Regorafenib in Treating Patients with Newly Diagnosed Metastatic Colorectal Cancer
This pilot phase II trial studies how well regorafenib works in treating patients with newly diagnosed colorectal cancer that has spread to other places in the body. Regorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Inclusion Criteria
- Life expectancy of at least 12 weeks (3 months)
- Untreated for metastatic colorectal cancer or progression on any first line fluorouracil (5-FU) containing regimen (such as leucovorin calcium, fluorouracil, oxaliplatin [FOLFOX] or irinotecan, fluorouracil, leucovorin calcium [FOLFIRI])
- Histologically proven colorectal adenocarcinoma
- Metastatic disease, unresectable disease involving one or more sites including liver, lung, lymph nodes and peritoneum, with each nodule measuring =< 3 cm OR no more than two sites of disease (two nodules) > 4.5 cm
- Eastern Cooperative Oncology Group (ECOG) 0 or 1
- Total bilirubin =< 1.5 x the upper limits of normal (ULN)
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN (=< 5 x ULN for subjects with liver involvement of their cancer)
- Alkaline phosphatase limit =< 2.5 x ULN (=< 5 x ULN for subjects with liver involvement of their cancer)
- Lipase =< 1.5 x the ULN
- Creatinine =< 1.5 x the ULN
- Platelet count >= 100,000/mm^3; blood transfusion to meet the inclusion criteria will not be allowed
- Hemoglobin (Hb) >= 9 g/dL; blood transfusion to meet the inclusion criteria will not be allowed
- Absolute neutrophil count (ANC) >= 1500/mm^3; blood transfusion to meet the inclusion criteria will not be allowed
- Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of study drug; post-menopausal women (defined as no menses for at least 1 year) and surgically sterilized women are not required to undergo a pregnancy test
- Subjects (men and women) of childbearing potential must agree to use adequate contraception beginning at the signing of the informed consent form (ICF) until at least 3 months after the last dose of study drug; the definition of adequate contraception will be based on the judgment of the principal investigator or a designated associate
- Subject must be able to swallow and retain oral medication
- If the patient is enrolled at Memorial Sloan-Kettering (MSK) he/she must consent to a pre and post treatment biopsy (or have archived tissue available for the pretreatment analysis); pretreatment archival tissue for patients enrolled outside of MSK should be submitted to MSK; if there is no archival tissue available, a repeat biopsy is not required for non-MSK patients
Exclusion Criteria
- Uncontrolled hypertension (systolic pressure > 140 mm Hg or diastolic pressure > 90 mm Hg [National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (v4.0)] on repeated measurement) despite optimal medical management
- Active or clinically significant cardiac disease including: * Congestive heart failure - New York Heart Association (NYHA) > class II * Active coronary artery disease * Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin * Unstable angina (anginal symptoms at rest), new-onset angina within 3 months before randomization, or myocardial infarction within 6 months before randomization
- Evidence or history of bleeding diathesis or coagulopathy
- Any hemorrhage or bleeding event >= NCI CTCAE grade 3 within 4 weeks prior to start of study medication
- Subjects with any previously untreated or concurrent cancer that is distinct in primary site or
- Recent history of prior cancer except cervical cancer in-situ, treated basal cell carcinoma, or superficial bladder tumor; subjects surviving a cancer that was curatively treated and without evidence of disease for more than 3 years before enrollment are allowed
- Known history of human immunodeficiency virus (HIV) infection or current chronic or active hepatitis B or C infection requiring treatment with antiviral therapy
- Ongoing infection > grade 2 NCI-CTCAE v 4.0
- Symptomatic metastatic brain or meningeal tumors
- Presence of a non-healing wound, non-healing ulcer, or bone fracture
- Patients with seizure disorder requiring medication
- Interstitial lung disease with ongoing signs and symptoms at the time of informed consent
- Pleural effusion or ascites that causes respiratory compromise (>= NCI-CTCAE version 4.0 grade 2 dyspnea)
- History of organ allograft (including corneal transplant)
- Any malabsorption condition
- Women who are pregnant or breast-feeding
- Any condition which, in the investigator’s opinion, makes the subject unsuitable for trial participation
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of study medication
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT02023333.
PRIMARY OBJECTIVES:
I. To determine the 16 week progression free survival, in patients with previously untreated, asymptomatic or minimally symptomatic metastatic colorectal cancer.
SECONDARY OBJECTIVES:
I. Overall survival.
II. Disease control rate.
III. Duration of stable disease.
IV. Toxicity.
TERTIARY OBJECTIVES:
I. To evaluate pretreatment tumor samples to attempt to identify molecular markers of responsiveness or resistance to regorafenib.
II. To obtain and evaluate tumor tissue at the time of progression to evaluate genetic alterations in subclones and for markers of resistance to regorafenib.
III. To obtain and evaluate circulating deoxyribonucleic acid (DNA) pre and throughout treatment to assess for genetic alterations prior to clinical or radiographic progression.
OUTLINE:
Patients receive regorafenib orally (PO) once daily (QD) for 3 weeks. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 14 days, periodically for 1 year, and then annually thereafter.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationMemorial Sloan Kettering Cancer Center
Principal InvestigatorAndrea Cercek
- Primary ID13-211
- Secondary IDsNCI-2014-00002
- ClinicalTrials.gov IDNCT02023333