Regorafenib Versus Placebo to Treat Cholangiocarcinoma

NCT02162914 | Unknown Phase 2

• 1 other identifier: 2012-005626-30
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 12

Brief Summary

The study is a multicenter randomized (1:1) placebo-controlled, double-blinded phase II trial aiming to demonstrate an improvement of median PFS when treating locally advanced unresectable or metastatic patients suffering from an intra-hepatic or hilum (mass-forming) cholangiocarcinoma with Regorafenib as compared to placebo, and after progression after GEM-CDDP (or GEM-OX), or gemcitabine alone followed or preceded by platinum (CDDP or oxaliplatin)-based chemotherapy. The principal objective is to investigate Regorafenib efficacy by prospectively evaluating the PFS after the administration of Regorafenib combined with BSC as compared to placebo with BSC. Hypothesis is a 50% improvement in median PFS (from 6 weeks to 12 weeks in Regorafenib group).

Conditions

Cholangiocarcinoma

Keywords

Intra-hepatic; Hilar; Locally Advanced; Non Resectable; Metastatic; Regorafenib; Placebo

Outcome Measures

Primary Outcomes (1)

• Improve median PFS

  The primary endpoint is to improve median PFS from 6 weeks to 12 weeks in Regorafenib group.

  6 to 12 weeks

Secondary Outcomes (5)

• Evaluation of response rate

  At pretreatment visit (14 to 1 days before treatment initiation), every 6 weeks for 3 times then every 8 weeks until progression

• Correlation between radiological response and metabolic response

  At pretreatment visit (14 to 1 days before treatment initiation)

• Correlation between radiologic response rate and "Dynamic tumor response rate"

  At day 1 (pre-treatment) and day 15 of cycle 1

• Correlation between dynamic tumor response rate and metabolic response rate

  At cycle 1 day 15

• Evaluation of Overall Survival (OS)

  After 1 year (March 2015)

Study Arms (2)

Regorafenib/active

ACTIVE COMPARATOR

Subjects randomized to be treated with Regorafenib (active product) will receive once a day 160 mg po (four tablets of 40 mg) for 3 weeks of every 4 weeks cycle (3 weeks on and 1 week off). Duration of one cycle is 28 days.

Drug: Regorafenib/active

Regorafenib/placebo

PLACEBO COMPARATOR

Subjects randomized to be treated with Regorafenib (placebo) will receive once a day 160 mg po (four tablets of 40 mg) for 3 weeks of every 4 weeks cycle (3 weeks on and 1 week off). Duration of one cycle is 28 days.

Drug: Regorafenib/placebo

Interventions

Regorafenib/active DRUG

Subjects randomized to be treated with Regorafenib/active will receive once a day 160 mg po (four tablets of 40 mg) for 3 weeks of every 4 weeks cycle (3 weeks on and 1 week off) Duration of one cycle is 28 days

Regorafenib/active

Regorafenib/placebo DRUG

Subjects randomized to be treated with Regorafenib/placebo will receive once a day 160 mg po (four tablets of 40 mg) for 3 weeks of every 4 weeks cycle (3 weeks on and 1 week off) Duration of one cycle is 28 days

Regorafenib/placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• histologically proven intra-hepatic or hilum cholangiocarcinoma (mass forming, not "liniting" tumor), locally advanced unresectable or metastatic
• progression documented after GEM-CDDP (or GEM-OX), or gemcitabine alone followed or preceded by platinum-based (CDDP or oxaliplatin) chemotherapy
• age \> 18 years
• ECOG PS 0/1 at study entry
• measurable disease according to RECIST version 1.1
• Adequate bone marrow, liver and renal function as assessed by the following laboratory requirementsconducted within 7 days of starting to study treatment:
• oSerum creatinine \<1.5x upper reference range
• oTotal bilirubin \<1.5x ULN
• oAlanine transaminase (ALT) and aspartate aminotransferase (AST) \< 2.5x ULN (\<5x ULN forpatients with liver involvement of their cancer).
• oAmylase and lipase \<1.5x ULN.
• life expectancy of at least 12 weeks
• effective contraception for both male and female patients if the risk of conception exists
• negative proteinuria on dipstick or 24 hours proteinuria\<1000mg
• signed written informed consent

You may not qualify if:

• unability to take oral medication
• any malabsorption condition
• patients taking strong cytochrome P (CYP) CYP3A4 inhibitors (eg. Clarithromycin, indinavir,itraconazole, ketoconazole, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telithromycin,voriconazole) or strong CYP3A4 inducers (eg. Carbamazepine, phenobarbital, phenytoin, rifampin, St-John's Wort) (see section 8)
• persistent proteinuria \>3.5g/24 hours measured by urine protein-creatinine ratio from a random urinesample (persistent proteinuria \>3 non-healing woud, ulcer, or bone fracture
• any hemorrhage or bleeding event ≥ CTCAE Grade 3 within 4 weeks prior to the start of studymedication
• interstitial lund disease with ongoing signs and symptoms at the time of informed consent
• uncontrolled concurrent CNS, cardiac, infectious diseases, hypertension
• history of myocardial infarction, deep venous or arterial thrombosis, cerebrovascular accident (CVA) during the last 6 months
• previous exposure to anti-VEGF targeting therapy (including Regorafenib) and to signal transduction inhibitors
• known hypersensitivity to any of the components of study treatments
• previous malignancy in the last past 5 years except basal cell cancer of the skin or preinvasive cancer of the cervix
• pregnant or lactating women, or patients of both genders with procreative potential not using adequate contraceptive methods
• medical or psychological conditions that would not permit the patient to complete the study or sign inform consent
• unstable angina, congestive heart failure ≥NYHA class II
• uncontrolled hypertension despite optimal management (systolic blood pressure \>150 mmHg or diastolic pressure \> 90mmHg)

Sponsors & Collaborators

• Erasme University Hospital: lead

Study Sites (12)

CH Jolimont

Haine-Saint-Paul, Hainaut, 7100, Belgium

Location

University Hospitals of Antwerp

Antwerp, 2650, Belgium

Location

AZ St-Lucas Brugge

Bruges, 8310, Belgium

Location

Erasme University Hospital

Brussels, 1070, Belgium

Location

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

Location

Grand Hôpital de Charleroi

Charleroi, 6000, Belgium

Location

AZ St-Lucas Gent

Ghent, 9000, Belgium

Location

UZ Gent

Ghent, 9000, Belgium

Location

AZ Groeninge

Kortrijk, 8500, Belgium

Location

CHC St-Joseph

Liège, 4000, Belgium

Location

Hôpital Ambroise Paré

Mons, 7000, Belgium

Location

CMSE

Namur, 5000, Belgium

Location

Related Publications (1)

• Demols A, Borbath I, Van den Eynde M, Houbiers G, Peeters M, Marechal R, Delaunoit T, Goemine JC, Laurent S, Holbrechts S, Paesmans M, Van Laethem JL. Regorafenib after failure of gemcitabine and platinum-based chemotherapy for locally advanced/metastatic biliary tumors: REACHIN, a randomized, double-blind, phase II trial. Ann Oncol. 2020 Sep;31(9):1169-1177. doi: 10.1016/j.annonc.2020.05.018. Epub 2020 May 25.

  PMID: 32464280 DERIVED

MeSH Terms

Conditions

Cholangiocarcinoma; Neoplasm Metastasis

Interventions

regorafenib; Exercise

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Anne Demols, MD, PhD

  Erasme University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 26, 2014
• First Posted: June 13, 2014
• Study Start: March 14, 2014
• Primary Completion: March 1, 2019
• Study Completion: December 1, 2020
• Last Updated: July 31, 2020

Record last verified: 2020-07

Locations

BE (12)