A Study of Ruxolitinib in Combination With Regorafenib in Subjects Metastatic Colorectal Cancer

• Register: EUCTR
• Last refreshed on: 3 April 2017
• Main ID: EUCTR2013-004714-18-GB
• Date of registration: 03/10/2014
• Prospective Registration: Yes
• Primary sponsor: Incyte Corporation
• Public title: A Study of Ruxolitinib in Combination With Regorafenib in Subjects Metastatic Colorectal Cancer
• Scientific title: A Randomized, Double-Blind Study of Ruxolitinib or Placebo in Combination With Regorafenib in Subjects With Relapsed or Refractory Metastatic Colorectal Cancer - Ruxolitinib in Combination With Regorafenib in Metastatic Colorectal Cancer
• Date of first enrolment: 05/01/2015
• Target sample size: 420
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-004714-18
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Israel, Italy, Korea, Republic of, Spain, United Kingdom

Contacts

• Name: Clinical Trials Information
• Affiliation: Incyte

• Name: Clinical Trials Information
• Affiliation: Incyte

Key inclusion & exclusion criteria

Inclusion criteria:
• Male or female 18 years or older.
• Histologically or cytologically confirmed adenocarcinoma of the colon or rectum that is metastatic.
• Previous treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy; an anti-VEGF therapy (if no contraindication); and if KRAS wild type and no contraindication, an anti-EGFR therapy; and progressed following the last administration of approved therapy.
• Radiographically measurable or evaluable disease (per RECIST 1.1).
• Eastern Cooperative Oncology Group performance status of 0 to 2.
• Three or more weeks have elapsed from the completion of previous treatment regimen and subjects must have recovered or be at a new stable baseline from any related toxicities.
• Radiotherapy to disease sites is allowed provided:
- Four or more weeks have elapsed since the completion of radiation therapy.
- Subjects who received palliative radiation treatment to a limited field or on an accelerated schedule within the last 7 days are eligible
- Disease sites within the field of prior irradiation have subsequently progressed or there are other metastatic disease sites outside the field of prior irradiation.
- All treatment related toxicities have resolved or are at a new stable baseline.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 210
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 210

Exclusion criteria:
Subjects who meet any of the following will not be included in the study:
• Received prior treatment with regorafenib.
• Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption of drugs.
• History of abdominal fistula or gastrointestinal perforation at any point within 6 months prior to day 1 of study drug administration, unless surgically repaired.
• Active peptic ulcer disease, inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), diverticulitis, or other gastrointestinal conditions with increased risk of perforation or gastrointestinal bleeding.
• Recent history (=4 weeks of Day 1 of study drug administration) of a major surgery or significant traumatic injury.
• Recent history (= 3 months) or ongoing partial or complete bowel obstruction unless corrected with surgery.
• Blood pressure = 140/90 mmHg
• Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment.
• Known central nervous system metastases or history of uncontrolled seizures.
• Clinically significant cardiac disease including unstable angina, acute myocardial infarction within 6 months from Day 1 of study drug administration, New York Heart Association Class II, III, or IV congestive heart failure, and arrhythmia requiring therapy.
• Creatinine clearance < 50 mL/min measured or calculated by Cockroft-Gault equation
• Inadequate hepatic, and bone marrow function as evidenced by:
- Absolute neutrophil count < 1.5 × 109/L.
- Platelets < 100 × 109/L.
- Hemoglobin < 9 g/dL (transfusions are permitted to achieve baseline hemoglobin level).
- ALT/AST > 2.5 × the upper limit of normal (ULN); or > 5 × ULN in the presence of liver metastases.
- Total bilirubin > 1.5 × ULN (if total bilirubin is > 1.5 × ULN then the subject may participate if the direct bilirubin is = 1.5 × ULN).
• Concurrent anticancer therapy
• Subjects who participated in any other study in which an investigational study drug was received within 28 days prior to first dose.
• Current or previous other malignancy within 5 years of study entry, except cured basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive malignancy.
• Known HIV infection.
• HBV or HCV viremia or at risk for HBV or HCV reactivation.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Relapsed or refractory metastatic colorectal cancer
MedDRA version: 17.0 Level: PT Classification code 10052358 Term: Colorectal cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 17.0 Level: PT Classification code 10010030 Term: Colorectal cancer recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 17.0 Level: LLT Classification code 10052362 Term: Metastatic colorectal cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 17.0 Level: PT Classification code 10061451 Term: Colorectal cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Trade Name: Jakafi
Product Name: ruxolitinib
Product Code: INCB018424
Pharmaceutical Form: Tablet
INN or Proposed INN: ruxolitinib
Current Sponsor code: INCB018424
Other descriptive name: RUXOLITINIB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Trade Name: Stivarga
Product Name: regorafenib
Pharmaceutical Form: Tablet
INN or Proposed INN: regorafenib
CAS Number: 755037-03-7
Other descriptive name: REGORAFENIB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-

Primary Outcome(s)

Main Objective: Part 1 (Safety Run-in)
• To determine the doses of ruxolitinib and regorafenib that are safe and tolerable when administered in combination.
Part 2 (Randomized Phase)
• To evaluate and compare the OS of subjects with metastatic CRC when treated with ruxolitinib in combination with regorafenib versus regorafenib alone.

Primary end point(s): The primary endpoint OS is defined as the interval from date of randomization to death due to any cause.

Timepoint(s) of evaluation of this end point: The primary endpoint OS is defined as the interval from date of randomization to death due to any cause. Subjects without death observed at the time of the analysis will be censored at last date known to be alive.

Secondary Objective: • To evaluate and compare the efficacy of the 2 treatment groups with respect to PFS.
• To evaluate and compare the efficacy of the 2 treatment groups with respect to overall tumor response and duration of response.
• To evaluate and compare disease control of ruxolitinib in combination with regorafenib versus regorafenib alone.
• To evaluate and compare the safety and tolerability of ruxolitinib in combination with regorafenib versus regorafenib alone.

Secondary Outcome(s)

Secondary end point(s): PFS, defined as the interval from date of randomization to the earlier of death or disease progression by RECIST 1.1 as assessed by the investigator.

ORR by treatment groups along with 95% exact CIs.

Timepoint(s) of evaluation of this end point: The interval from date of randomization to the earlier of death or disease progression by RECIST 1.1 as assessed by the investigator

Secondary ID(s)

2013-004714-18-IT

INCB18424-267

Source(s) of Monetary Support

Incyte Corporation