Phase 2
N=123
Lower or Standard Dose Regorafenib in Treating Patients With Refractory Metastatic Colorectal Cancer
Colon Adenocarcinoma · Rectal Adenocarcinoma · Stage III Colorectal Cancer AJCC v7 · Stage IIIA Colorectal Cancer AJCC v7 · Stage IIIB Colorectal Cancer AJCC v7
Bottom Line
View on ClinicalTrials.gov: NCT02368886 ↗Enrolled (actual)
123
Serious AEs
29.1%
Results posted
Jul 2019
Primary outcome: Primary: Proportion of Patients in Each Arm Who Complete 2 Cycles of Protocol Treatment and Initiate Cycle 3 — 0.43; 0.26 proportion of patients — p=0.0434
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Clobetasol Propionate (Drug); Pharmacological Study (Other); Quality-of-Life Assessment (Other); Regorafenib (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Academic and Community Cancer Research United
- Primary completion
- Sep 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Proportion of Patients in Each Arm Who Complete 2 Cycles of Protocol Treatment and Initiate Cycle 3 |
0.43; 0.26 | 0.0434 sig |
| SECONDARY Overall Survival (OS) |
9.8; 6.0 | 0.1241 |
| SECONDARY Progression Free Survival (PFS) |
2.8; 2.0 | 0.3797 |
| SECONDARY Time to Progression (TTP) |
2.8; 2.0 | 0.4614 |
| SECONDARY Cumulative (Total) Dose of Regorafenib Received by Patients in the First Two Cycles |
91.8; 133.1; 121.3; 117.3 | — |
| SECONDARY Dose Intensity of Regorafenib Received by Patients in the First Two Cycles as Measured by the Percentage of Planned Dose Received |
76.2; 76.0 | — |
| SECONDARY Proportion of Patients Overall and Within Each Arm Experiencing Grade 3 or 4 Hand and Foot Syndrome (HFS) |
0.1786; 0.1154; 0.1515; 0.1724 | — |
| SECONDARY Quality of Life (QOL) (According to the HFS14 Total Score) |
20.8; 29.5; 15.8; 21.8 | — |
| SECONDARY Changes in QOL (According to the Linear Analogue Self-Assessment [LASA] Questionnaire) |
-0.9; -0.3; -0.7; -0.9 | 0.7319 |
Summary
This randomized phase II trial studies how well lower-dose compared to standard dose regorafenib works in treating patients with colorectal cancer that has spread from the primary site (place where it started) to other places in the body and does not respond to treatment. Regorafenib may stop the growth of colorectal cancer by blocking the growth of new blood vessels necessary for tumor growth and by blocking some of the enzymes needed for cell growth. It is not yet known whether lower-dose or standard dose regorafenib is more effective in treating patients with colorectal cancer. Clobetasol propionate is a steroid cream that is commonly used to treat a variety of skin conditions and may help prevent hand-foot skin reactions in patients receiving regorafenib.
Eligibility Criteria
Inclusion Criteria
- Histological or cytological documentation of adenocarcinoma of the colon or rectum
- Advanced or metastatic colorectal cancer with no curative options available and progression on previous standard therapy, including an EGFR inhibitor if KRAS wild-type
- Measurable or non-measurable disease
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
- Life expectancy of >= 3 months
- Absolute neutrophil count (ANC) > 1500/mm^3 (obtained = 100,000/mm^3 (obtained = 9.0 g/dL (obtained = New York Heart Association (NYHA) class 2
- Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months) or myocardial infarction less than 6 months prior to randomization
- Cardiac arrhythmias requiring anti-arrhythmic therapy; Note: pace makers, beta blockers, or digoxin are permitted
- Uncontrolled hypertension; (systolic blood pressure > 140 mmHg or diastolic pressure > 90 mmHg despite optimal medical management)
- History of or current pheochromocytoma
- Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism = grade 2 National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
- 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 randomization and is clinically stable with respect to the tumor at the time of randomization; note: 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 (including corneal transplant)
- Evidence or history of bleeding diathesis or any hemorrhage or bleeding event > CTCAE grade 3 = = 1
- Substance abuse, medical, psychological or social conditions that may interfere with the patient?s participation in the study or evaluation of the study results
- Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation
- Interstitial lung disease with ongoing signs and symptoms at the time of informed consent
- Persistent proteinuria of Common Toxicity Criteria (CTC) grade 3 or higher (>= 3.5 g/24 hours [hrs])
- Patients unable to swallow oral medications
- Any malabsorption condition
- Unresolved toxicity greater than CTCAE (version 4.0) grade 1 attributed to any prior therapy/procedure excluding alopecia and oxaliplatin induced neurotoxicity = = CTCAE version 4.0 grade 2 dyspnea)
- Concurrent anti-cancer therapy =< 4 weeks from registration (chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, or tumor embolization)
- Current use of clobetasol propionate
- Use of any herbal remedy (e.g. St. John?s wort [Hypericum perforatum])
- Patients unable to ambulate or who have amputations or paralysis of any extremity
- History of contact dermatitis to clobetasol propionate or similarly fluorinated steroids or other steroids with the propionate ester
Data sourced from ClinicalTrials.gov (NCT02368886). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.