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

Regorafenib in Combination With Metronomic Cyclophosphamide, Capecitabine, and Low-dose Aspirin in Metastatic Colorectal Cancer Carcinoma An Open-label Phase II

Sponsors

Lead Sponsor: Centre Hospitalier Universitaire de Besancon

Collaborator: Bayer

Source Centre Hospitalier Universitaire de Besancon
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.

Overall Status Not yet recruiting
Start Date September 2020
Completion Date September 2022
Primary Completion Date January 2022
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
objective response rate From date of inclusion until end of treatment for the patient, assessed to 4 months
Enrollment 49
Condition
Intervention

Intervention Type: Drug

Intervention Name: Regorafenib

Description: 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.

Arm Group Label: Experimental

Other Name: Stivarga

Intervention Type: Drug

Intervention Name: Cyclophosphamide

Description: 50 mg per os, daily, for 6 months

Arm Group Label: Experimental

Other Name: Endoxan

Intervention Type: Drug

Intervention Name: Capecitabine

Description: 625mg/m²/orally twice daily continuously until progression

Arm Group Label: Experimental

Other Name: Xeloda

Intervention Type: Drug

Intervention Name: Aspirin

Description: 75 mg orally and daily until progression

Arm Group Label: Experimental

Other Name: Kardegic

Eligibility

Criteria:

Inclusion Criteria: - 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. 1. Haemoglobin ≥ 9 g/dL; absolute neutrophil count (ANC) ≥ 1.5 x 109/L; platelets ≥ 100 x 109/L 2. 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 3. Cockcroft glomerular filtration rate > 50 ml/min 4. 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. - Registration in a national health care system (CMU included). Exclusion criteria: - Diagnosis of additional malignancy within 2 years prior to the inclusion (exception of curatively treated basal cell carcinoma of the skin and/or curatively resected in situ cervical cancer), - Current participation in a study of an investigational agent or in the period of exclusion - 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 inclusion in the trial ; - 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, - Active hepatitis B or C or chronic hepatitis B or C requiring treatment with antiviral therapy, - Subjects with seizure disorder requiring medication, - History of organ allograft, - Subjects with evidence or history of any bleeding diathesis, irrespective of severity, - Any haemorrhage or bleeding event ≥ CTCAE Grade 3 within 4 weeks prior to the start of study medication, - Serious, Non-healing wound, active ulcer or untreated bone fracture, - History of abdominal fistula, GI perforation, intra-abdominal abscess or active GI bleeding within 6 months prior to inclusion, - Dehydration CTCAE v4 grade ≥1, - Known hypersensitivity to any of the study drugs, study drug classes or excipient in the formulation, - Interstitial lung disease with ongoing signs or symptoms, - Persistent proteinuria of CTCAE Grade 3 (>3.5 g/24 hours), - Subject unable to swallow oral medications, - Any malabsorption condition, unresolved toxicity higher than CTCAE (V4) Grade 1 attributed to any prior therapy/procedure excluding alopecia, hypothyroidism and oxaliplatin induced neuropathy ≤ Grade 2, - Systemic anticancer therapy including cytotoxic therapy, signal transduction inhibitors, immunotherapy, and hormonal therapy during this trial or within 3 weeks, - Treatment with any other investigational medicinal product within 28 days prior to study entry, EXCEPT for ASPIRIN, - Co-administration of drugs potentially interacting with regorafenib i.e. CYP3A4 or UGT1A9 inducers/inhibitors.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Marine JARY Principal Investigator CHU Besançon
Overall Contact

Last Name: Marine JARY

Phone: +33381479999

Email: [email protected]

Location
Facility: Contact:
CHU de Besançon | Besançon, 25030, France Marine JARY, Dr +33 3.81.47.99.99 [email protected]
Hôpital Nord Franche-Comté | Montbéliard, France Christophe BORG, Pr
Location Countries

France

Verification Date

July 2020

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Label: Experimental

Type: Experimental

Description: 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 until progression Cyclophosphamide: 50 mg per os, daily, for 6 months ASPIRIN: 75 mg orally and daily until progression

Acronym REPROGRAM-01
Patient Data No
Study Design Info

Allocation: N/A

Intervention Model: Single Group Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov