Regorafenib+FOLFIRI Versus Placebo+FOLFIRI as 2nd Line Tx in Metastatic Colorectal Cancer

Completed · Phase 2 · Has a placebo group

Conditions studied: Colorectal Cancer Metastatic

In brief

This randomized (2:1), multi-center, placebo-controlled, phase II efficacy study is designed to compare PFS between regorafenib + FOLFIRI chemotherapy (ARM A) versus placebo + FOLFIRI (ARM B) in patients with mCRC previously treated with a FOLFOX regimen.

Key facts

Study ID

NCT01298570

Run by

UNC Lineberger Comprehensive Cancer Center

People needed

181

Starts

2011-04-07

Expected to finish

2020-10-02

Last updated by the study team

2021-01-06

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Subject must meet all of the inclusion criteria to participate in this study:
• Age ≥18 years of age (no upper age limit)
• Histological or cytological documentation of adenocarcinoma of the colon or rectum
• Archived, paraffin-embedded tissue block (primary or metastatic) available for genomic studies required
• Metastatic disease not amenable to surgical resection with curative intent
• Progression during or within 6 months following administration of a standard regimen[2] for treatment of metastatic disease that included oxaliplatin with any of the following agents with or without bevacizumab:
• 5-fluorouracil (F-FU) with or without leucovorin or levoleucovorin
• Capecitabine
• Note: In patients receiving FOLFOX, oxaliplatin is sometimes discontinued due to toxicity or as part of maintenance therapy strategy. If such patients progress while on 5-FU alone, they are eligible for this trial. As an example, a patient who is begun on FOLFOX or CapeOx (capecitabine with oxaliplatin, with or without bevacizumab), whose oxaliplatin is held for neurotoxicity and who is switched to capecitabine monotherapy or capecitabine with bevacizumab, would be considered to have had one prior therapy.
• OR
• Patients who develop metastatic disease within 9 months of adjuvant FOLFOX for stage II or III colon cancer
• Measurable disease, defined as at least 1 unidimensionally measurable lesion on a CT scan as defined by RECIST 1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤1 (see Appendix C)
• Life expectancy of at least 3 months
• Adequate bone marrow, renal, and hepatic function, as evidenced by the following:
• absolute neutrophil count (ANC) ≥1,500/mm3
• platelets ≥100,000/mm3
• hemoglobin ≥9.0 g/dL
• serum creatinine ≤1.5 x upper limit of normal (ULN)
• Glomerular filtration rate (GFR) ≥30 ml/min/1.73m2 (see Appendix A)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3x ULN ( ≤5.0 × ULN for patients with liver involvement of their cancer
• Bilirubin ≤1.5 X ULN
• Alkaline phosphatase ≤3 x ULN (≤5 x ULN with liver involvement of their cancer)
• Amylase and lipase ≤1.5 x ULN
• Spot urine must not show 1+ or more protein in urine or the patient will require a repeat urine analysis.If repeat urinalysis shows 1+ protein or more, a 24-hour urine collection will be required and must show total protein excretion <1000 mg/24 hours

You may not qualify if…

• Any subject meeting any of the following exclusion criteria at baseline will be ineligible for study participation:
• Prior treatment with regorafenib
• More than 1 prior chemotherapy regimen for mCRC (see section 3.1.5) Previous adjuvant FOLFOX based chemotherapy is allowed. Prior FOLFIRI or single agent irinotecan is prohibited.
• Known history of or concomitant malignancy likely to affect life expectancy in the judgment of the investigator
• Pregnant or breastfeeding patients. Women of childbearing potential must have a pregnancy test performed a maximum of 7 days before start of FOLFIRI treatment, and a negative result must be documented before start of treatment.
• History of Gilbert's syndrome
• Known Dihydropyrimidine dehydrogenase (DPD) deficiency
• Pernicious anemia or other anemias due to vitamin B12 deficiency (due to potential masking of deficiency with leucovorin)
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of Day 1 of treatment with FOLFIRI
• Radiotherapy within 4 weeks prior to first dose of FOLFIRI
• Active cardiac disease including any of the following:
• Congestive heart failure (New York Heart Association (NYHA)) ≥Class 2 (see Appendix D)
• Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months). Myocardial infarction less than 6 months before start of Day 1 of FOLFIRI
• Cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted)
• Uncontrolled hypertension. (Systolic blood pressure >150 mmHg or diastolic pressure >90 mmHg despite optimal medical management)
• Patients with pheochromocytoma
• Arterial thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), or pulmonary embolism within the 6 months before start of FOLFIRI
• Ongoing infection >Grade 2 according to NCI Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v. 4.0)
• Known history of human immunodeficiency virus (HIV) infection
• Known history of chronic hepatitis B or C
• Patients with seizure disorder requiring medication
• Symptomatic metastatic brain or meningeal tumors unless the patient is >6 months from definitive therapy, has a negative imaging study within 4 weeks of FOLFIRI initiation, and is clinically stable with respect to the tumor at the time of study entry. Also, the patient must not be undergoing acute steroid therapy or taper (chronic steroid therapy is acceptable provided that the dose is stable for one month prior to and following screening radiographic studies)
• History of organ allograft
• Evidence or history of bleeding diathesis. Any hemorrhage or bleeding event > Grade 4 within 4 weeks of start of FOLFIRI
• Non-healing wound, ulcer, or bone fracture

Where it is running

• Rocky Mountain Cancer Centers — Denver, Colorado, United States
• Mount Sinai Medical Center-Miami — Miami, Florida, United States
• Moffitt Cancer Center — Tampa, Florida, United States
• Emory University — Atlanta, Georgia, United States
• Georgia Cancer Specialists — Atlanta, Georgia, United States
• Indiana University Simon Cancer Center — Indianapolis, Indiana, United States
• University of Louisville James Brown Cancer Center — Louisville, Kentucky, United States
• North Shore Long Island Jewish Health System — Manhasset, New York, United States
• New York University Langone Medical Center — New York, New York, United States
• Seby B. Jones Cancer Center — Boone, North Carolina, United States
• University of North Carolina — Chapel Hill, North Carolina, United States
• Carolinas HealthCare System — Charlotte, North Carolina, United States
• Southeast Medical Oncology Center — Goldsboro, North Carolina, United States
• The Moses Cone Regional Cancer Center — Greensboro, North Carolina, United States
• Leo W. Jenkins Cancer Center at ECU Medical School — Greenville, North Carolina, United States
• First Health of the Carolinas, Moore Regional Hospital — Pinehurst, North Carolina, United States
• Rex Cancer Center at Rex Hospital — Raleigh, North Carolina, United States
• Wake Forest University Comprehensive Cancer Center — Winston-Salem, North Carolina, United States
• University of Cincinnati — Cincinnati, Ohio, United States
• Ohio State University Comprehensive Cancer Center — Columbus, Ohio, United States
• University of Virginia — Charlottesville, Virginia, United States
• Portsmouth Naval Medical Center — Portsmouth, Virginia, United States
• Multicare Regional Cancer Center — Tacoma, Washington, United States
• Ireland Cooperative Clinical Research Group — Dublin, Ireland

Full record on ClinicalTrials.gov

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