Phase I Evaluating the Combination of Ribociclib+Capecitabine in Locally Advanced/Metastatic Breast Cancer HER2 Negative

NCT02754011 | Completed Phase 1 DMC

• 1 other identifier: UC-0101/1504
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

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.

Conditions

Breast Cancer

Keywords

HER2 negative; Locally advanced or metastatic

Outcome Measures

Primary Outcomes (1)

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

  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.

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

Secondary Outcomes (5)

• 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

• 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 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)

Study Arms (1)

combination of ribociclib + capecitabine

EXPERIMENTAL

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

Drug: Combination of ribociclib + capecitabine

Interventions

Combination of ribociclib + capecitabine DRUG

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

Also known as: Combination of LEE011 and XELODA

combination of ribociclib + capecitabine

Eligibility Criteria

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

You may qualify if:

• 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
• Adequate hepatic function: total bilirubin ≤ ULN, or total bilirubin ≤ 3.0 x ULN or direct bilirubin ≤ 1.5 x ULN in patients with well documented Gilbert's Syndrome, ALAT and ASAT ≤ 2.5 x ULN (regardless of the presence or absence of liver metastasis)
• Adequate renal function: serum creatinine ≤ 1.5 mg/dL or creatinine clearance ≥ 50 mL/min
• Adequate ionic balance: potassium, total calcium (corrected for serum albumin), magnesium, sodium and phosphorus within normal limits for the institution or corrected to within normal limits with supplements before first dose of study medication
• Women of child-bearing potential must agree to use an effective contraceptive method while on treatment and for 8 weeks after study drugs discontinuation. Highly effective contraception methods are detailed in section 6.1.1.
• Patient must be affiliated to a Social Security system

You may not qualify if:

• 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
• History of documented congestive heart failure (New York Heart Association functional classification III-IV)
• Documented cardiomyopathy
• Patient has a Left Ventricular Ejection Fraction (LVEF) \< 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening
• History of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality within 12 months of screening
• Congenital long QT syndrome or family history of long QT syndrome

Sponsors & Collaborators

• UNICANCER: lead
• Novartis: collaborator

Study Sites (2)

Centre Leon Berard

Lyon, France

Location

Institut de Cancérologie de l'Ouest

Saint-Herblain, France

Location

Related Links

• Unicancer official website

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis

Interventions

Capecitabine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Thomas Bachelot, MD/PhD

  UNICANCER

  PRINCIPAL INVESTIGATOR

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: February 19, 2016
• First Posted: April 28, 2016
• Study Start: February 2, 2017
• Primary Completion: February 28, 2022
• Study Completion: December 23, 2022
• Last Updated: December 7, 2023

Record last verified: 2023-12

Locations

FR (2)