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Safety, Tolerability and Efficacy of Regorafenib in Combination With FOLFIRINOX in Patients With Colorectal Cancer (FOLFIRINOX-R)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03828799
Recruitment Status : Recruiting
First Posted : February 4, 2019
Last Update Posted : June 9, 2020
Information provided by (Responsible Party):
Institut du Cancer de Montpellier - Val d'Aurelle

Brief Summary:
Safety, tolerability and efficacy of regorafenib in combination with FOLFIRINOX in patients with RAS-mutated metastatic colorectal cancer: a dose-escalation, phase I/II trial

Condition or disease Intervention/treatment Phase
Metastatic Colorectal Cancer Combination Product: Folfirinox + regorrafenib Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 87 participants
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Safety, Tolerability and Efficacy of Regorafenib in Combination With FOLFIRINOX in Patients With RAS-mutated Metastatic Colorectal Cancer: a Dose-escalation, Phase I/II Trial
Actual Study Start Date : May 17, 2019
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : March 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Regorafenib

Arm Intervention/treatment
Experimental: Folfirinox-R
Folfirinox + regorafenib
Combination Product: Folfirinox + regorrafenib
folfirinox : from day 1 to day 3 regorafenib : day 4 to day 10 a cycle during 14 days

Primary Outcome Measures :
  1. Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 [ Time Frame: At the end of cycle 1 to 3 (each cycle is 14 days) ]
    During the first three cycles

Secondary Outcome Measures :
  1. Progression-free survival (PFS) [ Time Frame: Aprroximately 24 months ]
    From baseline of first patient until the datebase cut-off

  2. Disease control rate (DCR) [ Time Frame: Aprroximately 24 months ]
    From baseline of first patient until the datebase cut-off

  3. Objective response rate (ORR) [ Time Frame: Tumor is assessed at 8 weeks intervals ]
    From baseline of first patient until the end of treatment

  4. Deepness of response (DpR) [ Time Frame: Tumor is assessed at 8 weeks intervals ]
    From baseline of first patient until the end of treatment lesions at the nadir, in the absence of new lesions or progression of non-target lesions, as compared to baseline

  5. Time to recurrence under maintenance [ Time Frame: Approximately 10 months ]
    From baseline of first patient until the progression of disease

  6. Overall survival (OS) [ Time Frame: Aprroximately 24 months ]
    From baseline of first patient until the datebase cut-off

  7. Resection (R) rates [ Time Frame: Approximately at 6 months ]
    Through the treatment

  8. Determination of circulating free DNA concentration [ Time Frame: Baseline, 8 weeks, 16 weeks etc. through the end of treatment ]
    From baseline of first patient until the end of treatment

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Written informed consent for full study.
  2. Measurable disease, defined as at least one unidimensional measurable lesion on a CT scan, according to RECIST version 1.1.
  3. ECOG performance status ≤1.
  4. Life expectancy of at least 3 months.
  5. Adequate bone marrow, renal and liver functions as evidenced by the following laboratory requirements within 7 days prior to study treatment initiation: Absolute neutrophil count (ANC) ≥ 1,500/ mm3 without biologic response modifiers such as granulocyte colony-stimulating factor (G-CSF), within 21 days before the start of study treatment, Platelet count ≥ 100 000/mm3 , without platelet transfusion within 21 days before the start of study treatment ,Hemoglobin (Hb) ≥ 9 g/dL, without blood transfusion or erythropoietin, within 21 days before the start of study treatment, Serum creatinine ≤ 1.5 x upper limit of normal(ULN) Serum calcium ≥ LLN and ≤ 1.2 x UNL ; Serum magnesium ≥ LLN and ≤ 1.2 x UNL ; Kalemia ≥ LLN, Glomerular filtration rate as assessed by the estimated glomerular filtration rate (eGFR) ≥ 50 mL/min per 1.73 m2 calculated by the Modification of Diet in Renal Disease (MDRD) abbreviated formula, Total bilirubin ≤ 1.5 x ULN, Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN (≤ 5 x ULN for patients with liver involvement of their cancer), Alkaline phosphatase (ALP) ≤ 2.5 x ULN (≤ 5.0 x ULN for patients with liver involvement for their cancer and/or bone metastases).
  6. Lipase ≤ 1.5 x ULN.
  7. Adequate coagulation, as assessed by the following laboratory test results:

    International normalized ratio (INR) ≤ 1.5 or prothrombin time (PT) ≤ 1.5 x ULN, Partial thromboplastin time (PTT) or activated PTT (aPTT) ≤ 1.5 x ULN, Note: Patients on stable dose (dose has not been changed in at least 28 days) of anticoagulation therapy will be allowed to participate if they have no sign of bleeding or clotting and INR / PT and PTT / aPTT test results are compatible with the acceptable benefit-risk ratio at the investigator's discretion. In such case, limits as noted would not apply.

  8. For women of reproductive potential, negative serum beta human chorionic gonadotropin (β-HCG) pregnancy test obtained within 7 days before the start of study treatment. Women not of reproductive potential are female patients who are postmenopausal or permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy).
  9. For women of childbearing potential and men, agreement to use an adequate contraception for the duration of study participation and up to 4 months following completion of therapy for women and 6 months for male patients. Females of childbearing potential who are sexually active with a non-sterilized male partner must use 2 methods of effective contraception. The investigator or a designated associate is requested to advise the patient on how to achieve an adequate birth control.

    Adequate contraception is defined in the study as any medically recommended method (or combination of methods) as per standard of care.

  10. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
  11. Affiliation to the Social Security System.

Exclusion Criteria:

  1. Previous or concurrent cancer that is distinct in primary site or histology from colorectal cancer within 5 years prior to study inclusion, except for curatively treated cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumors [Ta (noninvasive tumor), Tis (carcinoma in situ) and T1 (lamina propria invasion)].
  2. Discovery of metastases within 6 months after the termination of adjuvant chemotherapy.
  3. Previous treatment for metastatic disease.
  4. Radiotherapy within 28 days prior to first dose of treatment.
  5. Active cardiac disease including any of the following:

    Congestive heart failure New York Heart Association (NYHA) class 2, Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months), Myocardial infarction less than 6 months before first dose of treatment, Cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted).

  6. ECG with a QT/QTc interval higher than 450 ms for men and higher than 470 ms for women Uncontrolled hypertension.
  7. Uncontrolled hypertension. (Systolic blood pressure > 140 mmHg or diastolic pressure > 90 mmHg despite optimal medical management).
  8. Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 6 months before start of treatment.
  9. Persistent proteinuria of National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE V5) grade 3 (i.e. urinary protein ≥ 3.5 g/24 hrs)
  10. Peripheral neuropathy > grade1 (NCI-CTCAE v5).
  11. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to first dose of Treatment.
  12. Ongoing infection >grade 2 (NCI-CTCAE v5).
  13. Known history of human immunodeficiency virus (HIV) infection.
  14. Chronic hepatitis B or C infection (if hepatitis status cannot be obtained from medical records, re-testing is required).
  15. Seizure disorder requiring medication.
  16. Symptomatic metastatic brain or meningeal tumors.
  17. Evidence or history of any bleeding diathesis, irrespective of severity. Any hemorrhage or bleeding event ≥ grade 3 (NCI-CTCAE v5) within 4 weeks prior to the start of study medication.
  18. History of organ allograft.
  19. Non-healing wound, ulcer, or bone fracture.
  20. Dehydration Grade 1 NCI-CTCAE v5).
  21. Substance abuse, medical, psychological, or social conditions that may interfere with the patient's participation in the study or evaluation of the study results.
  22. Known hypersensitivity to any of the study drugs, study drug classes, or any constituent of the products.
  23. Interstitial lung disease with ongoing signs and symptoms.
  24. Concomitant intake of St. John's wort.
  25. Live attenuated vaccines are prohibited 10 days before the treatment, during the treatment and 3 months after the termination of treatment
  26. History of gastrointestinal fistula or perforation
  27. Inability to swallow oral medication.
  28. Any malabsorption condition.
  29. Pregnant or breast-feeding subjects.
  30. Any condition that, in the opinion of the investigator, would interfere with the evaluation of study treatment or interpretation of patient safety or study results.
  31. Participation in another clinical study with an investigational product during the last 30 days before inclusion.
  32. Patients who might be interconnected with or dependent on the sponsor site or the investigator.
  33. Legal incapacity or limited legal capacity.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03828799

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Contact: Jean-Pierre Bleuse, MD 0467613102 ext +33

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Institut du Cancer de Montpellier - Val d'Aurelle Recruiting
Montpellier, France, 34298
Contact: Marc YCHOU, MD, PhD    +33467613102   
Principal Investigator: Marc YCHOU, MD, PhD         
Sponsors and Collaborators
Institut du Cancer de Montpellier - Val d'Aurelle
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Study Chair: Antoine Adenis, MD Institut régional du cancer de Montpellier

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Responsible Party: Institut du Cancer de Montpellier - Val d'Aurelle Identifier: NCT03828799    
Other Study ID Numbers: 2018-003541-42
First Posted: February 4, 2019    Key Record Dates
Last Update Posted: June 9, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Institut du Cancer de Montpellier - Val d'Aurelle:
Metastatic colorectal cancer
Colorectal cancer
RAS mutated
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Antineoplastic Agents