Regorafenib in Good Performance Status Patients With Newly Diagnosed Metastatic Colorectal Adenocarcinoma

Metastatic Colorectal Adenocarcinoma Clinical Trial

Official title:

Phase II Study of Regorafenib in Good Performance Status Patients With Newly Diagnosed Metastatic Colorectal Adenocarcinoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02023333
• Other study ID #: 13-211
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: December 2013
• Est. completion date: December 2024

Study information

• Verified date: January 2024
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the good and bad effects when regorafenib is used instead of standard combination chemotherapy. It is not known if taking regorafenib versus standard chemotherapy will have better, worse or the same results.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 11
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age = 18 years.
• Life expectancy of at least 12 weeks (3 months).
• Untreated for metastatic colorectal cancer, or progression on any first line 5-FU containing regimen (such as FOLFOX or 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 =3cm OR no more than two sites of disease (two nodules) >4.5 cm.
• ECOG 0 or 1
• Adequate bone marrow, liver and liver function as assessed by the following laboratory

requirements:

• Total bilirubin = 1.5 x the upper limits of normal (ULN)
• Alanine aminotransferase (ALT) and aspartate amino-transferase (AST) = 2.5 xULN (= 5 x ULN for subjects with liver involvement of their cancer)
• Alkaline phosphastase 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 = 100000 /mm3
• hemoglobin (Hb) = 9 g/dL,
• absolute neutrophil count (ANC) = 1500/mm3.
• 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 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 site principal investigator or a designated associate.
• Subject must be able to swallow and retain oral medication.
• If the patient is enrolled at 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 [NCI-CTCAE 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 v4.0.
• 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.

Related Conditions & MeSH terms

• Adenocarcinoma
• Metastatic Colorectal Adenocarcinoma

Intervention

Drug:
• Regorafenib
All patients that meet the eligibility criteria who have signed informed consent and have enrolled on the trial will be treated with regorafenib, daily 3 weeks on 1 week off for all cycles. Dose will be escalated to 120 mg in week 2 of cycle 1 and all remaining cycles if no excess toxicity is experienced by the patient at the discretion of the treating physician.

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering Cancer Center at Basking Ridge	Basking Ridge	New Jersey
United States	Downstate Medical Center	Brooklyn	New York
United States	Memorial Sloan Kettering Cancer Center at Commack	Commack	New York
United States	Queens Cancer Center of Queens Hospital	Jamaica	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Memorial Sloan Kettering Cancer Center at Mercy Medical Center	Rockville Centre	New York
United States	Memorial Sloan Kettering Cancer Center Sleepy Hollow	Sleepy Hollow	New York

Sponsors (4)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	Bayer, Queens Cancer Center of Queens Hospital, State University of New York - Downstate Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	progression free survival	Response and progression will be evaluated in this study using the international criteria proposed by the RECIST 1.1 Committee. Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are used in the RECIST criteria.	16 weeks
Secondary	overall survival	Overall survival is defined as the time from treatment start to death or last follow up. Survival will be estimated using the Kaplan-Meier method.	2 years
Secondary	disease control rate	Disease control rate (defined with RECIST 1.1 criteria at 16 weeks (2nd scan) as CR, PR or SD), will be estimated using proportions and exact binomial 95% confidence intervals provided.	16 weeks
Secondary	duration of stable disease	Duration of stable disease will be defined as the time from stable disease to the time of documented progression.	2 years
Secondary	toxicity	will be evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 4.0. The assessments will be based on recorded adverse events, physical examinations, and clinical laboratory assessments. Toxicity will be summarized using descriptive statistics.	2 years

External Links

•   Memorial Sloan Kettering Cancer Center