A Phase 1 Clinical Study of NXP800 in Subjects With Advanced Cancers and Expansion in Subjects With Ovarian Cancer

Ovarian Cancer Clinical Trial

Official title:

A Phase 1 Clinical Study of NXP800 in Subjects With Advanced Cancers and Expansion in Subjects With Ovarian Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05226507
• Other study ID #: NXP800-101
• Secondary ID: ENGOT-GYN5/NCRI/
• Status: Recruiting
• Phase: Phase 1
• Start date: December 31, 2021
• Est. completion date: June 2025

Study information

• Verified date: May 2024
• Source: Nuvectis Pharma, Inc.
• Contact: Diane Marsolini
• Phone: 201 627-8154
• Email: dmarsolini[@]nuvectis.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the dose escalation phase is to evaluate the safety profile of escalating doses and dose schedules of NXP800. In the expansion phase the preliminary efficacy in subjects with ARID1a mutated ovarian clear cell and ovarian endometrioid cancers will be estimated.

Description:

Part A of the study is a dose escalation by cohort study of NXP800 administered to patients with advanced cancers. The study will identify the maximum tolerated dose (MTD) and propose dose and dose schedules for future studies.

In Part B doses selected in Part A are administered to patients with platinum-resistant, ARID1a-mutated ovarian carcinoma.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 61
• Est. completion date: June 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Part A Inclusion Criteria:

• Provide written informed consent.

• 18 years old or older.

• Life expectancy of at least 12 weeks.

• Histologically- or cytologically-confirmed, advanced, metastatic, and/or progressive solid tumors for whom there is no authorized or effective therapy available, or for whom such therapies are considered inappropriate by the Investigator (in Part B, subjects with specific cancer types will be enrolled; Specific criteria will be introduced in a protocol amendment).

• Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.

• Eastern Cooperative Oncology Group (ECOG) performance status of = 2.

Part A Exclusion Criteria:

• Radiotherapy (except for palliative reasons), endocrine therapy, chemotherapy, or investigational agent within 28 days, (42 days for nitrosoureas, mitomycin-C) of first dose of NXP800. Subjects can continue to receive bisphosphonates due to metastatic bone disease or GnRH agonists if they have prostate cancer.

• Ongoing toxic manifestations of previous treatments > Grade 2.

• Subjects with treated brain metastases are eligible if there is no evidence of progression for at least 28 days after central nervous system (CNS) directed treatment, as ascertained by clinical examination and brain imaging (magnetic resonance imaging [MRI] or computed tomography [CT] scan) during the Screening period.

• Female subjects who can become pregnant (or are already pregnant or lactating).

• Male subjects with partners of childbearing potential (unless they agree to take measures not to father children by using a barrier method of contraception (condom plus spermicide) or to sexual abstinence).

Part B Inclusion Criteria:

• Provide written informed consent.

• 18 years old or older.

• Subjects with the following ARID1a mutated, ovarian/fallopian tube/primary peritoneal cancer histologies (ARID1a mutation status determined by a DNA-based Next Generation Sequencing test):

• Clear cell ovarian carcinoma (= 50% clear cell carcinoma with no serous differentiation)

• Endometrioid ovarian carcinoma

• Subjects must have disease progression within 6 months (182 days) from completion of platinum-based therapy (6 months should be calculated from the date of the last administered dose of platinum therapy to the date of radiographic imaging showing progression)

• Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.

• Subjects with a BRCA mutation must have received prior treatment with a PARP inhibitor.

• Subjects must have received at least 1 but not more than 3 prior systemic lines of anticancer therapy, including at least 1 line of therapy containing bevacizumab.

• Adjuvant + neoadjuvant are considered one line of therapy

• Maintenance therapy (i.e., bevacizumab, PARP inhibitors) will be considered as part of the preceeding line of therapy and are not counted independently.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

• Subjects must have a sufficient archival Formalin-Fixed Paraffin-Embedded (FFPE) tissue specimen, or be willing to consent to a fresh tissue biopsy during the study.

Part B Exclusion Criteria:

• Subjects with disease that did not respond to, or has progressed during or within 4 weeks of the last dose of first-line platinum containing chemotherapy.

• Radiotherapy (except for palliative reasons), endocrine therapy, chemotherapy, or investigational agent within 28 days, (42 days for nitrosoureas, mitomycin-C) of first dose of NXP800.

• Ongoing toxic manifestations of previous treatments > Grade 2, with the exception of alopecia.

• Subjects with treated brain metastases are eligible if there is no evidence of progression for at least 12 weeks while off corticosteroids after central nervous system (CNS) directed treatment, as ascertained by clinical examination and brain imaging (magnetic resonance imaging [MRI] or computed tomography [CT] scan) during the Screening period.

• Female subjects who can become pregnant (or are already pregnant or lactating).

Related Conditions & MeSH terms

• Adenocarcinoma
• Advanced Solid Tumor
• ARID1A Gene Mutation
• Carcinoma, Endometrioid
• Carcinoma, Ovarian Epithelial
• Ovarian Cancer
• Ovarian Clear Cell Adenocarcinoma
• Ovarian Clear Cell Carcinoma
• Ovarian Clear Cell Tumor
• Ovarian Endometrioid Adenocarcinoma
• Ovarian Endometrioid Tumor
• Ovarian Neoplasms

Intervention

Drug:
• NXP800
NXP800 is an anti-neoplastic, oral small molecule.

Locations

Country	Name	City	State
United Kingdom	Addenbrookes Hospital	Cambridge
United Kingdom	The Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	Royal Marsden Hospital	London Borough of Sutton	Sutton Surrey
United States	Women's Cancer Care Associates	Albany	New York
United States	University of Colorado Cancer Center	Aurora	Colorado
United States	University of Virginia Health System	Charlottesville	Virginia
United States	The Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Oncology Associates of Oregon	Eugene	Oregon
United States	Texas Oncology	Fort Worth	Texas
United States	University of Iowa	Iowa City	Iowa
United States	UC San Diego Health - Moores Cancer Center	La Jolla	California
United States	Mount Sinai Comprehensive Cancer Center	Miami Beach	Florida
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Yale Gynecologic Oncology	New Haven	Connecticut
United States	OU Health Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	Honor Health	Phoenix	Arizona
United States	VCU Massey Comprehensive Cancer Center	Richmond	Virginia
United States	Oklahoma Cancer Specialists and Research Institute	Tulsa	Oklahoma
United States	Sidney Kimmel Cancer Center, Asplundh Cancer Pavilion	Willow Grove	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
Nuvectis Pharma, Inc.	European Network of Gynaecological Oncological Trial Groups (ENGOT), GOG Foundation

Countries where clinical trial is conducted

United States,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A: Number of patients with treatment related adverse events, clinical laboratory abnormalities, dose limiting toxicities		Day 28
Primary	Part B: Estimates of disease response by RECIST v 1.1		Baseline to 30 days post last dose of NXP800
Primary	Part B: Number of patients with treatment related adverse events, and/or clinical laboratory abnormalities.		Baseline to 30 days post last dose of NXP800
Secondary	Area under the concentration-time curve (AUC) of NXP800		First dose through Day 29
Secondary	Maximum observed concentration (Cmax) of NXP800		First dose through Day 29
Secondary	Time to peak concentration (Tmax) of NXP800		First dose through Day 29
Secondary	Half-life (T1/2) of NXP800		First dose through Day 29