Cabozantinib for Advanced or Metastatic Cervical Carcinoma After Platinum Treatment Failure

NCT04205799 | Completed Phase 2 DMC

• 1 other identifier: 2019-002184-97
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 8

Brief Summary

Assess efficacy and safety of cabozantinib in monotherapy in advanced/metastatic cervical cancer (CC) after failure of platinum-based regimen treatment.

Conditions

Advanced/Metastatic Cervical Cancer

Keywords

cervical cancer; advanced/metastatic; Cabozantinib; platinum treatment failure

Outcome Measures

Primary Outcomes (2)

• efficacy of cabozantinib: proportion of patients with disease control rate

  Efficacy assessed by the proportion of patients with disease control rate

  3 months after cabozantinib treatment initiation.

• Safety of cabozantinib: proportion of patients with clinical gastro-intestinal (GI) perforation/fistula, GI-vaginal fistula and genito-urinary (GU) fistula events grade ≥ 2 (NCI CTCAE v 5.0)

  Safety assessed by the proportion of patients with clinical gastro-intestinal (GI) perforation/fistula, GI-vaginal fistula and genito-urinary (GU) fistula events grade ≥ 2 (NCI CTCAE v 5.0)

  toxicities occurring up to 1 month after the end of treatment

Secondary Outcomes (5)

• Objective response (RECIST v1.1 criteria)

  At the end of cycle 3,6,9... (each cycle is 28 days) through study completion, an average of 1 year

• Progression-free survival (PFS)

  At the end of cycle 3,6,9... (each cycle is 28 days) through study completion, an average of 1 follow-up year

• Overall survival

  through study completion, an average of 1 follow-up year

• Safety profile of cabozantinib

  every cycle of treatment (each cycle is 28 days) through study completion, an average of 1 follow-up year

• Incidence of treatment Quality-of-life of patients assessed by EORTC QLQ-C30 /CX24 questionnaire

  At Day 15 of cycle 2 (each cycle is 28 days) and every 3 cycles of treatment ((every 12 weeks)) an average of 1 follow-up year

Study Arms (1)

CABOZANTINIB

EXPERIMENTAL

Cabozantinib will be administered at the daily dose of 60 mg given orally in a 4-week cycle. It will be continued without interruption until disease progression or discontinuation for any cause.

Drug: Cabozantinib

Interventions

Cabozantinib DRUG

Cabozantinib will be administered at the daily dose of 60 mg given orally in a 4-week cycle. It will be continued without interruption until disease progression or discontinuation for any cause.

CABOZANTINIB

Eligibility Criteria

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

You may qualify if:

• Female 18 years of age or older
• Histologically confirmed recurrent unresectable or metastatic cervix carcinoma with squamous cell, adenocarcinoma or adenosquamous histology - - 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.5.0 (Common Terminology Criteria for Adverse Events, version 5.0) ≤ 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)
• Absolute neutrophil count (ANC) ≥ 1000/mm3 (≥ 1.0 GI/L)
• Platelets ≥ 100,000/mm3 (≥ 100 GI/L)
• Hemoglobin ≥ 10 g/dL (≥ 100 g/L) (red blood cell transfusion is allowed)
• 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 ≥ 3.0 g/dL (≥ 30 g/L)
• Calculated creatinine clearance ≥ 30 mL/min by the CKD-EPI method.
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 3.0 x the upper limit of normal
• Urine protein/creatinine ratio (UPCR) ≤ 1g/g (≤ 113.17 mg/mmol creatinine) or 24-hour urine protein \< 1 g
• Left-ventricular ejection fraction ≥ 50%
• Subjects affiliated to an appropriate social security system

You may not qualify if:

• 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 abdomino and/or pelvic fistula, gastrointestinal perforation, or intra-abdominal abscess, gastro-intestinal obstruction
• Patients with lesions on baseline pelvic MRI which may major the risk of abdominal and/or pelvic fistula/perforation
• 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.
• Previously identified allergy or hypersensitivity to components of the study treatment formulations (Note: patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take cabozantinib and are also excluded).
• 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 surgery, symptomatic peripheral vascular disease, class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA), serious cardiac arrythmias.
• Uncontrolled hypertension defined as systolic blood pressure (SBP) of \> 150 mmHg or diastolic blood pressure (DBP) of \> 100 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 4 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 coagulopathy or tumor involving major vessels.
• At least 6 weeks must have elapsed between the last dose of pelvis palliative radiation and the first dose of cabozantinib or 2 weeks for other localization of palliative radiation
• Concomitant use of known strong CYP3A4 inhibitors or inducers.
• 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
• 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
• Concurrent participation in any therapeutic clinical trial
• Patient deprived of liberty or placed under the authority of a tutor

Sponsors & Collaborators

• Centre Francois Baclesse: lead

Study Sites (8)

Institut de cancérologie de l'Ouest

Angers, France

Location

Centre François Baclesse

Caen, France

Location

Centre Oscar LAMBRET

Lille, France

Location

Centre Léon Bérard

Lyon, France

Location

Institut de Cancérologie de Montpellier

Montpellier, France

Location

Institut de cancérologie de l'Ouest

Nantes, France

Location

Institut CURIE

Saint-Cloud, France

Location

Institut Gustave Roussy

Villejuif, France

Location

Related Publications (1)

• Coquan E, Brachet PE, Licaj I, Leconte A, Castera M, Lequesne J, Meriaux E, Bonnet I, Lelaidier A, Clarisse B, Joly F. CABOCOL-01 trial: a single-arm phase II study assessing safety and efficacy of Cabozantinib for advanced or metastatic cervical carcinoma after platinum treatment failure. BMC Cancer. 2021 Sep 25;21(1):1054. doi: 10.1186/s12885-021-08758-9.

  PMID: 34563169 DERIVED

MeSH Terms

Conditions

Uterine Cervical Neoplasms; Neoplasm Metastasis

Interventions

cabozantinib

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 28, 2019
• First Posted: December 19, 2019
• Study Start: January 15, 2020
• Primary Completion: January 15, 2023
• Study Completion: January 15, 2023
• Last Updated: February 13, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (8)