STREAM: Regorafenib Monotherapy as Second-line Treatment of Patients With RAS-mutant Advanced Colorectal Cancer
Study Details
Study Description
Brief Summary
The purpose of this study is to purpose of this study is to assess if regorafenib is active enough, in terms of 6-month progression-free rate, to warrant further comparative studies in patients with RAS-mutant advanced colorectal cancer who have progressed after first-line oxaliplatin-based chemotherapy plus bevacizumab.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: regorafenib
|
Drug: regorafenib
Patients will receive regorafenib orally 160 mg once daily for the first 3 weeks of each 4-week cycle.
|
Outcome Measures
Primary Outcome Measures
- the rate of evaluable patients alive and not progressed at 6 months [6 months]
Secondary Outcome Measures
- worst grade toxicity per patient [every 4 weeks up to 1 year]
evaluated according to RECIST 1.1
- number of patients with complete plus partial response [6 months]
- progression free survival [up to one year]
the time from registration to progression or death without progression
- overall survival [up to 2 years]
as the time from registration to the date of death due to any cause
Eligibility Criteria
Criteria
Inclusion Criteria:
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Histologically confirmed diagnosis of colorectal adenocarcinoma
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Any RAS mutation that prevent treatment with anti-EGFR antibodies
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Stage IV
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Measurable disease according to RECIST v. 1.1
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Disease progression during or following a treatment with fluoropyrimidine, oxaliplatin and bevacizumab, and a treatment with irinotecan is not considered immediately mandatory by the Investigator
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Age ≥ 18 years
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ECOG Performance Status 0-1
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Neutrophils > 1500 / mm3, platelets > 100,000 / mm3, and hemoglobin > 9 g/dL without transfusion or granulocyte-colony stimulating factor (G-CSF) and other hematopoietic growth factors.
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Bilirubin level < 1.5 x ULN
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Glomerular filtration rate > 30 mL/min/1.73 m2 according to the Modified Diet in Renal Disease abbreviated formula
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AST (SGOT) and ALT (SGPT) ≤ 3.0 x ULN (≤ 5 x ULN if liver metastasis are present)
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Alkaline phosphatase ≤ 2.5 x ULN (≤ 5 x ULN if liver metastasis are present)
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Serum creatinine < 1.5 x ULN
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Amylase and lipase ≤ 1.5 x ULN
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INR and aPTT ≤ 1.5 x ULN. Subjects who are therapeutically treated with an agent such as warfarin or heparin will be allowed to participate if no underlying abnormality in coagulation parameters exists per medical history.
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Understand, be willing to give consent, and sign the written informed consent form (ICF) prior to undergoing any study-specific procedure.
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If female and of childbearing potential, have a negative result on a pregnancy test performed a maximum of 7 days before initiation of study treatment.
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If potentially childbearing female, or if male, agree to use adequate contraception (eg, abstinence, intrauterine device, oral contraceptive, or double-barrier method) from the date on which the ICF is signed until 8 weeks after the last dose of study drug.
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Life expectancy of greater than 3 months
Exclusion Criteria:
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Previous treatment with regorafenib or irinotecan
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Are 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)
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Have had a major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to initiation of study treatment
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Have congestive heart failure classified as New York Heart Association Class 2 or higher
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Have had unstable angina (angina symptoms at rest) or new-onset angina < 3 months prior to screening.
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Have had a myocardial infarction < 6 months prior to initiation of study treatment.
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Have cardiac arrhythmias requiring anti-arrhythmic therapy, with the exception of beta blockers or digoxin.
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Have had arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism within 6 months prior to the initiation of study treatment
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Symptomatic brain metastases or meningeal tumors
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Patients with evidence or history of bleeding diathesis
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Uncontrolled hypertension (systolic blood pressure [SBP] >140 mmHg or diastolic blood pressure [DBP] > 90 mmHg)
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Have interstitial lung disease with ongoing signs and symptoms at the time informed consent is obtained
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Have persistent proteinuria > 3.5 g/24 hours measured by urine protein creatinine ratio from a random urine sample (< Grade 3, CTCAE v 4.0).
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Have unresolved toxicity higher than National Cancer Institute-Common Terminology for Adverse Events version 4.0 (CTCAE v 4.0) Grade 1 attributed to any prior therapy/procedure, excluding alopecia and/or oxaliplatin-induced neurotoxicity ≤ Grade 2 and hemoglobin ≥ 9 g/dL as per inclusion criteria
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Patients who cannot take oral medication, who require intravenous alimentation, have had prior surgical procedures affecting absorption, or have active peptic ulcer disease
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Pregnant or lactating women
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Any other malignancies within 5 years (except for adequately treated carcinoma in situ of the cervix or non melanoma skin cancer)
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Any unstable systemic disease (including active infections, any significant hepatic, renal or metabolic disease), metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of regorafenib or render the patient at high risk for treatment complications
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Sexually active males and females (of childbearing potential) unwilling to practice contraception during the study.
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Have any other serious or unstable illness, or medical, psychological, or social condition, that could jeopardize the safety of the subject and/or his/her compliance with study procedures, or may interfere with the subject's participation in the study or evaluation of the study results.
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Have a known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation of the study drugs.
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Have a close affiliation with the investigational site (eg, be a close relative of the investigator) or be a dependent person (eg, be an employee or student working at the investigational site).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | AO G. Rummo | Benevento | Italy | ||
| 2 | Istituto Nazionale Tumori Fondazione G. Pascale | Napoli | Italy | ||
| 3 | Seconda Università di Napoli | Napoli | Italy | ||
| 4 | AO S. Carlo | Potenza | Italy |
Sponsors and Collaborators
- National Cancer Institute, Naples
Investigators
- Principal Investigator: Antonio Avallone, M.D., National Cancer Institute, Naples
- Principal Investigator: Alfredo Budillon, M.D., National Cancer Institute, Naples
- Principal Investigator: Francesco Perrone, M.D., National Cancer Institute, Naples
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- STREAM
- 2015-001105-13