Regorafenib in Combination With Metronomic Chemotherapies, and Low-dose Aspirin in Metastatic Colorectal Cancer

NCT04534218 | Completed Phase 2 DMC

• 1 other identifier: 2020/490
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 3

Brief Summary

The investigators propose a phase II clinical trial with the objective to investigate the potential clinical interest to associate regorafenib with a metronomic chemotherapy combining capecitabine, cyclophosphamide and low-dose aspirin, for the treatment of patients with metastatic colorectal cancer. The main objective of the study will be to achieve 15% of objective response rate in patients treated with multimodal metronomic chemotherapy and regorafenib.

Conditions

Colo-rectal Cancer; Metastatic Cancer

Keywords

regorafenib; metronomic chemotherapy; colon cancer

Outcome Measures

Primary Outcomes (1)

• objective response rate

  The objective response rate (ORR) will be defined by RECIST v1.1 criteria as the best disease response observed during the treatment period (assessed to 4 months). ORR rate is defined as the proportion of patients whose tumor regresses or does not progress under treatment.

  From date of inclusion until end of treatment for the patient, assessed to 4 months

Study Arms (1)

Experimental

EXPERIMENTAL

REGORAFENIB: * For the first cycle: regorafenib will be administered according to the "REDOS" schedule (80 mg daily for week 1, 120 mg daily for week 2 and 160 mg daily for the third week of the first cycle). * For the following cycles: regorafenib will be administered at a 80, 120 or 160 mg daily dose according to toxicity observed with the last dose used in the first cycle. METRONOMIC CHEMOTHERAPIES: * Capecitabine: 625mg/m²/orally twice daily continuously for 6 months * Cyclophosphamide: 50 mg per os, daily, for 6 months ASPIRIN: 75 mg orally and daily until progression

Drug: Regorafenib; Drug: Cyclophosphamide; Drug: Capecitabine; Drug: Aspirin

Interventions

Regorafenib DRUG

* For the first cycle: regorafenib will be administered according to the "REDOS" schedule (80 mg daily for week 1, 120 mg daily for week 2 and 160 mg daily for the third week of the first cycle). * For the following cycles: regorafenib will be administered at a 80, 120 or 160 mg daily dose according to toxicity observed with the last dose used in the first cycle.

Also known as: Stivarga

Experimental

Cyclophosphamide DRUG

50 mg per os, daily, for 6 months

Also known as: Endoxan

Experimental

Capecitabine DRUG

625mg/m²/orally twice daily continuously for 6 months

Also known as: Xeloda

Experimental

Aspirin DRUG

75 mg orally and daily until progression

Also known as: Kardegic

Experimental

Eligibility Criteria

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

You may qualify if:

• Patients with histologically proven metastatic colorectal cancer in progression after previous standard treatments (5FU, CPT11, oxaliplatin, anti-VEGF and anti-EGFR therapy if KRAS and NRAS WT), or not considered as candidate for these treatments
• Life expectancy of at least 3 months
• Female or male with age \>18 years old
• Performance status = 0 or 1 (Annex 1)
• Measurable disease defined according to RECIST v1.1 (scanner or MRI) (Annex 2)
• Adequate bone marrow, liver and renal functions.
• Haemoglobin ≥ 9 g/dL; absolute neutrophil count (ANC) ≥ 1.5 x 109/L; platelets ≥ 100 x 109/L
• Total serum bilirubin ≤ 1.5 times upper normal value (ULN), serum alkaline phosphatase \< 5 times ULN, aminotransferases (AST/ALT) ≤ 3 × ULN in absence of hepatic metastasis or ≤ 5 if presence of hepatic lesions
• Cockcroft glomerular filtration rate \> 50 ml/min
• Proteinuria \<2+ (dipstick urinalysis) or ≤1g/24hour
• Imaging target greater than one cm must be visible on CT,
• No contraindication to Iodine contrast media injection during CT
• For female patients of childbearing potential, negative pregnancy test within 14 days before starting the study drug. Men and women are required to use adequate birth control during the study (when applicable),
• Signed and dated informed consent,
• Ability to comply with the study protocol, in the Investigator's judgment.

You may not qualify if:

• Patient under judicial protection (curatorship, tutorship) and/or deprived of freedom,
• Planned surgical procedure within the first month of treatment or any procedure that might change the timing of regorafenib administration during the first month of treatment,
• Previous exposure to regorafenib,
• Previous exposure to other anti-angiogenic treatment than bevacizumab and aflibercept,
• Complete deficit in dihydropyrimidine deshydrogenase (DPD),
• Major surgical procedure, open biopsy or significant traumatic injury within 28 days before start of study medication,
• Pregnant or breast-feeding subjects,
• Congestive Heart Failure ≥ New York Heart Association (NYHA) class 2, unstable angina (anginal symptomatology at rest),
• Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months),
• Myocardial infarction less than 6 months before start of study drug,
• Cardiac arrhythmias requiring anti-arrhythmic therapy (beta-blockers or digoxin are permitted),
• Uncontrolled hypertension (Systolic blood pressure \>150 mmHg and/or diastolic pressure \>100 mmHg despite optimal medical management), or history of hypertensive crisis, or hypertensive encephalopathy
• Pleural effusion or ascites that causes respiratory compromise (≥ CTCAE grade 2 dyspnea),
• Ongoing infection \>grade 2 CTCAE V5,
• Known History of human immunodeficiency virus (HIV) infection,

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Besancon: lead
• Bayer: collaborator

Study Sites (3)

CHU de Besançon

Besançon, 25030, France

Location

Centre georges-François Leclerc

Dijon, 21000, France

Location

Hôpital Nord Franche-Comté

Montbéliard, France

Location

MeSH Terms

Conditions

Colonic Neoplasms; Neoplasm Metastasis

Interventions

regorafenib; Cyclophosphamide; Capecitabine; Aspirin

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; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic

Study Officials

• christophe.borg@efs.sante.fr BORG, Pr

  CHU Besançon

  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: SPONSOR

Study Record Dates

• First Submitted: July 16, 2020
• First Posted: September 1, 2020
• Study Start: October 16, 2020
• Primary Completion: December 13, 2023
• Study Completion: December 13, 2023
• Last Updated: December 20, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

FR (3)