A Study Evaluating Safety and Efficacy of Niraparib in Patients With Previously Treated Metastatic Esophageal/Gastroesophageal Junction/Proximal Gastric Adenocarcinoma

NCT03840967 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: HCRN ESO17-325
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 4

Brief Summary

Patients can be prescreened for the study at the time of diagnosis of locally advanced or metastatic disease by determining presence of LOH high status and/or deleterious alterations in HR pathway genes in the most recent available tumor tissue sample or in blood if they are found to have germline mutations. Patients with either somatic or germline mutations will be allowed. At the time of disease progression, patients with high LOH or deleterious alterations in HR pathway genes and satisfying all other inclusion criteria will be enrolled on the study. Patients will be treated with niraparib (flat dose) orally every day for 28 days until disease progression, unacceptable side effects, withdrawal of consent, or death. CT of the chest/abdomen/pelvis will be performed every 2 months and response will be assessed by RECIST 1.1.

Conditions

Esophageal Cancer; Gastric Cancer; Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. ORR is defined as the percentage of patients who reached CR or PR by RECIST 1.1.

  Up to maximum of 5 months.

Secondary Outcomes (3)

• Adverse Events

  AE had been recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) or until a new anti-cancer treatment starts, whichever occurs first, up to a maximum of 6 months.

• Progression Free Survival (PFS)

  Up to a maximum of 5 months.

• Disease Control Rate

  Up to maximum of 5 months.

Study Arms (1)

Niraparib

OTHER

Drug: Niraparib

Interventions

Niraparib DRUG

Niraparib will be administered as a flat-fixed daily dose depending on weight and platelet count. Subjects will take orally on a daily basis for 28 days. Each cycle = 28 days

Also known as: Zejula

Niraparib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Age ≥ 18 years at the time of consent.
• ECOG Performance Status of 0-1 within 14 days prior to registration.
• Locally advanced esophageal adenocarcinoma or proximal gastric adenocarcinoma or metastatic adenocarcinoma originating from esophagus, GE junction, or proximal stomach who progress/recur beyond 2 months of receiving a platinum- containing regimen
• NOTE: Patients can be pre-screened for study at any time including after surgical resection for locally advanced esophageal cancer, at presentation with metastatic disease and potentially during chemotherapy and radiation prior to surgery.
• A subject with symptomatic brain metastasis may be considered if they have completed their treatment for brain metastasis at least 4 weeks prior to study registration, have been off of corticosteroids for ≥ 2 weeks, and are asymptomatic. Patients with asymptomatic brain mets that are untreated will be allowed.
• Must not have received more than 1 prior line of chemotherapy in the metastatic setting (could have received immunotherapy, VEGF directed therapy, and/or trastuzumab which does not count as chemotherapy).
• One of the following genetic results is required for eligibility:
• High LOH in tissue OR
• HR mutation in tissue OR
• Germline mutation (blood)
• NOTE: Genetic testing results from a CLIA certified lab that confirm one of the following: high LOH in tissue, HR mutation in tissue or germline mutation in blood are required and can be used to meet eligibility. Even if subject has met eligibility with one of the criteria above, results from the other analysis is required if available.
• If prior genetic results are not available, subject must have archival tissue or fresh tissue (by new biopsy) for testing. Both primary tumor tissue and metastatic site sample biopsies are allowed. Blood will also be required for germline mutation analyses. Central confirmation of all results will be performed but are not mandated for eligibility. If a subject has met eligibility with prior genetic results but does not have sufficient archival tissue for central confirmation, a biopsy is not required.
• Presence of measurable disease by RECIST v1.1, defined as:
• Tumor lesions that must be accurately measured in at least one dimension (longest diameter in the plane of measurement is to be recorded) with a minimum size of:

You may not qualify if:

• Prior therapy with a PARP inhibitor
• Disease progression during first 2 months of standard dose platinum-based chemotherapy (platinum refractory). This excludes low dose platinum based therapy that is given in a chemotherapy-radiation regimen for locally advanced esophageal cancer.
• Participant must not be simultaneously enrolled in any other interventional clinical trial.
• Participant must not have had major surgery ≤ 3 weeks prior to initiating protocol therapy and participant must have recovered from any surgical effects.
• Participant must not have received investigational therapy ≤ 4 weeks, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is shorter, prior initiating protocol therapy.
• Participant has had radiation therapy encompassing \>20% of the bone marrow within 2 weeks; or any radiation therapy within 1 week prior to Day 1 of protocol therapy.
• Participant must not have a known hypersensitivity to niraparib components or excipients including tartrazine.
• Participant must not have received a transfusion (platelets or red blood cells) ≤ 4 weeks prior to initiating protocol therapy.
• Participant must not have received colony stimulating factors (e.g., granulocyte colony-stimulating factor, granulocyte macrophage colony stimulating factor, or recombinant erythropoietin) within 4 weeks prior initiating protocol therapy.
• Participant has had any known Grade 3 or 4 anemia, neutropenia or thrombocytopenia due to prior chemotherapy that persisted \> 4 weeks and was related to the most recent treatment.
• Participant must not have any known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
• Participant must not have a serious, uncontrolled medical disorder, nonmalignant systemic disease, or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 90 days) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent.
• No active secondary cancer

Sponsors & Collaborators

• Shadia Jalal, MD: lead
• GlaxoSmithKline: collaborator
• Indiana University School of Medicine: collaborator

Study Sites (4)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Indiana Univeristy Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

University of Michigan Health System

Ann Arbor, Michigan, 48109, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

MeSH Terms

Conditions

Esophageal Neoplasms; Stomach Neoplasms; Adenocarcinoma

Interventions

niraparib

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Stomach Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Results Point of Contact

• Title: Fauzia Sharmin
• Organization: Hoosier Cancer Research Network

fsharmin@hoosiercancer.org

317-921-2050

Study Officials

• Shadia Jalal, MD

  Indiana University Melvin and Bren Simon Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: February 12, 2019
• First Posted: February 15, 2019
• Study Start: July 9, 2019
• Primary Completion: November 17, 2022
• Study Completion: February 22, 2023
• Last Updated: June 4, 2024
• Results First Posted: June 4, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)