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Regorafenib Assessment in Refractory Advanced Colorectal Cancer(RegARd-C) (RegARd-C)

Primary Purpose

Advanced Chemorefractory Colorectal Adenocarcinoma

Status
Completed
Phase
Phase 2
Locations
Belgium
Study Type
Interventional
Intervention
regorafenib
Sponsored by
Jules Bordet Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Chemorefractory Colorectal Adenocarcinoma focused on measuring adenocarcinoma, colorectal,regorafenib

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Histologically proven colorectal adenocarcinoma that is metastatic or unresectable and for which standard treatments do not exist or are no longer effective.
  2. Age ≥ 18 years.
  3. Life expectancy of greater than 12 weeks.
  4. ECOG performance status ≤ 1.

  5. Participants must have normal organ and bone marrow function as defined below:

    • Leukocytes >3,000/mcL,with an absolute neutrophil count >1,500/mcL, platelets >100,000/mcL, Hb >or=9g/dl.
    • Total bilirubin≤1.5×institutional ULN.
    • AST/ALT/P-Alk levels ≤ 2.5 × institutional ULN (≤5x institutional ULN in case of liver metastatic involvement).
    • Lipase ≤1.5 institutional ULN.
    • coagulation tests ≤ 1.5 x institutional ULN.
    • Creatinine ≤ 1.5× institutional ULN or creatinine clearance >30mL/min according to the Modified Diet in Renal Disease (MDRD) abbreviated formula.
  6. Women of childbearing potential and men must agree to use adequate contraception prior to study entry, until at least 3 months after the last study drug administration.
  7. Signed Written Informed Consent (IC).
  8. Presence of a previously collected or freshly obtained at the time of study entry frozen metastatic tumor biopsy in a FDG-PET targetable lesion.
  9. Presence of at least one metabolically measurable tumoral lesion on FDG PET-CT

Exclusion Criteria:

  1. Prior treatment with sorafenib or regorafenib
  2. Patients with previous cancer that is not disease-free for at least for 5 years prior to registration, EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumors [Ta (Non-invasive tumor), Tis (Carcinoma in situ) and T1 (Tumor invades lamina propria)].
  3. Participants who have had a major surgery, chemotherapy or radiotherapy within 4 weeks prior to entering the study.
  4. Unresolved toxicity higher than NCI-CTCAE (version 4.0) Grade 1 attributed to any prior therapy/procedure excluding alopecia and oxaliplatin induced neurotoxicity ≤Grade 2.
  5. Participants receiving any experimental agents.
  6. Participants with known brain metastases.
  7. Bleeding diathesis, history of cardiovascular ischemic disease or cerebrovascular incident within the last six months.
  8. Any hemorrhage or bleeding event NCI-CTCAE v.4 Grade >or= 3 within 4 weeks prior to the start of study medication.
  9. Uncontrolled concurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure (New York Heart Association (NYHA)class> or=2), unstable angina pectoris, cardiac arrhythmia requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted).
  10. Uncontrolled hypertension.
  11. Patients with seizure disorder requiring medication.
  12. Any history of organ allograft.
  13. Pleural effusion or ascites affecting respiration.
  14. Uncontrolled diabetes.
  15. Non-healing wound, ulcer, or bone fracture.
  16. Known history of human immunodeficiency virus (HIV) infection, or active hepatitis B or C, or chronic hepatitis B or C requiring treatment with antiviral therapy.
  17. Interstitial lung disease with ongoing signs and symptoms.
  18. Renal failure requiring hemo-or peritoneal dialysis.
  19. Dehydration NCI-CTCAE v.4 grade >1.
  20. Medical,psychological or social conditions that may interfere with the patient's ability to understand informed consent and participation in the study or evaluation of the study results.
  21. Known hypersensitivity to the study drug or excipients in the formulation.
  22. Any illness or medical conditions that are unstable or could jeopardize the safety of the patient and his/her compliance in the study.
  23. Pregnant or lactating women.
  24. Subjects unable to swallow oral medications.

Sites / Locations

  • UZA
  • Jules Bordet Institute
  • Hopital Erasme
  • Cliniques Universitaires Saint Luc
  • Grand Hopital de Charleroi
  • UZ Ghent
  • AZ groeninge
  • Centre Hospitalier Universitaire de Liège
  • Clinique St Joseph
  • Centre hospitalier de Jolimont
  • CHU Ambroise Paré
  • Centre Hospitalier Régional de Namur
  • Clinique et Maternité Sainte Elisabeth
  • Clinique Saint Pierre
  • Hartziekenhuis Roeselare-Menen (HHRM)
  • AZ Turnhout
  • Cliniques Universitaires UCL de Mont-Godinne

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Regorafenib

Arm Description

A treatment cycle is defined as a 4 weeks period. Regorafenib will be administered once a day orally at a dose of 160 mg (4 tablets of 40 mg), for 3 weeks.

Outcomes

Primary Outcome Measures

Overall survival (OS)

Secondary Outcome Measures

Occurence of Adverse events
Assessment of safety will follow the WHO guidelines and classified according to NCI-CTCAE v. 4.0 and will be performed every 28 days until 28 days (safety follow up visit) after stopping therapy. Reasons for stopping therapy may include progression of disease or unbearable toxicities, or patient's decision.
Evaluation of tumour response
RECIST 1.1-based radiological assessment (CT or MRI) will be made every 2 cycles, starting at day 28 of the second cycle till demonstration of progressive disease. An average of 2 months is expected.
Metabolic response assessed by FDG PET
FDGPET will be done twice during the study course : at baseline (at day 0, before treatment begin) and after 2 weeks.
Molecular aberrations
Genetic, epigenetic and molecular aberrations will be investigated using gene expression profiling, RNA and exome sequencing, and methylation profiling on the tumor biopsies and repeated blood samples collected during the trial. The relationship between the molecular aberrations,the patient's outcome (PFS, OS) and with metabolic response after treatment with regorafenib will be studied.

Full Information

First Posted
July 28, 2013
Last Updated
June 21, 2019
Sponsor
Jules Bordet Institute
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1. Study Identification

Unique Protocol Identification Number
NCT01929616
Brief Title
Regorafenib Assessment in Refractory Advanced Colorectal Cancer(RegARd-C)
Acronym
RegARd-C
Official Title
Regorafenib Assessment in Refractory Advanced Colorectal Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
March 2017
Overall Recruitment Status
Completed
Study Start Date
August 2013 (undefined)
Primary Completion Date
May 13, 2016 (Actual)
Study Completion Date
June 17, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Jules Bordet Institute

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The general objectives are to evaluate activity and the safety of regorafenib in a population of patients bearing advanced, refractory colorectal cancers and to explore the different downstream molecular pathways to identify tumor response and resistance mechanisms.
Detailed Description
The primary objective is to identify in a population of patients bearing advanced, refractory colorectal cancers, those who draw no benefit from treatment with regorafenib. There is no specific hypothesis underlying sample size and the study is therefore to be seen as exploratory. Secondary objectives: To analyze PFS and response rate (RR) in relationship with the same covariates as for OS To assess regorafenib efficacy (OS, PFS, RR) and safety profile in this study population. To assess the Disease control rate (DCR = Complete response [CR] + partial response [PR] + stable disease [SD]) To compare the relative benefit (OS, PFS) of regorafenib according to history of treatment with bevacizumab.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Chemorefractory Colorectal Adenocarcinoma
Keywords
adenocarcinoma, colorectal,regorafenib

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
141 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Regorafenib
Arm Type
Experimental
Arm Description
A treatment cycle is defined as a 4 weeks period. Regorafenib will be administered once a day orally at a dose of 160 mg (4 tablets of 40 mg), for 3 weeks.
Intervention Type
Drug
Intervention Name(s)
regorafenib
Other Intervention Name(s)
stivarga (registred name)
Intervention Description
Patients will receive 160 mg regorafenib 1/day 3 weeks out of 4.
Primary Outcome Measure Information:
Title
Overall survival (OS)
Time Frame
2 years from first patient in
Secondary Outcome Measure Information:
Title
Occurence of Adverse events
Description
Assessment of safety will follow the WHO guidelines and classified according to NCI-CTCAE v. 4.0 and will be performed every 28 days until 28 days (safety follow up visit) after stopping therapy. Reasons for stopping therapy may include progression of disease or unbearable toxicities, or patient's decision.
Time Frame
Every 28 days till 28 days after stopping therapy. An average of 2 months is expected.
Title
Evaluation of tumour response
Description
RECIST 1.1-based radiological assessment (CT or MRI) will be made every 2 cycles, starting at day 28 of the second cycle till demonstration of progressive disease. An average of 2 months is expected.
Time Frame
Every 2 months till progression of the disease. An average of 2 months is expected.
Title
Metabolic response assessed by FDG PET
Description
FDGPET will be done twice during the study course : at baseline (at day 0, before treatment begin) and after 2 weeks.
Time Frame
2 FDGPET will be perfomed : at Baseline (day 0) and at D14
Title
Molecular aberrations
Description
Genetic, epigenetic and molecular aberrations will be investigated using gene expression profiling, RNA and exome sequencing, and methylation profiling on the tumor biopsies and repeated blood samples collected during the trial. The relationship between the molecular aberrations,the patient's outcome (PFS, OS) and with metabolic response after treatment with regorafenib will be studied.
Time Frame
at day 0 (before treatment begins) and at D14, then repeated every 2 months until progression. An average of 2 months is expected.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically proven colorectal adenocarcinoma that is metastatic or unresectable and for which standard treatments do not exist or are no longer effective. Age ≥ 18 years. Life expectancy of greater than 12 weeks. ECOG performance status ≤ 1. Participants must have normal organ and bone marrow function as defined below: Leukocytes >3,000/mcL,with an absolute neutrophil count >1,500/mcL, platelets >100,000/mcL, Hb >or=9g/dl. Total bilirubin≤1.5×institutional ULN. AST/ALT/P-Alk levels ≤ 2.5 × institutional ULN (≤5x institutional ULN in case of liver metastatic involvement). Lipase ≤1.5 institutional ULN. coagulation tests ≤ 1.5 x institutional ULN. Creatinine ≤ 1.5× institutional ULN or creatinine clearance >30mL/min according to the Modified Diet in Renal Disease (MDRD) abbreviated formula. Women of childbearing potential and men must agree to use adequate contraception prior to study entry, until at least 3 months after the last study drug administration. Signed Written Informed Consent (IC). Presence of a previously collected or freshly obtained at the time of study entry frozen metastatic tumor biopsy in a FDG-PET targetable lesion. Presence of at least one metabolically measurable tumoral lesion on FDG PET-CT Exclusion Criteria: Prior treatment with sorafenib or regorafenib Patients with previous cancer that is not disease-free for at least for 5 years prior to registration, EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumors [Ta (Non-invasive tumor), Tis (Carcinoma in situ) and T1 (Tumor invades lamina propria)]. Participants who have had a major surgery, chemotherapy or radiotherapy within 4 weeks prior to entering the study. Unresolved toxicity higher than NCI-CTCAE (version 4.0) Grade 1 attributed to any prior therapy/procedure excluding alopecia and oxaliplatin induced neurotoxicity ≤Grade 2. Participants receiving any experimental agents. Participants with known brain metastases. Bleeding diathesis, history of cardiovascular ischemic disease or cerebrovascular incident within the last six months. Any hemorrhage or bleeding event NCI-CTCAE v.4 Grade >or= 3 within 4 weeks prior to the start of study medication. Uncontrolled concurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure (New York Heart Association (NYHA)class> or=2), unstable angina pectoris, cardiac arrhythmia requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted). Uncontrolled hypertension. Patients with seizure disorder requiring medication. Any history of organ allograft. Pleural effusion or ascites affecting respiration. Uncontrolled diabetes. Non-healing wound, ulcer, or bone fracture. Known history of human immunodeficiency virus (HIV) infection, or active hepatitis B or C, or chronic hepatitis B or C requiring treatment with antiviral therapy. Interstitial lung disease with ongoing signs and symptoms. Renal failure requiring hemo-or peritoneal dialysis. Dehydration NCI-CTCAE v.4 grade >1. Medical,psychological or social conditions that may interfere with the patient's ability to understand informed consent and participation in the study or evaluation of the study results. Known hypersensitivity to the study drug or excipients in the formulation. Any illness or medical conditions that are unstable or could jeopardize the safety of the patient and his/her compliance in the study. Pregnant or lactating women. Subjects unable to swallow oral medications.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alain Hendlisz, MD
Organizational Affiliation
Jules Bordet Institute
Official's Role
Study Chair
Facility Information:
Facility Name
UZA
City
Antwerpen
State/Province
Edegem
ZIP/Postal Code
2650
Country
Belgium
Facility Name
Jules Bordet Institute
City
Brussels
ZIP/Postal Code
1000
Country
Belgium
Facility Name
Hopital Erasme
City
Brussels
ZIP/Postal Code
1070
Country
Belgium
Facility Name
Cliniques Universitaires Saint Luc
City
Brussels
Country
Belgium
Facility Name
Grand Hopital de Charleroi
City
Charleroi
ZIP/Postal Code
6000
Country
Belgium
Facility Name
UZ Ghent
City
Ghent
Country
Belgium
Facility Name
AZ groeninge
City
Kortrijk
ZIP/Postal Code
8500
Country
Belgium
Facility Name
Centre Hospitalier Universitaire de Liège
City
Liège
ZIP/Postal Code
4000
Country
Belgium
Facility Name
Clinique St Joseph
City
Liège
ZIP/Postal Code
4000
Country
Belgium
Facility Name
Centre hospitalier de Jolimont
City
Lobbes
ZIP/Postal Code
6540
Country
Belgium
Facility Name
CHU Ambroise Paré
City
Mons
ZIP/Postal Code
7000
Country
Belgium
Facility Name
Centre Hospitalier Régional de Namur
City
Namur
ZIP/Postal Code
5000
Country
Belgium
Facility Name
Clinique et Maternité Sainte Elisabeth
City
Namur
ZIP/Postal Code
5000
Country
Belgium
Facility Name
Clinique Saint Pierre
City
Ottignies
ZIP/Postal Code
1340
Country
Belgium
Facility Name
Hartziekenhuis Roeselare-Menen (HHRM)
City
Roeselare
ZIP/Postal Code
8800
Country
Belgium
Facility Name
AZ Turnhout
City
Turnhout
ZIP/Postal Code
2300
Country
Belgium
Facility Name
Cliniques Universitaires UCL de Mont-Godinne
City
Yvoir
ZIP/Postal Code
5530
Country
Belgium

12. IPD Sharing Statement

Citations:
PubMed Identifier
30744591
Citation
Charette N, Vandeputte C, Ameye L, Bogaert CV, Krygier J, Guiot T, Deleporte A, Delaunoit T, Geboes K, Van Laethem JL, Peeters M, Demolin G, Holbrechts S, Flamen P, Paesmans M, Hendlisz A. Prognostic value of adipose tissue and muscle mass in advanced colorectal cancer: a post hoc analysis of two non-randomized phase II trials. BMC Cancer. 2019 Feb 12;19(1):134. doi: 10.1186/s12885-019-5319-8.
Results Reference
derived
PubMed Identifier
25753361
Citation
Hendlisz A, Deleporte A, Vandeputte C, Charette N, Paesmans M, Guiot T, Garcia C, Flamen P. Regorafenib assessment in refractory advanced colorectal cancer: RegARd-C study protocol. BMJ Open. 2015 Mar 9;5(3):e007189. doi: 10.1136/bmjopen-2014-007189.
Results Reference
derived

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Regorafenib Assessment in Refractory Advanced Colorectal Cancer(RegARd-C)

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