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Regorafenib Versus Placebo to Treat Cholangiocarcinoma (REACHIN)

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ClinicalTrials.gov Identifier: NCT02162914
Recruitment Status : Active, not recruiting
First Posted : June 13, 2014
Last Update Posted : March 20, 2019
Sponsor:
Information provided by (Responsible Party):
Erasme University Hospital

Tracking Information
First Submitted Date  ICMJE May 26, 2014
First Posted Date  ICMJE June 13, 2014
Last Update Posted Date March 20, 2019
Actual Study Start Date  ICMJE March 14, 2014
Actual Primary Completion Date March 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 10, 2014)
Improve median PFS [ Time Frame: 6 to 12 weeks ]
The primary endpoint is to improve median PFS from 6 weeks to 12 weeks in Regorafenib group.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02162914 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 13, 2014)
  • Evaluation of response rate [ Time Frame: At pretreatment visit (14 to 1 days before treatment initiation), every 6 weeks for 3 times then every 8 weeks until progression ]
    -Evaluation of tumor response will be done based on radiological RECIST criteria version 1.1 evaluation (thoraco-abdominal CT scan);
  • Correlation between radiological response and metabolic response [ Time Frame: At pretreatment visit (14 to 1 days before treatment initiation) ]
    Correlation between radiological response (using RECIST criteria version 1.1) and metabolic response using PET imaging (SUV max modifications). This will only be done if SUV max of the tumor inside the liver at pre-treatment visit is ≥ 175% of the SUV max of the normal liver.
  • Correlation between radiologic response rate and "Dynamic tumor response rate" [ Time Frame: At day 1 (pre-treatment) and day 15 of cycle 1 ]
    Correlation between radiologic response rate (RECIST criteria version 1.1) and "Dynamic tumor response rate". Dynamic response rate is defined by a 20% modification of tumoral perfusion status determined by quantitative DCE-MRI after 14 days of treatment (D1 compared to D15 values);
  • Correlation between dynamic tumor response rate and metabolic response rate [ Time Frame: At cycle 1 day 15 ]
    Correlation between dynamic tumor response rate and metabolic response rate (Pet CT) when first Pet CT is positive
  • Evaluation of Overall Survival (OS) [ Time Frame: After 1 year (March 2015) ]
    Evaluation of OS at one year.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 10, 2014)
  • Evaluation of response rate [ Time Frame: At pretreatment visit, every 6 weeks for 3 times then every 8 weeks until progression ]
    -Evaluation of tumor response will be done based on radiological RECIST criteria version 1.1 evaluation (thoraco-abdominal CT scan);
  • Correlation between radiological response and metabolic response [ Time Frame: At pretreatment visit ]
    Correlation between radiological response (using RECIST criteria version 1.1) and metabolic response using PET imaging (SUV max modifications). This will only be done if SUV max of the tumor inside the liver at pre-treatment visit is ≥ 175% of the SUV max of the normal liver.
  • Correlation between radiologic response rate and "Dynamic tumor response rate" [ Time Frame: At day 1 (pre-treatment) and day 15 of cycle 1 ]
    Correlation between radiologic response rate (RECIST criteria version 1.1) and "Dynamic tumor response rate". Dynamic response rate is defined by a 20% modification of tumoral perfusion status determined by quantitative DCE-MRI after 14 days of treatment (D1 compared to D15 values);
  • Correlation between dynamic tumor response rate and metabolic response rate [ Time Frame: At cycle 1 day 15 ]
    Correlation between dynamic tumor response rate and metabolic response rate (Pet CT) when first Pet CT is positive
  • Evaluation of Overall Survival (OS) [ Time Frame: After 1 year (March 2015) ]
    Evaluation of OS at one year.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Regorafenib Versus Placebo to Treat Cholangiocarcinoma
Official Title  ICMJE REGORAFENIB AFTER FAILURE OF GEMCITABINE AND PLATINUM-BASED CHEMOTHERAPY FOR LOCALLY ADVANCED (NON RESECTABLE) AND METASTATIC INTRA-HEPATIC OR HILAR CHOLANGIOCARCINOMA: A Randomized Double-blinded Phase II Trial.
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).

Detailed Description 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).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Cholangiocarcinoma
Intervention  ICMJE
  • Drug: Regorafenib/active
    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
  • Drug: Regorafenib/placebo
    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
Study Arms  ICMJE
  • Active Comparator: Regorafenib/active
    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.
    Intervention: Drug: Regorafenib/active
  • Placebo Comparator: Regorafenib/placebo
    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.
    Intervention: Drug: Regorafenib/placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: June 10, 2014)
66
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2020
Actual Primary Completion Date March 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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)
  • pheochromocytoma
  • HIV infection
  • active chronic hepatitis B or C with a need for antiviral treatment
  • liver failure, cirrhosis Chil Pugh B or C
  • brain metastasis
  • major surgery, open biopsy or significant traumatic injury within 4 weeks prior to the first dose of treatment
  • intra-hepatic locoregional therapy (DC Beads, SIRT)
  • history of organ allograft
  • ongoing infection
  • renal failure requiring dialysis
  • patients receiving or having received any investigational treatment within 4 weeks prior to study entry, or participating to another clinical study
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02162914
Other Study ID Numbers  ICMJE 2012-005626-30
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Erasme University Hospital
Study Sponsor  ICMJE Erasme University Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Anne Demols, MD, PhD Erasme University Hospital
PRS Account Erasme University Hospital
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP