caBozantinib in Pre-treated pAtients With Metastatic COlorectal Cancer.

NCT06171854 | Unknown Phase 2

• 1 other identifier: DMP-001
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase II non-randomised and non-comparative study, in pretreated mCRC patients, progressed after at least 2 lines of prior chemotherapy for metastatic disease. Treatment plan:

• First Stage: A total of 22 patients will be enrolled in the first stage to detect at least 3 patients free of progression at 16 weeks
• Second Stage: If at least 3 patients will be free of progression at 16 weeks, an additional cohort of 11 patients will be enrolled in the second stage

Conditions

Refractory Colorectal Adenocarcinoma

Keywords

crc

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS)

  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.

  16 weeks

Secondary Outcomes (5)

• Progression Free survival (PFS)

  from the start of the study treatment until disease progression or death for any cause, assessed up to 100 months

• Overall Survival (OS)

  from the start of the study treatment until death for any cause, assessed up to 100 months

• Response Rate

  rate of patients with complete response or partial response, as best response, through study completion, an average of 1 year

• Disease Control Rate (DCR)

  rate of patients with complete response, partial response and stable disease, as best response, during the course of the study, average time one year

• Safety as the description of adverse events

  through study completion, an average of 1 year

Study Arms (1)

cabozantinib

EXPERIMENTAL

60 mg once daily. Route: per os Cycle: 28 days

Drug: Cabozantinib

Interventions

Cabozantinib DRUG

cabozantinib in patients with refractory mCRC

Also known as: Cabometyx

cabozantinib

Eligibility Criteria

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

You may qualify if:

• 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.
• \. 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.
• \. 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.
• \. Measurable disease according to RECIST criteria v1.1. 8. ECOG Performance Status 0-1. 9. Life expectancy of at least 3 months. 10. Adequate organ and marrow function, based upon meeting all of the following laboratory criteria within 10 days before study entry:
• Absolute neutrophil count (ANC) ≥ 1500/mm3 (≥ 1.5 GI/L).
• Platelets ≥ 100,000/mm3 (≥ 100 GI/L).
• Hemoglobin ≥ 9 g/dL.
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 3.0 × upper limit of normal.
• Total bilirubin ≤ 1.5 × the upper limit of normal. For subjects with Gilbert's disease ≤ 3 mg/dL.
• Fasting serum triglycerides ≤ 2.5 × upper limit of normal and total cholesterol ≤ 300 mg/dL.
• Note: Lipid-lowering medication is allowed.
• HbA1c ≤ 8%.
• Serum creatinine ≤ 2.0 × upper limit of normal or calculated creatinine clearance ≥ 30 mL/min (≥ 0.5 mL/sec) using the Cockroft-Gault equation.
• hour urine protein \< 1 g. 11. In the investigator judgement, compliance with the protocol requirements and signed informed consent document. 12. Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (e.g., barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 4 months after the last dose of study treatment.
• \. Female subjects of childbearing potential must not be pregnant at screening. Females of childbearing potential are defined as premenopausal females capable of becoming pregnant (i.e. females who have had any evidence of menses in the past 12 months, with the exception of those who had prior hysterectomy). However, women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, low body weight, ovarian suppression or other reasons.

You may not qualify if:

• 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.
• \. 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.
• \. Concomitant anticoagulation at therapeutic doses with oral anticoagulants (e.g., warfarin, direct thrombin and Factor Xa inhibitors) or platelet inhibitors (e.g., clopidogrel).
• Note: Low-dose aspirin for cardioprotection (per local applicable guidelines), low-dose warfarin (\<1 mg/day), and low dose, low molecular weight heparins (LMWH) are permitted. Anticoagulation with therapeutic doses of LMWH is allowed in subjects without radiographic evidence of brain metastasis, who are on a stable dose of LMWH for at least 12 weeks before study entry, and who have had no complications from a thromboembolic event or the anticoagulation regimen.
• \. Chronic treatment with corticosteroids or other immunosuppressive agents (with the exception of inhaled or topical corticosteroids or corticosteroids with a daily dosage equivalent ≤ 10 mg prednisone). Subjects with brain metastases requiring systemic corticosteroid are not eligible.
• \. The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• Cardiovascular disorders:
• Symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmias.
• Uncontrolled hypertension defined as sustained BP \> 150 mm Hg systolic or \> 100 mm Hg diastolic despite optimal antihypertensive treatment.
• Stroke (including TIA), myocardial infarction, or other ischemic event, or thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 6 months before study entry.
• Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation:
• Active peptic ulcer disease, inflammatory bowel disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis or acute obstruction of the pancreatic or biliary duct, or gastric outlet obstruction.
• Abdominal fistula, gastrointestinal perforation, bowel obstruction, or intra-abdominal abscess within 6 months before study entry. Note: Complete healing of an intra-abdominal abscess must be confirmed before study entry.
• Clinically significant hematuria, hematemesis, or hemoptysis of \> 0.5 teaspoon (2.5 ml) of redblood, or other history of significant bleeding (eg, pulmonary hemorrhage) within 3 months before study entry.
• Cavitating pulmonary lesion(s) or known endobronchial disease manifestation.

Sponsors & Collaborators

• University of Campania Luigi Vanvitelli: lead

Study Sites (1)

A.O.U dell'Università degli Studi della Campania "Luigi Vanvitelli"

Napoli, Italy

Location

MeSH Terms

Conditions

Colonic Neoplasms

Interventions

cabozantinib

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases

Study Officials

• Erika Martinelli, MD, PhD

  erika.martinelli@unicampania.it

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 26, 2023
• First Posted: December 15, 2023
• Study Start: September 1, 2019
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: January 2, 2024

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)