A phase II study assessing safety and efficacy of Cabozantinib for advanced or metastatic cervical carcinoma after platinum treatment failure

Phase 1

• Conditions: Recurrent unresectable or metastatic cervix carcinoma; MedDRA version: 21.1Level: PTClassification code 10008344Term: Cervix carcinoma recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-002184-97-FR
• Lead Sponsor: Centre François Baclesse

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-10-18
• Last Update Posted: 17 January 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 57

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:
oAbsolute neutrophil count (ANC) = 1000/mm3 (= 1.0 GI/L)
oPlatelets = 100,000/mm3 (= 100 GI/L)
oHemoglobin = 10 g/dL (= 100 g/L) (red blood cell transfusion is allowed)
oTotal bilirubin = 1.5 fold the upper limit of normal (for subjects with Gilbert’s disease, = 3 mg/dL or = 51.3 µmol/L)
oSerum albumin = 2.8 g/dL (= 28 g/L)
oCalculated creatinine clearance = 50 mL/min by the Cockcroft –Gault method
oAlanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3.0 x the upper limit of normal
oUrine protein/creatinine ratio (UPCR) = 1 (= 113.17 mg/mmol creatinine)
oSerum potassium = lower limit of normal
oSerum calcium = lower limit of normal
oSerum magnesium = lower limit of normal
-Corrected QT interval calculated by the Fridericia formula (QTcF) > 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

-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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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<br>-The objective response (RECIST v1.1 criteria)<br>-The progression-free and overall survival<br>-The health-related quality-of-life (QoL) of patients<br>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:<br>•Efficacy: assessed by the proportion of patients with disease control rate 3 months after cabozantinib treatment initiation. <br>•Safety assessed by the proportion of patients with fistula<br>;Timepoint(s) of evaluation of this end point: 3 months after cabozantinib treatment initiation