A Phase 1b/2 Trial Evaluating Safety and Efficacy of CAPecitabine in Combination With Ni-rapaRIb in HER2-negative Advanced Breast canCEr

NCT05519670 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: CAPRICE-IPC 2020-053
• Study Type: interventional
• Target: 72
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study will be to combine oral capecitabine and oral niraparib such thz association may increase clinical benefits of PARP inhibitors in germline BRCA mutated HER2 negative advanced breast cancer patients.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Dose-Limiting Toxicities (DLT)

  incidence of Dose-Limiting Toxicities (DLT)

  3 weeks

• efficacy with objective response rate (ORR)

  rate of patients experiencing an objective response

  6 months

Secondary Outcomes (2)

• adverse events

  6 months

• Pharmacokinetics (PK)

  15 days

Study Arms (1)

Only Arm

EXPERIMENTAL

niraparib + capecitabine treatment

Drug: Niraparib Oral Product

Interventions

Niraparib Oral Product DRUG

Niraparib + capecitabine treatment

Only Arm

Eligibility Criteria

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

You may qualify if:

• Women or men aged 18 or more
• Histologically-confirmed advanced breast cancer (metastatic or locally advanced)
• Tumor without overexpression of HER2 (HER2 1+ in IHC, or IHC 2+ and FISH/ CISH negative) in samples from the primary and/or secondary tumor
• Hormone receptor status known
• Endocrine insensitive (hormone receptor negative or Endocrine (aromatase inhibitor)-resistant (a CDK4/6-based endocrine treatment must have been administered as a first-line of second-line treatment, unless primary endocrine-refractory disease as defined as relapse within the first 2 years of aromatase-based adjuvant endocrine therapy or progression under endocrine treatment administered for metastatic disease within 6 months of initiation))
• Progressive disease patients who are eligible to a treatment with capecitabine: after fail-ure to taxanes and anthracycline-based chemotherapy (unless contraindicated) (neoadjuvant, adjuvant or metastatic setting)
• A representative tumor specimen must be available for molecular testing. An archival tu-mor sample may be submitted (\<6 months); however, if one is not available, a newly obtained tumor biopsy specimen must be submitted instead
• Measurable disease according to RECIST1.1
• Symptomatic, untreated, or actively progressing central nervous system (CNS) metasta-ses are not eligible. Patients with a history of treated CNS lesions are eligible, provided all of the following criteria are met:
• Measurable or non-measurable disease, per RECIST v. 1.1, must be present outside the CNS
• No history of intracranial haemorrhage or spinal cord haemorrhage
• Metastases are limited to the cerebellum or the supratentorial region (i.e., no metasta-ses to the midbrain, pons, medulla, or spinal cord).
• There is no evidence of interim progression between completion of CNS-directed ther-apy and the screening brain scan.
• The patient has not received stereotactic radiotherapy within 7 days prior to initiation of study treatment or whole-brain radiotherapy within 14 days prior to initiation of study treatment.
• The patient has no ongoing requirement for corticosteroids as therapy for CNS disease. Anticonvulsant therapy at a stable dose is permitted.

You may not qualify if:

• Prior treatment with a PARP inhibitor and capecitabine for metastatic disease, (Patients treat-ed with these drugs in the adjuvant setting are allowed to participate if they experienced 2 years from end of treatment and metastatic relapse)
• Patient has a Dihydropyrimidine dehydrogenase deficiency (DPD)
• Patients must not have received anticancer chemotherapy, targeted therapy within 2 weeks prior of the study. Endocrine therapy must have been discontinued 7 or more days before Cycle 1 Day 1. Participant must not have had investigational therapy administered within 4 weeks or with-in a time interval less than at least 5 half-lives of the investigational agent, whichever is longer, prior to the first scheduled day of dosing in this study.
• Palliative radiotherapy must have been completed 14 or more days before Cycle 1 Day 1. Biphosphonates and denosumab are allowed.
• Major surgery within 3 weeks prior to registration. Patients must have recovered from earlier major surgery before registration.
• Persistent toxicities (≥NCI-CTCAE grade 2) caused by previous cancer therapy, excluding alopecia and NCI-CTCAE grade 2 peripheral neuropathy.
• Immunocompromised patients (e.g. HIV) for part I and but patients with well controlled HIV could be included in part II (negative viral load)
• Patients considered at poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection, symptomatic congestive heart fail-ure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses, or Posterior Reversible Encephalopathy Syn-drome (PRES).
• Mean resting QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 consecutive electrocardiograms using Fridericia's Correction.
• Active or prior documented inflammatory bowel disease (Crohn's disease, ulcerative colitis).
• Patients unable to swallow orally administered medication, patients with gastrointestinal dis-orders likely to interfere with absorption of niraparib, and patients with long-term oral anticoagu-lant therapy.
• Pregnant or breast-feeding women. Participant must agree to not breastfeed during the study and for 30 days after the last dose of study treatment
• Known hypersensitivity to niraparib or capecitabine or any of the excipients of the products
• Patient is currently receiving or has received sorivudine or brivudine within 4 weeks prior to starting capecitabine
• Patient has received a transfusion (platelets or red blood cells) ≤ 4 weeks prior to initiating protocol therapy

Sponsors & Collaborators

• Institut Paoli-Calmettes: lead
• GlaxoSmithKline: collaborator

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Central Study Contacts

CECILE VICIER, DR

CONTACT

+33 4 91 22 38 47; vicierc@ipc.unicancer.fr

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2022
• First Posted: August 29, 2022
• Study Start: March 1, 2023
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: August 29, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share