Regorafenib and Cetuximab in Patients With Advanced Malignancy

NCT02095054 | Completed Phase 1 FDA Drug

• 2 other identifiers: 2013-0833NCI-2014-01307
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to find the highest tolerable dose of the combination of regorafenib and cetuximab that can be given to patients with advanced solid tumors. The safety and effectiveness of this drug combination will also be studied.

Conditions

Advanced Cancers

Keywords

Advanced Cancers; Advanced malignancy; Metastatic cancer; Advanced solid tumor; Regorafenib; Stivarga; Cetuximab; C225; Erbitux; IMC-C225; MOAB C225; Questionnaire; Survey

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of Treatment with Regorafenib and Cetuximab

  MTD defined by dose limiting toxicities (DLTs) that occur in the first cycle (four weeks), determined as the highest dose studied in which the incidence of DLT is less than 33%. DLT defined as any grade 3 or 4 non-hematologic toxicity related to study medication(s) (except nausea and vomiting responsive to appropriate regimens, alopecia, or correctable electrolyte imbalances), any Grade 4 hematologic toxicity lasting 2 weeks or longer (as defined by NCI-CTCAE) despite supportive care; any Grade 4 nausea or vomiting \> 5 days despite maximum anti-nausea regimens; or any severe or life-threatening complication or abnormality not defined in NCI-CTCAE that is attributable to therapy.

  4 weeks

Secondary Outcomes (2)

• Tumor Response of Treatment with Regorafenib and Cetuximab by RECIST Criteria

  4 months

• Tumor Response of Treatment with Regorafenib and Cetuximab by WHO Criteria

  4 months

Study Arms (1)

Regorafenib + Cetuximab

EXPERIMENTAL

Dose Escalation Group Starting Dose of Regorafenib: 80 mg by mouth once a day for 21 days (5 days on and 2 days off) in a 28 days cycle. Dose Expansion Group Starting Dose of Regorafenib : MTD from Dose Escalation Group. Dose Escalation Group Starting Dose of Cetuximab: 200 mg/m2 initial dose, then 150 mg/m2 by vein over about 1-2 hours on Days 1, 8, 15, and 22 of each 28 day cycle. Dose Expansion Group Starting Dose of Cetuximab: MTD from Dose Escalation Group. Symptom questionnaire completed at each study visit.

Drug: Regorafenib; Drug: Cetuximab; Behavioral: Questionnaire

Interventions

Regorafenib DRUG

Dose Escalation Group Starting Dose of Regorafenib: 80 mg by mouth once a day for 21 days (5 days on and 2 days off) in a 28 days cycle. Dose Expansion Group Starting Dose of Regorafenib : MTD from Dose Escalation Group.

Also known as: Stivarga

Regorafenib + Cetuximab

Cetuximab DRUG

Dose Escalation Group Starting Dose of Cetuximab: 200 mg/m2 initial dose, then 150 mg/m2 by vein over about 1-2 hours on Days 1, 8, 15, and 22 of each 28 day cycle. Dose Expansion Group Starting Dose of Cetuximab: MTD from Dose Escalation Group.

Also known as: C225, Erbitux, IMC-C225, MOAB C225

Regorafenib + Cetuximab

Questionnaire BEHAVIORAL

Symptom questionnaire completed at each study visit.

Also known as: Survey

Regorafenib + Cetuximab

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient must be \>= 12 years of age and \> 40kgs.
• Patients with advanced or metastatic cancer that is refractory to standard therapy, relapsed after standard therapy, or have no standard therapy that induces a CR rate of at least 10% or improves survival by at least three months.
• Patients must have evaluable or measurable disease by RECIST criteria for solid tumors.
• Ability to understand and the willingness to sign a written informed consent document.
• Patients must be \>/= 4 weeks beyond treatment with any chemotherapy or radiotherapy, and must have recovered to \</= grade 2 toxicity for any treatment-limiting toxicity of prior therapy. (Exception: patients may have received palliative low dose radiotherapy to the limbs 1-4 weeks before this therapy provided pelvis, ribs, sternum, scapulae, vertebrae or skull were not included in the radiotherapy field). Also, patients who have received non-chemotherapeutic biologic agents will need to wait at least five half-lives or four weeks, whichever is shorter, from the last day of treatment. Exception: No washout of cetuximab or regorafenib is required for patients who have received prior cetuximab or regorafenib and have recovered from any treatment-related toxicities to Grade \</= 1.
• ECOG performance status \</= 2 (Karnofsky \>/= 60%).
• Patients must have: leukocytes \>/= 3,000/mL; absolute neutrophil count \>/= 1,000/mL; platelets \>/=100,000/mL; creatinine \</= 2 X ULN; total bilirubin \</= 2.0; ALT(SGPT) \</= 3 X ULN; Exception for patients with liver metastasis: total bilirubin \</= 3 x ULN; AST (SGOT) and ALT(SGPT) \</= 5 X ULN. Patients should not have received any platelet transfusions in the last 4 weeks before screening date.
• Patients should not become pregnant or breastfeed while on this study. Sexually active patients must agree to use contraception prior to study entry, for the duration of study participation, and for 30 days after the last dose.

You may not qualify if:

• KRAS mutated colorectal cancer.
• Major surgery within 28 days prior to the first dose of study medication.
• Pregnant or lactating women.
• Patients with hemoptysis within 28 days prior to entering the study.
• Patients with clinically significant unexplained bleeding within 28 days prior to entering the study.
• Uncontrolled systemic vascular hypertension (Systolic blood pressure \> 140 mmHg, diastolic blood pressure \> 90 mmHg on medication).
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics on Day 1.
• Patients with clinically significant cardiovascular disease: 1). History of CVA within 6 months; 2). Myocardial infarction or unstable angina within 6 months; 3). Unstable angina pectoris; 4). New York Heart Association Class III or greater congestive heart failure.
• Patients with untreated or progressing brain metastases.
• Patients who had radiation to greater than 25% marrow in the past 5 years.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Subbiah V, Khawaja MR, Hong DS, Amini B, Yungfang J, Liu H, Johnson A, Schrock AB, Ali SM, Sun JX, Fabrizio D, Piha-Paul S, Fu S, Tsimberidou AM, Naing A, Janku F, Karp DD, Overman M, Eng C, Kopetz S, Meric-Bernstam F, Falchook GS. First-in-human trial of multikinase VEGF inhibitor regorafenib and anti-EGFR antibody cetuximab in advanced cancer patients. JCI Insight. 2017 Apr 20;2(8):e90380. doi: 10.1172/jci.insight.90380. eCollection 2017 Apr 20.

  PMID: 28422758 DERIVED

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

regorafenib; Cetuximab; Surveys and Questionnaires

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Data Collection; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Officials

• Vivek Subbiah, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2014
• First Posted: March 24, 2014
• Study Start: March 19, 2014
• Primary Completion: March 27, 2020
• Study Completion: March 27, 2020
• Last Updated: April 1, 2021

Record last verified: 2021-03

Locations

US (1)