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NCT03840967

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

Terminated Phase 2 Results posted Last updated 4 June 2024
What this trial tests

Phase 2 trial testing Niraparib in Esophageal Cancer in 14 participants. Terminated before completion.

Timeline
9 July 2019
Primary endpoint
17 November 2022
22 February 2023

Quick facts

Lead sponsorShadia Jalal, MD
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment14
Start date9 July 2019
Primary completion17 November 2022
Estimated completion22 February 2023
Sites4 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Shadia Jalal, MD

Who can join

18 and older, any sex, with Esophageal Cancer or Gastric Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Objective Response Rate (ORR) Primary · Up to maximum of 5 months.

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.

GroupValue95% CI
Niraparib0
Adverse Events Secondary · 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.

Number of participants with treatment related adverse events are reported by CTCAEv5 term and grade.

Anemia
GroupValue95% CI
Niraparib7
Fatigue
GroupValue95% CI
Niraparib7
Platelet count decreased
GroupValue95% CI
Niraparib7
Nausea
GroupValue95% CI
Niraparib6
Headache
GroupValue95% CI
Niraparib5
White blood cell decreased
GroupValue95% CI
Niraparib5
Anorexia
GroupValue95% CI
Niraparib3
Constipation
GroupValue95% CI
Niraparib3
Progression Free Survival (PFS) Secondary · Up to a maximum of 5 months.

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. PFS is defined as time from treatment start until disease progression met by RECIST 1.1 or death from any cause.

GroupValue95% CI
Niraparib1.81 – 3.7
Disease Control Rate Secondary · Up to maximum of 5 months.

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. Disease control rate (DCR) is defined as the percentage of evaluable patients with stable disease (SD) for 8 weeks, or partial response (PR), or complete response (CR) according to RECIST 1.1.

GroupValue95% CI
Niraparib18.22.3 – 51.8

Adverse events — posted to ClinicalTrials.gov

Time frame: All-Cause Mortality was monitored up to a maximum of 24 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 6 months.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Niraparib
Serious: 3/14 (21%)
Deaths: 12/14

Serious adverse events (3 terms)

ReactionSystemNiraparib
ASPIRATIONRespiratory, thoracic and mediastinal disorders
SEPSISInfections and infestations
VOMITINGGastrointestinal disorders
Other adverse events (59 terms — click to expand)

ReactionSystemNiraparib
ANEMIABlood and lymphatic system disorders
FATIGUEGeneral disorders
HEADACHENervous system disorders
PLATELET COUNT DECREASEDInvestigations
NAUSEAGastrointestinal disorders
CONSTIPATIONGastrointestinal disorders
WHITE BLOOD CELL DECREASEDInvestigations
ALKALINE PHOSPHATASE INCREASEDInvestigations
ANOREXIAMetabolism and nutrition disorders
ASPARTATE AMINOTRANSFERASE INCREASEDInvestigations
SURGICAL AND MEDICAL PROCEDURES - OTHER, SPECIFYSurgical and medical procedures
WEIGHT LOSSInvestigations
ABDOMINAL PAINGastrointestinal disorders
BACK PAINMusculoskeletal and connective tissue disorders
CREATININE INCREASEDInvestigations
DIARRHEAGastrointestinal disorders
DIZZINESSNervous system disorders
DYSPEPSIAGastrointestinal disorders
FEVERGeneral disorders
HYPOCALCEMIAMetabolism and nutrition disorders
INSOMNIAPsychiatric disorders
NEUTROPHIL COUNT DECREASEDInvestigations
VOMITINGGastrointestinal disorders
ALANINE AMINOTRANSFERASE INCREASEDInvestigations
COUGHRespiratory, thoracic and mediastinal disorders
DYSPNEARespiratory, thoracic and mediastinal disorders
HYPOKALEMIAMetabolism and nutrition disorders
HYPOMAGNESEMIAMetabolism and nutrition disorders
HYPOTENSIONVascular disorders
INVESTIGATIONS - OTHER, SPECIFYInvestigations
LYMPHOCYTE COUNT DECREASEDInvestigations
PAINGeneral disorders
ALOPECIASkin and subcutaneous tissue disorders
ANXIETYPsychiatric disorders
ARTHRALGIAMusculoskeletal and connective tissue disorders
BLOOD BILIRUBIN INCREASEDInvestigations
CHILLSGeneral disorders
DRY MOUTHGastrointestinal disorders
DRY SKINSkin and subcutaneous tissue disorders
DYSGEUSIANervous system disorders

Most-reported serious reactions: ASPIRATION, SEPSIS, VOMITING.

Data from ClinicalTrials.gov NCT03840967 adverse events section.

Sponsor's own description

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.

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

  1. PARP inhibitors in gastric cancer: beacon of hope.
    Wang Y, Zheng K, Huang Y, Xiong H, et al · · 2021 · cited 42× · PMID 34167572 · DOI 10.1186/s13046-021-02005-6
  2. The potential of PARP inhibitors in targeted cancer therapy and immunotherapy.
    Hunia J, Gawalski K, Szredzka A, Suskiewicz MJ, et al · · 2022 · cited 25× · PMID 36533080 · DOI 10.3389/fmolb.2022.1073797
  3. Therapeutic Potential of PARP Inhibitors in the Treatment of Gastrointestinal Cancers.
    Alhusaini A, Cannon A, Maher SG, Reynolds JV, et al · · 2021 · cited 18× · PMID 34440228 · DOI 10.3390/biomedicines9081024
  4. Targeting BRCA and DNA Damage Repair Genes in GI Cancers: Pathophysiology and Clinical Perspectives.
    Zimmer K, Kocher F, Puccini A, Seeber A. · · 2021 · cited 17× · PMID 34707985 · DOI 10.3389/fonc.2021.662055
  5. Hereditary Gastric Cancer: Single-Gene or Multigene Panel Testing? A Mono-Institutional Experience.
    Calvello M, Marabelli M, Gandini S, Marino E, et al · · 2023 · cited 6× · PMID 37239438 · DOI 10.3390/genes14051077
  6. Exceptional synergistic response of PARP inhibitor and immune checkpoint inhibitor in esophageal adenocarcinoma with a germline BRCA2 mutation: a case report.
    Mahadevia H, Ponvilawan B, Al-Obaidi A, Buckley J, et al · · 2024 · cited 2× · PMID 38559611 · DOI 10.1177/17588359241242406
  7. Circular RNA circATM binds PARP1 to suppress Wnt/β-catenin signaling and induce cell cycle arrest in gastric cancer cells.
    Zhu X, Zhang X, Qin Y, Chen Y, et al · · 2026 · cited 1× · PMID 40288674 · DOI 10.1016/j.jare.2025.04.033

Verify or expand the search:

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