Dose-escalation, Phase I Multicentric Trial, Evaluating the Combination of Ribociclib and Capecitabine in Locally Advanced or Metastatic Breast Cancer HER2 Negative in Patients Previously Treated With Anthracyclines and Taxanes

UNICANCER2 sites in 1 country18 target enrollmentFebruary 2, 2017

ConditionsBreast Cancer

InterventionsCombination of ribociclib + capecitabine

DrugsCombination of ribociclib + capecitabine

Overview

Phase: Phase 1
Intervention: Combination of ribociclib + capecitabine
Conditions: Breast Cancer
Sponsor: UNICANCER
Enrollment: 18
Locations: 2
Primary Endpoint: Determination of the maximum tolerated dose (MTD) and the recommended dose for phase 2 (RP2D) of ribociclib and capecitabine combination
Status: Completed
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The proposed study is a multicenter, open-label phase I trial, conducted in locally advanced or metastatic breast cancer HER2 negative patients and divided into 2 parts:

STEP 1: a dose escalation part (n= up to 30) to evaluate the safety profile and pharmacokinetics and to define the MTD and RP2D to recommend in a phase II.
STEP 2: an expansion cohort part to confirm the safety and tolerability of ribociclib and capecitabine association on a longer follow-up, and to obtain preliminary evidence of anti-tumor activity on two expanded cohorts of HR positive and HR negative patients. Up to 14 patients in each cohort, taking into account patients already included in step one at this DL, may be enrolled, for a total of 28 at the RP2D.

Detailed Description

Patients with HER2 negative locally advanced or metastatic breast cancer, eligible to a capecitabine treatment as required by its approved indication, i.e previously treated with anthracyclines and taxanes

Registry

clinicaltrials.gov

Start Date

February 2, 2017

End Date

December 23, 2022

Last Updated

2 years ago

Study Type

Interventional

Study Design

Single Group

Sex

Female

Investigators

Sponsor

UNICANCER

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Women aged 18 or more
•Histologically-confirmed advanced breast cancer (metastatic or locally advanced)
•Progressive patients who are eligible to a treatment with capecitabine: after failure to taxanes (neoadjuvant, adjuvant or metastatic setting) and failure to prior anthracycline-based chemotherapy (unless contraindicated)
•Tumor no overexpressing HER2 (HER2 1+ in IHC, or IHC 2+ and FISH/ CISH negative) in samples from the primary and/or secondary tumor
•A representative tumor specimen must be available for future research programs. An archival tumor sample may be submitted; however, if one is not available, a newly obtained tumor biopsy specimen must be submitted instead
•Measurable or evaluable disease according to RECIST v1.1 criteria
•Patients must be able to swallow tablets and capsules
•Patients must have an estimated survival of at least 3 months
•WHO performance status (ECOG) from 0 to 1
•Adequate hematological and coagulation function: Hb ≥ 9.0 g/dL, ANC ≥ 1500/mm³ platelets ≥ 100 000/mm³, INR ≤ 1.5

Exclusion Criteria

•Patient has been pre-treated by CDK inhibitor or capecitabine
•Patient has a DPD deficiency
•Patient has a known hypersensitivity to to 5-FU or to any of the excipients of ribociclib or capecitabine
•Patients with central nervous system (CNS) involvement unless they meet ALL of the following criteria:
•At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment
•Clinically stable CNS tumor at the time of screening and not receiving steroids and/or enzyme-inducing anti-epileptic medications for brain metastases
•Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
•Patient has a known history of HIV infection (testing not mandatory)
•Clinically significant, uncontrolled heart disease and/or recent events including any of the following:
•History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 12 months prior to screening

Arms & Interventions

combination of ribociclib + capecitabine

RIBOCICLIB from 200 to 600mg once daily + CAPECITABINE from 750 to 1000 mg/m² BID, cycles are defined in 21-day periods, 2 weeks on treatment, 1 week off treatment

Intervention: Combination of ribociclib + capecitabine

Outcomes

Primary Outcomes

Determination of the maximum tolerated dose (MTD) and the recommended dose for phase 2 (RP2D) of ribociclib and capecitabine combination

Time Frame: From baseline to the end of cycle 1, up to 21 days

Determination of MTD and RP2D of ribociclib and capecitabine combination, PO in a 21 day schedule (2 weeks on/1 week off), in subjects eligible to a capecitabine treatment, with locally advanced/metastatic breast cancer who failed anthracycline and taxane treatment.

Secondary Outcomes

Characterize the pharmacokinetic (PK) profile of ribociclib and capecitabine combination(From baseline to the end of cycle 1, up to 21 days)
Evaluate the anti-tumor activity of ribociclib and capecitabine combination(From baseline to disease progression or death from any cause, whichever comes first, up to 18 months (estimated treatment duration average: 6 months))
Evaluate anti-tumor activity and safety of the ribociclib and capecitabine combination RP2D according to RH status(From baseline to disease progression or death from any cause, whichever comes first, up to 18 months (estimated treatment duration average: 6 months))
Evaluate safety of ribociclib and capecitabine combination(Toxicities will be assessed during the whole treatment period (6 months expected in average) followed by a 1-year post-treatment follow-up period, and reported during the visits scheduled by the study flow chart)
Evaluate the anti-tumor activity of ribociclib and capecitabine depending on Rb status(From baseline to disease progression or death from any cause, whichever comes first, up to 18 months (estimated treatment duration average: 6 months))