 2-2.7 d 1, 8, 15 every 3 or 4 weeks (Q3W or Q4W);
2. Gemcitabine 1000 mg/m2 d 1, 8 + cisplatin 75 mg/m2 1 every 3 weeks;
3. Doxorubicin 40-50 mg/m2 d 1 + carboplatin AUC5 or cisplatin 60-75 mg/m2 d 1 every 3 weeks;
4. Topotecan 0.75 mg/m2 d 1-3 + cisplatin 60-75 mg/m2 or carboplatin AUC 4-5 d 1 every 3 weeks;
5. Etoposide 100 mg once daily orally d 1-7 + cisplatin 60-75 mg/m2 d1 every 3 weeks.

Up to 6 cycles of chemotherapy will be administered to study participants allocated to this arm.

This is a control arm of this study. Allowed therapeutic options:

1. Paclitaxel 60-80 mg/m2 weekly (or day 1, 8, 15 every 4 weeks schedule);
2. Gemcitabine 1000 mg/m2 d 1, 8, 15 every 4 weeks;
3. Doxorubicin 50-60 mg/m2 d 1 every 3 weeks;
4. Topotecan 1,2-1,5 mg/m2 d 1-5 every 3 weeks;
5. Etoposide 100 mg once daily orally d 1-10 every 3 weeks.

Up to 6 cycles of chemotherapy will be administered to study participants allocated to this arm.

Reintroduction of platinum-based chemotherapy

Platinum-Based Drug

Conventional chemotherapy

Alexey Rumyantsev, MD

This is a phase II/III randomized controlled trial to evaluate efficacy of platinum-based chemotherapy vs conventionally prescribed non-platinum monochemotherapy in patients with platinum-resistant ovarian cancer

Recurrent ovarian cancer (ROC) is usually subdivided to platinum-sensitive (platinum-free interval \[PFI\] ≥6 mo.) and platinum-resistant ovarian cancer \[PROC\] (PFI \<6 mo.) subtypes. Prognosis for the latter group is dismal and current guidelines recommend treating these patients with non-platinum based chemotherapy. However, the evidence behind this is quite unconvincing and according to recent data patients with non-platinum refractory platinum-resistant ovarian cancer could derive benefit from platinum rechallenge. This trial is designed for head-to-head comparison of platinum and non-platinum therapy efficacy in treatment of platinum-resistant ovarian cancer.

Randomized phase II/III trial to assess the efficacy of platinum-based chemotherapy vs standard non-platinum therapy in patients with platinum-resistant recurrent ovarian cancer (ROC)

due to the nature of this disease only female participants are allowed

Efficacy of Platinum-based Chemotherapy in Platinum-resistant Ovarian Cancer) (EPITOC)

Randomized Phase II/III Trial to Assess the Efficacy of Platinum-based Chemotherapy vs Standard Non-platinum Therapy in Patients With Platinum-resistant Recurrent Ovarian Cancer (ROC)

Primary outcome for Phase II part: response rate to treatment according to RECIST1.1 criteria. For patients without measurable disease Rustin criteria is allowed.

Primary outcome for Phase III part: 2. Overall survival defined as time from randomization to death from any reason

Progression-free survival (PFS) defined as time from randomization to disease progression according to RECIST 1.1 criteria or death from any reason;

Overall survival defined as time from randomization to death from any reason (for Phase II part only);

PFS2 defined as time from randomization to second disease progression event according to RECIST 1.1 criteria or death from any reason;

Response rate to treatment according to RECIST1.1 criteria. For patients without measurable disease Rustin criteria is allowed (only for Phase II part).

Blokhin's Russian Cancer Research Center

Uterine Cervical Neoplasms

Vaginal Neoplasms

Vulvar Neoplasms

Uterine Neoplasms

Carcinosarcoma

Mixed Tumor, Mullerian

Adenocarcinoma, Mucinous

Vaginal Cancer

Fallopian Tube Cancer

Malignant Mixed Mullerian Tumor

Vulvar Cancer

Amino Acids

Axitinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Up to 6 doses of INCB099280 administered twice daily (BID) in combination with axitinib BID will be evaluated to identify dose(s) for further evaluation in the dose expansion phase of the study.

On completion of Part 1, participants will be enrolled in 1 of 2 disease-specific cohorts: Cohort 1: Adults with clear-cell gynecological cancers with at least 50% clear-cell histology whose disease progressed on or following at least 1 prior line of systemic chemotherapy and are not candidates for curative surgery or (chemo)radiation. Cohort 2: Adults with rare histological subtype epithelial cancers of the gynecological tract whose disease progressed on or following at least 1 prior line of systemic chemotherapy and are not candidates for curative surgery or (chemo)radiation. One or two doses may be selected from Part 1 for each cohort in the Part 2 Expansion.

Administered as specified in the treatment arm description

INCB099280

axitinib

Incyte Corporation Call Center (ex-US)

Philomena Colucci

This study is being conducted to evaluate the safety and tolerability of INCB099280 in combination with axitinib and to assess the antitumor activity of INCB099280 in combination with axitinib. This study will only be open in the UK and EU.

The study consists of 2 parts. In the Part 1 dose-escalation, participants will be enrolled in up to 6 dose levels of INCB099280 administered in combination with axitinib. In the Part 2 dose expansion, participants will be enrolled into 1 of 2 disease-specific cohorts at the dose(s) identified in Part 1.

A Study of INCB099280 in Combination With Axitinib in Adults With Advanced Solid Tumors

A Phase 1/2 Study of INCB099280 in Combination With Axitinib in Adults With Advanced Solid Tumors

Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. The trial data availability is according to the criteria and process described on https://www.incyte.com/our-company/compliance-and-transparency

Dose-limiting toxicity will be defined as the occurrence of any of the toxicities as per protocol.

Defined as adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug.

Number of participants with TEAEs leading to a dose modification (treatment interruption, dose reduction, and permanent discontinuation of either study drug).

Defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR), as determined by investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

Defined as the best overall response of CR, PR, or stable disease (SD) of at least 11 weeks from the start of treatment by investigator assessment per RECIST v1.1.

Defined as the time from the first CR or PR until disease progression by investigator assessment per RECIST v1.1 or death from any cause, whichever occurs earlier.

PK parameters will be calculated from the blood plasma concentrations of INCB099280 and axitinib using standard noncompartmental (model independent) PK methods.

Incyte Corporation

Endometrial Neoplasms

Uterine Diseases

Niraparib

Poly(ADP-ribose) Polymerase Inhibitors

Single arm. Following the initial assessment and endometrial biopsy the participants will receive niraparib for 28 days. After the treatment period the patients will be surgically staged. All participants will receive the standard of care.

Low dose oral niraparib capsules (2 x 100 mg) once a day for 28 days

Niraparib oral capsule

Shannon Salvador, MD MSc

David Knigin, MD PhD

Walter Gotlieb, MD PhD

The study will investigate the effect of niraparib on tumor tissue in chemotherapy naïve, newly diagnosed, high-grade endometrial cancer patients. Biomarkers of cognate molecular pathways as well as investigational assays will be used to study the antineoplastic effect of the drug.

Niraparib is a FDA approved Poly(ADP-ribose) polymerase inhibitor (PARPi) for the treatment of platinum-sensitive ovarian serous carcinoma. The safety profile of niraparib was established in phase III clinical trials. The therapeutic effect of niraparib on serous endometrial carcinoma is now being investigated in several clinical trials. However, the antineoplastic effect and the safety profile of niraparib in chemotherapy naïve high-grade endometrial cancer patients is unknown. By employing a phase 0 exploratory trial design, the investigators will study the niraparib's effect on endometrial cancer in chemotherapy naïve patients using molecular biomarkers as sentinels for the antineoplastic effect. Women diagnosed by endometrial biopsy with high-grade endometrial cancer will receive niraparib for 28 days. Staging surgery will be performed 4-6 weeks after the diagnosis (standard of care). The investigators will use the pre-operative biopsy and the surgical specimen to perform comparative multidimensional analysis of endometrial tumors before and after exposure to niraparib.

Niraparib in High-grade Endometrial Cancer Trial

The Molecular and the Clinical Effects of Preoperative Niraparib in Patients With High-grade Endometrial Cancer: Phase 0 Exploratory Trial

Gene expression profile by RNA sequencing extracted from snap-frozen tumor tissue. Unsupervised hierarchical clustering of 2-fold changed genes will be used to detect the pathways affected by niraparib treatment.

Mutational signature and the altered genes of the DNA repair pathway will be identified by DNA next generation sequencing. Genomic findings will be correlated with molecular analysis for discovery of biomarkers for niraparib sensitivity in chemotherapy-naïve endometrial cells.

Cancer cell proliferation will be quantitatively assessed using immunohistochemical staining for cell-cycle proteins.

Ki-67 (MIB) stains nuclei of cells in G1-S-G2 phases of the cell-cycle. The proliferation index will be calculated as percent of tumor positive cells. The primary outcome fold change in proliferation index after exposure to niraparib. The quantification will be done by image analysis software with pathologist supervision.

The levels of different cell-cycle related proteins increase and decrease throughout the cell cycle, each having its own expression pattern.

Tumor specimens will be stained for Cyclin D1, Geminin and p21 proteins. The proportion of positive nuclei of each marker after exposure to niraparib will be estimated. The results will be integrated to study the effect of niraparib on endometrial cancer cells proliferation.

Cleaved caspase-3 (cCas-3) marks cells that activated the programmed cell-death process. cCas-3 positive tumor cells will be compared before and after the exposure to niraparib.

Comparison of the thickness of endometrial lining before and after treatment

Investigation of the effect of preoperative niraparib on CA125 levels in patients with high grade endometrial carcinoma

Assessment of adverse effects of niraparib in chemotherapy naïve patients according to CTCAE 5.0

Patients' well being will be assessed by a validated questionnaire: Functional Assessment of Cancer Therapy - General (FACT-G). https://www.facit.org

Patients' well being will be assessed by a validated questionnaire: Functional Assessment of Cancer Therapy - Endometrial (FACT-en). https://www.facit.org

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Efficacy of Platinum-based Chemotherapy in Platinum-resistant Ovarian Cancer) (EPITOC)	NCT04055038	Ovarian Cancer Ovarian Neoplas... Serous Adenocar... BRCA1 Mutation BRCA2 Mutation Chemotherapy	Platinum-Based ... Conventional ch...	18 Years - 70 Years	Blokhin's Russian Cancer Research Center
A Study of INCB099280 in Combination With Axitinib in Adults With Advanced Solid Tumors	NCT05949632	Advanced Solid ...	INCB099280 axitinib	18 Years -	Incyte Corporation
Efficacy of Platinum-based Chemotherapy in Platinum-resistant Ovarian Cancer) (EPITOC)	NCT04055038	Ovarian Cancer Ovarian Neoplas... Serous Adenocar... BRCA1 Mutation BRCA2 Mutation Chemotherapy	Platinum-Based ... Conventional ch...	18 Years - 70 Years	Blokhin's Russian Cancer Research Center
Efficacy of Platinum-based Chemotherapy in Platinum-resistant Ovarian Cancer) (EPITOC)	NCT04055038	Ovarian Cancer Ovarian Neoplas... Serous Adenocar... BRCA1 Mutation BRCA2 Mutation Chemotherapy	Platinum-Based ... Conventional ch...	18 Years - 70 Years	Blokhin's Russian Cancer Research Center
Niraparib in High-grade Endometrial Cancer Trial	NCT05289648	Endometrial Can... Serous Adenocar... Uterine Neoplas...	Niraparib oral ...	18 Years -	Sir Mortimer B. Davis - Jewish General Hospital

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