Recurrent unresectable or metastatic cervix carcinoma MedDRA version: 21.1 Level: PT Classification code 10008344 Term: Cervix carcinoma recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: CABOZANTINIB
Product Name: CABOMETYX
Pharmaceutical Form: Coated tablet
INN or Proposed INN: CABOZANTINIB
CAS Number: 849217-68-1
Concentration unit: mg milligram(s)
Concentration type: ra
Sponsors
Centre François Baclesse
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Female 18 years of age or older - Histologically confirmed recurrent unresectable or metastatic cervix carcinoma - Patient may have received at least one prior chemotherapy regimen of platinum-based chemotherapy for recurrence or metastatic disease. Cisplatin given in combination with radiation for a localized disease does not count as a prior chemotherapy. Prior treatment for advanced/metastatic disease with bevacizumab is allowed. Prior treatments with immune checkpoint inhibitors are allowed. - ECOG performance status 0-2 - Measurable disease per RECIST 1.1 - The subject must have recovered to baseline or CTCAE v.5.04.0 (Common Terminology Criteria for Adverse Events, version 54.0) = Grade 1 from clinical toxicities related to any prior treatments, i.e chemotherapy or pelvis radiation unless AE(s) are clinically non-significant (for example alopecia) - Adequate organ and marrow function, defined as follows, based upon laboratory tests performed within 7 days before randomizationinclusion: o Absolute neutrophil count (ANC) = 1000/mm3 (= 1.0 GI/L) o Platelets = 100,000/mm3 (= 100 GI/L) o Hemoglobin = 10 g/dL (= 100 g/L) (red blood cell transfusion is allowed) o Total bilirubin = 1.5 fold the upper limit of normal (for subjects with Gilbert’s disease, = 3 mg/dL or = 51.3 µmol/L) o Serum albumin = 2.8 g/dL (= 28 g/L) o Calculated creatinine clearance = 50 mL/min by the Cockcroft –Gault method o Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) 450 msec - Left-ventricular ejection fraction = 50% - Subjects affiliated to an appropriate social security system - Female subjects of childbearing potential must not be pregnant at screening and during treatment by Cabozantinib. Effective methods of contraception should be used throughout the course of treatment and for at least 4 months after the end of treatment. Sexually active fertile subjects and their partners must agree to use medically accepted barrier methods of contraception (e.g., male or female condom) during the study and 4 months after the last dose of study treatment, even if oral contraceptives are also used. - Before patient registration, written informed consent must be given according to ICH/GCP, and national/local regulations. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 57 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 57
Exclusion criteria
Exclusion criteria: - Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding and/or fistula/perforation including, but not limited to: Active peptic ulcer disease, inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment. - Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to: malabsorption syndrome, major resection of the stomach or small bowel. - History of any one or more of the following cardiovascular conditions within the past 6 months: Cardiac angioplasty or stenting, myocardial infarction, unstable angina, coronary artery bypass graft surgery, symptomatic peripheral vascular disease, class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA). - Uncontrolled hypertension defined as systolic blood pressure (SBP) of > 140 mmHg or diastolic blood pressure (DBP) of > 90 mmHg despite an optimal treatment. - History of cerebrovascular accident including transient ischemic attack (TIA), symptomatic pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months. Note: Subjects with recent DVT or asymptomatic pulmonary embolism who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible. - Major surgery or trauma within 28 days prior to first dose of investigational product and/or presence of any non-healing wound, fracture, or ulcer. - Evidence of active bleeding or pathologic conditions that carry high risk of bleeding such as known bleeding disorders, coagulopathy or tumor involving major vessels. - Any external radiation therapy within 4 weeks before randomization. - Presence of brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 3 months before randomization. Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of randomization. - Concomitant use of known strong CYP3A4 inhibitors or inducers. - Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial - Patients with second primary cancer, except adequately treated non-melanoma skin cancer, or other solid tumors curatively treated with no evidence of disease for = 3 years - Concurrent participation in any therapeutic clinical trial - Patient deprived of liberty or placed under the authority of a tutor
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess efficacy and safety of cabozantinib in monotherapy in advanced/metastatic cervical cancer (CC) after failure of platinum-based regimen treatment.;Secondary Objective: - The safety profile of cabozantinib - The objective response (RECIST v1.1 criteria) - The progression-free and overall survival - The health-related quality-of-life (QoL) of patients To constitute biological collections (blood, tumoral tissue) for further biological explorations;Primary end point(s): The main objective will be based on joint primary endpoints of efficacy and safety as proposed by the Bryant-and-Day design: • Efficacy: assessed by the proportion of patients with disease control rate 3 months after cabozantinib treatment initiation. • Safety assessed by the proportion of patients with fistula ;Timepoint(s) of evaluation of this end point: 3 months after cabozantinib treatment initiation | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints are : o Progression-free survival, defined as the time between initiation of cabozantinib treatment and progression (RECIST 1.1 criteria) or death of any cause whichever occurs first. o Overall survival, defined as the time between initiation of cabozantinib treatment and death of whatever cause. o Toxicities evaluated according to NCI CTCAE v5.04.03 criteria, in terms of kind, grade, time of onset, reversibility o Significant toxicities responsible for interruption or dose reduction of cabozantinib treatment o Proportion of patients requiring cabozantinib dose reduction or treatment stopping for toxicity o Objective response rate defined as the percentage of patients who have achieved complete response or partial response with RECIST 1.1 criteria. o Scores of Quality-of-life according to self-administered questionnaire: EORTC QLQ-C30 and its additional cervix cancer module (QLQ–CX24) ;Timepoint(s) of evaluation of this end point: At the end of study | — |
Countries
France
Contacts
Public ContactChef de Projet/recherche clinique
Centre François Baclesse
Outcome results
None listed