Clinical trial NCT01929616: Regorafenib Assessment in Refractory Advanced Colorectal Cancer(RegARd-C)
Official title: Regorafenib Assessment in Refractory Advanced Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Advanced Chemorefractory Colorectal Adenocarcinoma
Keywords: adenocarcinoma, colorectal,regorafenib
Lead sponsor: Jules Bordet Institute
Sponsor class: OTHER
First posted: 2013-08-28
Enrollment: 141
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Overall survival (OS)
timeFrame: 2 years from first patient in
Secondary outcomes:
measure: Occurence of Adverse events
timeFrame: Every 28 days till 28 days after stopping therapy. An average of 2 months is expected.
measure: Evaluation of tumour response
timeFrame: Every 2 months till progression of the disease. An average of 2 months is expected.
measure: Metabolic response assessed by FDG PET
timeFrame: 2 FDGPET will be perfomed : at Baseline (day 0) and at D14
measure: Molecular aberrations
timeFrame: at day 0 (before treatment begins) and at D14, then repeated every 2 months until progression. An average of 2 months is expected.
Other outcomes:
Locations:
city: Antwerpen
country: Belgium
facility: UZA
state: Edegem
city: Brussels
country: Belgium
facility: Jules Bordet Institute
city: Brussels
country: Belgium
facility: Hopital Erasme
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint Luc
city: Charleroi
country: Belgium
facility: Grand Hopital de Charleroi
city: Ghent
country: Belgium
facility: UZ Ghent
city: Kortrijk
country: Belgium
facility: AZ groeninge
city: Liège
country: Belgium
facility: Centre Hospitalier Universitaire de Liège
city: Liège
country: Belgium
facility: Clinique St Joseph
city: Lobbes
country: Belgium
facility: Centre hospitalier de Jolimont
city: Mons
country: Belgium
facility: CHU Ambroise Paré
city: Namur
country: Belgium
facility: Centre Hospitalier Régional de Namur
city: Namur
country: Belgium
facility: Clinique et Maternité Sainte Elisabeth
city: Ottignies
country: Belgium
facility: Clinique Saint Pierre
city: Roeselare
country: Belgium
facility: Hartziekenhuis Roeselare-Menen (HHRM)
city: Turnhout
country: Belgium
facility: AZ Turnhout
city: Yvoir
country: Belgium
facility: Cliniques Universitaires UCL de Mont-Godinne
Study officials:
affiliation: Jules Bordet Institute
name: Alain Hendlisz, MD
role: STUDY_CHAIR
References:
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.
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.