ACTIVE_NOT_RECRUITING

Tuvusertib Combined With Niraparib or Lartesertib in Participants With Epithelial Ovarian Cancer (DDRiver EOC 302)

Conditions

Ovarian Cancer Ataxia telangiectasia mutated Rad3-related Ataxia telangiectasia mutated Poly-ADP ribose polymerase inhibitor resistance Homologous recombination deficiency

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The purpose of this study is to measure the effect and safety of treatment with tuvusertib combined with either niraparib or lartesertib in participants with epithelial ovarian cancer and to assess any differences between tuvusertib monotherapy and combination therapy. The participants will previously have progressed while treated with a poly ADP ribose polymerase (PARP) inhibitor. The primary objectives of this study are to assess the effect of the treatment in terms of overall response, i.e. whether the tumor disappears, shrinks, remains unchanged, or gets worse and safety in terms of adverse events.

Official Title

An Open-label, Multicenter, Randomized Phase 2 Study of the ATR Inhibitor Tuvusertib in Combination With the PARP Inhibitor Niraparib or the ATM Inhibitor Lartesertib in Participants With BRCA Mutant and/or Homologous Recombination deﬁciency (HRD)-Positive Epithelial Ovarian Cancer That Progressed on Prior PARP Inhibitor Therapy (DDRiver EOC 302)

Quick Facts

Study Start:2024-10-30

Study Completion:2028-01-25

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT06433219

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:FEMALE

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Histologically or cytologically confirmed high grade serous or high grade endometrioid ovarian, primary peritoneal, and/or fallopian tube cancer that is recurrent. * Participants whose tumor carries germline or somatic deleterious or suspected deleterious mutations in the genes BRCA1 (Breast Cancer gene 1) and BRCA2 (Breast Cancer gene 2), and/or tumors with positive HRD status. The presence of any of these mutations and/or the homologous recombination deficiency (HRD) status will be determined according to routinely used local standard of care tests. Results must be available before screening. * Radiologically confirmed/documented disease progression while on Poly (ADP-ribose) polymerase (PARP) inhibitors therapy in either first or second-line maintenance setting (only 1 line of PARPi maintenance is allowed with or without bevacizumab). Note: Documentation of disease progression must be within 28 days of last PARPi dose taken. Surgical salvage intervention and/or focal ablative therapies are allowed, (further disease progression after these interventions must be documented), AND Clinically benefited from PARPi maintenance prior to documented progression, as defined by at least 6 months of treatment duration with no progressive disease observed, AND either, Progression on first-line maintenance PARPi: Participants are allowed maximum 1 additional line of platinum-based chemotherapy before study entry. (note: treatment-free interval on platinum rechallenge must be \>6 months, with documented disease progression prior to study entry). * Intolerant to standard of care treatment options or refused standard of care treatment or the participant's treating physician considers that the lack of standard of care treatment is not detrimental for the participant. * Measurable disease per RECIST v1.1, as assessed by Investigator. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and a life expectancy of at least 6 months. * Other Protocol defined inclusion criteria could apply.	* Primary platinum-refractory disease defined as disease progression during primary platinum-based chemotherapy or platinum-resistant disease defined as disease progression within 6 months of the platinum administration in either the first or second-line setting. * History of additional malignancy within 3 years before the date of enrollment. * Known brain metastases, unless clinically stable, that is without evidence of progression by imaging for at least 4 weeks prior to the first dose of study intervention, no evidence of new brain metastases, and on a stable or decreasing dose of ≤ 10 mg of prednisone (or equivalent) or without corticosteroids for at least 14 days prior to study intervention administration. * Active and/or uncontrolled infection. * History of known hypersensitivity to the active substances or to any excipients (e.g. polysorbate 80) of the study interventions. * Organ transplantation, including allogenic stem cell transplant. * Patients with history of drug-induced severe cutaneous adverse reaction (SCAR; including but not limited to Stevens-Johnson syndrome/toxic epidermal necrolysis \[SJS/TEN\], or drug reaction with eosinophilia and systemic symptoms \[DRESS\]), or dose-limiting immune-mediated reactions related to skin. * Other Protocol defined exclusion criteria could apply.

Inclusion Criteria

Exclusion Criteria

* Histologically or cytologically confirmed high grade serous or high grade endometrioid ovarian, primary peritoneal, and/or fallopian tube cancer that is recurrent.
* Participants whose tumor carries germline or somatic deleterious or suspected deleterious mutations in the genes BRCA1 (Breast Cancer gene 1) and BRCA2 (Breast Cancer gene 2), and/or tumors with positive HRD status. The presence of any of these mutations and/or the homologous recombination deficiency (HRD) status will be determined according to routinely used local standard of care tests. Results must be available before screening.
* Radiologically confirmed/documented disease progression while on Poly (ADP-ribose) polymerase (PARP) inhibitors therapy in either first or second-line maintenance setting (only 1 line of PARPi maintenance is allowed with or without bevacizumab). Note: Documentation of disease progression must be within 28 days of last PARPi dose taken. Surgical salvage intervention and/or focal ablative therapies are allowed, (further disease progression after these interventions must be documented), AND Clinically benefited from PARPi maintenance prior to documented progression, as defined by at least 6 months of treatment duration with no progressive disease observed, AND either, Progression on first-line maintenance PARPi: Participants are allowed maximum 1 additional line of platinum-based chemotherapy before study entry. (note: treatment-free interval on platinum rechallenge must be \>6 months, with documented disease progression prior to study entry).
* Intolerant to standard of care treatment options or refused standard of care treatment or the participant's treating physician considers that the lack of standard of care treatment is not detrimental for the participant.
* Measurable disease per RECIST v1.1, as assessed by Investigator.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and a life expectancy of at least 6 months.
* Other Protocol defined inclusion criteria could apply.

* Primary platinum-refractory disease defined as disease progression during primary platinum-based chemotherapy or platinum-resistant disease defined as disease progression within 6 months of the platinum administration in either the first or second-line setting.
* History of additional malignancy within 3 years before the date of enrollment.
* Known brain metastases, unless clinically stable, that is without evidence of progression by imaging for at least 4 weeks prior to the first dose of study intervention, no evidence of new brain metastases, and on a stable or decreasing dose of ≤ 10 mg of prednisone (or equivalent) or without corticosteroids for at least 14 days prior to study intervention administration.
* Active and/or uncontrolled infection.
* History of known hypersensitivity to the active substances or to any excipients (e.g. polysorbate 80) of the study interventions.
* Organ transplantation, including allogenic stem cell transplant.
* Patients with history of drug-induced severe cutaneous adverse reaction (SCAR; including but not limited to Stevens-Johnson syndrome/toxic epidermal necrolysis \[SJS/TEN\], or drug reaction with eosinophilia and systemic symptoms \[DRESS\]), or dose-limiting immune-mediated reactions related to skin.
* Other Protocol defined exclusion criteria could apply.

Contacts and Locations

Principal Investigator

Medical Responsible

STUDY_DIRECTOR

EMD Serono Research & Development Institute, Inc.

Study Locations (Sites)

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205

United States

University of California San Francisco - UCSF Medical Center

San Francisco, California, 94158

United States

Centricity Research Cancer Center - DBA CRRI John B. Amos Cancer Center Research

Columbus, Georgia, 31904

United States

University of Chicago Comprehensive Cancer Center at Silver Cross - Carolyn J. Czerkies Pavilion

Chicago, Illinois, 60637

United States

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, 48109

United States

Memorial Sloan Kettering Cancer Center

New York, New York, 10021

United States

Icahn School of Medicine at Mount Sinai PRIME - Mount Sinai - PRIME

New York, New York, 10029

United States

Next Oncology - Virginia

Fairfax, Virginia, 22031

United States

Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031

United States

Collaborators and Investigators

Sponsor: EMD Serono Research & Development Institute, Inc.

Medical Responsible, STUDY_DIRECTOR, EMD Serono Research & Development Institute, Inc.

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-10-30

Study Completion Date2028-01-25

Study Record Updates

Study Start Date2024-10-30

Study Completion Date2028-01-25

Terms related to this study

Keywords Provided by Researchers

Ataxia telangiectasia mutated Rad3-related
Ataxia telangiectasia mutated
Poly-ADP ribose polymerase inhibitor resistance
Homologous recombination deficiency

Additional Relevant MeSH Terms

Ovarian Cancer