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

• ClinicalTrials.gov Identifier: NCT01929616
• Recruitment Status: Completed
• First Posted: August 28, 2013
• Last Update Posted: June 25, 2019
• Sponsor: Jules Bordet Institute
• Information provided by (Responsible Party): Jules Bordet Institute

Tracking Information

• First Submitted Date: July 28, 2013
• First Posted Date: August 28, 2013
• Last Update Posted Date: June 25, 2019
• Study Start Date: August 2013
• Actual Primary Completion Date: May 13, 2016 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: August 21, 2013): Overall survival (OS) [ Time Frame: 2 years from first patient in ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 21, 2013)

• Occurence of Adverse events [ Time Frame: Every 28 days till 28 days after stopping therapy. An average of 2 months is expected. ]
  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 [ Time Frame: Every 2 months till progression of the disease. An average of 2 months is expected. ]
  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 [ Time Frame: 2 FDGPET will be perfomed : at Baseline (day 0) and at D14 ]
  FDGPET will be done twice during the study course : at baseline (at day 0, before treatment begin) and after 2 weeks.
• Molecular aberrations [ 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. ]
  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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Regorafenib Assessment in Refractory Advanced Colorectal Cancer(RegARd-C)
• Official Title: Regorafenib Assessment in Refractory Advanced Colorectal Cancer
• 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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Advanced Chemorefractory Colorectal Adenocarcinoma

Intervention

Drug: regorafenib

Patients will receive 160 mg regorafenib 1/day 3 weeks out of 4.

Other Name: stivarga (registred name)

Study Arms

Experimental: Regorafenib

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: Drug: regorafenib

Publications *

• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 21, 2019): 141
• Original Estimated Enrollment (submitted: August 21, 2013): 124
• Actual Study Completion Date: June 17, 2019
• Actual Primary Completion Date: May 13, 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium

Administrative Information

• NCT Number: NCT01929616
• Other Study ID Numbers: 2012-005655-16 EUDRACT
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Jules Bordet Institute
• Original Responsible Party: Same as current
• Current Study Sponsor: Jules Bordet Institute
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Alain Hendlisz, MD; Jules Bordet Institute

• PRS Account: Jules Bordet Institute
• Verification Date: March 2017