Regorafenib Monotherapy as Second-line Treatment of Patients With RAS-mutant Advanced Colorectal Cancer

NCT02619435 | Unknown Phase 2

• 2 other identifiers: STREAM2015-001105-13
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 4

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.

Conditions

Advanced Colorectal Cancer

Keywords

RAS-mutant

Outcome Measures

Primary Outcomes (1)

• the rate of evaluable patients alive and not progressed at 6 months

  6 months

Secondary Outcomes (4)

• worst grade toxicity per patient

  every 4 weeks up to 1 year

• number of patients with complete plus partial response

  6 months

• progression free survival

  up to one year

• overall survival

  up to 2 years

Study Arms (1)

regorafenib

EXPERIMENTAL

Drug: regorafenib

Interventions

regorafenib DRUG

Patients will receive regorafenib orally 160 mg once daily for the first 3 weeks of each 4-week cycle.

regorafenib

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed diagnosis of colorectal adenocarcinoma
• Any RAS mutation that prevent treatment with anti-EGFR antibodies
• Stage IV
• Measurable disease according to RECIST v. 1.1
• 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
• Age ≥ 18 years
• ECOG Performance Status 0-1
• 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.
• Bilirubin level \< 1.5 x ULN
• Glomerular filtration rate \> 30 mL/min/1.73 m2 according to the Modified Diet in Renal Disease abbreviated formula
• AST (SGOT) and ALT (SGPT) ≤ 3.0 x ULN (≤ 5 x ULN if liver metastasis are present)
• Alkaline phosphatase ≤ 2.5 x ULN (≤ 5 x ULN if liver metastasis are present)
• Serum creatinine \< 1.5 x ULN
• Amylase and lipase ≤ 1.5 x ULN
• 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.

You may not qualify if:

• Previous treatment with regorafenib or irinotecan
• 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)
• Have had a major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to initiation of study treatment
• Have congestive heart failure classified as New York Heart Association Class 2 or higher
• Have had unstable angina (angina symptoms at rest) or new-onset angina \< 3 months prior to screening.
• Have had a myocardial infarction \< 6 months prior to initiation of study treatment.
• Have cardiac arrhythmias requiring anti-arrhythmic therapy, with the exception of beta blockers or digoxin.
• 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
• Symptomatic brain metastases or meningeal tumors
• Patients with evidence or history of bleeding diathesis
• Uncontrolled hypertension (systolic blood pressure \[SBP\] \>140 mmHg or diastolic blood pressure \[DBP\] \> 90 mmHg)
• Have interstitial lung disease with ongoing signs and symptoms at the time informed consent is obtained
• 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).
• Patients who cannot take oral medication, who require intravenous alimentation, have had prior surgical procedures affecting absorption, or have active peptic ulcer disease
• Pregnant or lactating women

Sponsors & Collaborators

• National Cancer Institute, Naples: lead

Study Sites (4)

AO G. Rummo

Benevento, Italy

Location

Istituto Nazionale Tumori Fondazione G. Pascale

Napoli, Italy

Location

Seconda Università di Napoli

Napoli, Italy

Location

AO S. Carlo

Potenza, Italy

Location

MeSH Terms

Interventions

regorafenib

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2015
• First Posted: December 2, 2015
• Study Start: November 1, 2015
• Primary Completion: November 1, 2024
• Study Completion: November 1, 2024
• Last Updated: March 24, 2023

Record last verified: 2023-03

Locations

IT (4)