A phase II trial with cabozantinib in patients with metastatic colorectal cancer, after previous treatment (mCRC).

Phase 1

• Conditions: Patients with mCRC progressed after =2 lines of standard treatment; MedDRA version: 21.1Level: PTClassification code 10053548Term: Gastrointestinal cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-000674-28-IT
• Lead Sponsor: Dipartimento di Medicina di Precisione - Università degli studi della Campania L. Vanvitelli

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-05-24
• Last Update Posted: 30 August 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 33

Inclusion Criteria

1. Histologically proven diagnosis of colorectal adenocarcinoma.
2. Male or female patients = 18 years of age.
3. Diagnosis of metastatic disease.
4. Known RAS status (NRAS and KRAS exon 2,3 and 4) per local
laboratory assessment.
5. Patients should have received at least two standard lines of treatment including all the following: fluoropyrimidines, irinotecan, oxaliplatin, anti-angiogenic drugs (eg. bevacizumab and or aflibercept) and, in case of patients harbouring RAS WT tumours, anti-Epidermal Growth Factor receptors monoclonal antibodies (cetuximab or panitumumab). Note:
Prior treatment with trifluridine-tipiracil is allowed.
6. Recovery to baseline or = Grade 1 CTCAE v.5.0 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy.
7. Measurable disease according to RECIST criteria v1.1.
8. ECOG Performance Status 0-1.
9. Life expectancy of at least 3 months.
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 33
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 33

Exclusion Criteria

1. Prior treatment with cabozantinib.
2. Prior treatment with VEGFR-targeting TKI (e.g. regorafenib).
3. Treatment with any anticancer drug within 4 weeks before study entry.
4. Radiation therapy for bone metastasis within 2 weeks, any other external radiation therapy within 4 weeks before study entry. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
5. Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 3 months before study entry. Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of study entry.

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine the anti-tumour activity of cabozantinib (evaluated as the number of patients that are free of progression at 16 weeks since the start of treatment) in chemorefractory patients with mCRC, after progression from =2 lines of treatment.;Secondary Objective: To explore the efficacy and the safety of cabozantinib in chemorefractory patients with mCRC, after progression from =2 lines of treatment.;Primary end point(s): Progression Free Survival (PFS) rate at 16 weeks: the rate of patients who have not experienced disease progression or death for any cause at 16 weeks.;Timepoint(s) of evaluation of this end point: Tumour assessments every 8 weeks

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Progression Free survival (PFS): calculated from the start of the study treatment until disease progression or death for any cause.<br>Overall Survival (OS): calculated from the start of the study treatment until death for any cause.<br>Response Rate (RR): assessed according to RECIST criteria 1.1, as the rate of patients with complete response or partial response, as best response.<br>Disease Control Rate (DCR): assessed according to RECIST criteria 1.1, as the rate of patients with complete response, partial response and stable disease, as best response.<br>Safety: Adverse events graded according Events (CTCAE) Version 5.0;Timepoint(s) of evaluation of this end point: Tumour assessments every 8 weeks.<br>Safety will be assessed every 2 weeks up to Week 9 Day 1, and every 4 weeks thereafter.