Breast CancerPhase 1GEP14-LEECAPNCT02754011
Phase I Evaluating the Combination of Ribociclib+Capecitabine in Locally Advanced/Metastatic Breast Cancer HER2 Negative
A Phase 1 study testing Combination of ribociclib + capecitabine in people with Breast Cancer, run by UNICANCER at 2 sites in France.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Combination of ribociclib + capecitabine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 2 sitesFrance
- Study dates
- 2 Feb 2017to 23 Dec 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
- Patient information and written informed consent form signed
Who cannot join
- 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
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- 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
- Systolic blood pressure (SBP) >160 mmHg or <90 mmHg at screening
- Bradycardia (heart rate <50 at rest), by ECG or pulse, at screening
- On screening, inability to determine the QTcF interval on the ECG (i.e.: unreadable or not interpretable) or QTcF >450 msec (using Fridericia's correction). All as determined by screening ECG (mean of triplicate ECGs)
- Patient is currently receiving any of the following medications (see Table 9 for details) and cannot be discontinued 7 days prior to starting study drugs:
- Known strong inducers or inhibitors of CYP3A4/5, including grapefruit, grapefruits hybrids, pummelos, star-fruit, and Seville oranges
- That have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5
- That have a known risk to prolong the QT interval or induce Torsades de Pointes
- Herbal preparations/medications, dietary supplements
- Patient is currently receiving or has received:
- systemic corticosteroids within ≤ 2 weeks prior to starting study drug, or who have not fully recovered from side effects of such treatment. The following uses of corticosteroids are permitted: single doses, topical applications (e.g., for rash), inhaled sprays (e.g., for obstructive airways diseases), eye drops or local injections (e.g., intra-articular)
- sorivudine or brivudine within 4 weeks prior to starting capecitabine
- Patients with concurrent severe and/or uncontrolled concurrent medical conditions that would, in the investigator's judgement, cause unacceptable safety risks, contraindicate the participation in the study or compromise compliance with the protocol (e.g., uncontrolled hypertension and/or uncontrolled diabetes mellitus, clinically significant pulmonary disease, clinically significant neurological disorder, chronic pancreatitis, chronic active hepatitis, active untreated or uncontrolled fungal, bacterial or viral infections, etc.)
- Patient is currently receiving warfarin or other coumarin-derived anticoagulant for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH) or fondaparinux is allowed
- Participation in a prior investigational study within 30 days prior to enrolment or within 5 half-lives of the investigational product, whichever is longer
- Patient who has received radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study drug, or who has not recovered to grade 1 or better from related side effects of such therapy (exceptions include alopecia) and/or in whom ≥ 25% of the bone marrow was irradiated
- Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major side effects (tumor biopsy is not considered as major surgery)
- Patient has not recovered from all toxicities related to prior anticancer therapies to NCI-CTCAE version 4.03 Grade <1 (Exception to this criterion: patients with any grade of alopecia are allowed to enter the study)
- Patient with a Child-Pugh score B or C
- Patient has a concurrent malignancy or malignancy within 3 years of inclusion, with the exception of adequately treated, basal or squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer
- Patient has a history of non-compliance to medical regimen or inability to grant consent
- Pregnant (confirmed by a positive hCG laboratory test > 5mIU/mL) or lactating women
- Any condition which in the investigator's opinion makes it undesirable for the subject to participate in the trial or which would jeopardize compliance with the protocol
- Individuals deprived of liberty or placed under the authority of a tutor
Trial locations and contacts
2 sites in 1 country.
France2 sites
Centre Leon Berard
Lyon
Institut de Cancérologie de l'Ouest
Saint-Herblain
About this study
Official title: 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
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.
Read the 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
- Conditions
- Breast Cancer
- Being tested
- Combination of ribociclib + capecitabine
- Keywords
- HER2 negative, Locally advanced or metastatic
- Medical subject headings
- Breast Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Combination of ribociclib + capecitabineDrug
Also called Combination of LEE011 and XELODA
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
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Combination of ribociclib + capecitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From baseline to the end of cycle 1, up to 21 days
Secondary outcomes (5)
Evaluate safety of ribociclib and capecitabine combination
Toxicities are graded according to the CTCAE V4
Measured: 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
The objective of the pharmacokinetics is to investigate the interactions between ribociclib and capecitabine
Measured: From baseline to the end of cycle 1, up to 21 days
Evaluate the anti-tumor activity of ribociclib and capecitabine combination
Anti-tumor activity of the ribociclib and capecitabine combination will be carried out according to RECIST criteria version 1.1.
Measured: 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
Anti-tumor activity (At baseline and every 6 weeks) according to RECIST criteria version 1.1. and Toxicities according to the CTCAE V4
Measured: 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
Anti-tumor activity of the ribociclib and capecitabine combination will be carried out according to RECIST criteria version 1.1.
Measured: From baseline to disease progression or death from any cause, whichever comes first, up to 18 months (estimated treatment duration average: 6 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Apr 2016 (estimated)
- Study start2 Feb 2017
- Primary completion28 Feb 2022
- Study completion23 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by UNICANCERThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- UNICANCER
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Sponsor
- Investigators
- Thomas Bachelot, MD/PhD, Principal investigator, UNICANCER
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02754011
- Sponsor's protocol ID
- UC-0101/1504
- Acronym
- GEP14-LEECAP
- Status last verified
- Dec 2023
- First submitted
- 19 Feb 2016
- Last updated
- 7 Dec 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 7 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT02754011
- Acronym / sponsor ID
- GEP14-LEECAP / UC-0101/1504
- Conditions
- Breast Cancer
- Keywords
- HER2 negative, Locally advanced or metastatic
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- UNICANCERUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- 2 Feb 2017 (actual)
- Primary completion
- 28 Feb 2022 (actual)
- Study completion
- 23 Dec 2022 (actual)
- First posted
- 28 Apr 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| combination of ribociclib + capecitabine | Experimental | Drug: Combination of ribociclib + capecitabineRIBOCICLIB 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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
Key exclusion criteria (38 listed)
- 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:
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Combination of ribociclib + capecitabineAlso: Combination of LEE011 and XELODARIBOCICLIB 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 |
Primary outcome
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.
5 secondary outcomes
Evaluate safety of ribociclib and capecitabine combination
Time frame: 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
Time frame: From baseline to the end of cycle 1, up to 21 days
Evaluate the anti-tumor activity of ribociclib and capecitabine combination
Time frame: 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
Time frame: 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
Time frame: From baseline to disease progression or death from any cause, whichever comes first, up to 18 months (estimated treatment duration average: 6 months)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Dec 2023.
- Unicancer official websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Thomas Bachelot, MD/PhD principal investigator
UNICANCER
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Combination of ribociclib + capecitabine in people with Breast Cancer, run by UNICANCER at 2 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 38 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Dec 2023.