A Phase I Study of Nilontinib and Cetuximab in Patients With Solid Tumors

NCT01871311 | Terminated Phase 1 DMC

• 1 other identifier: 2013-0039
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the recommended Phase II dose of nilotinib when used in combination with cetuximab in the treatment of patients with recurrent and/or metastatic Kras wildtype colorectal cancer or squamous cell carcinoma of the head and neck.

Conditions

Colorectal Cancer; Head and Neck Cancer

Keywords

metastatic Kras wildtype; squamous cell carcinoma; cetuximab; nilotinib

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose

  The dose at which \</= 1 out of 6 subjects experiences a dose limiting toxicity

  18 months

Study Arms (1)

Nilotinib + Cetuximab

EXPERIMENTAL

All patients with receive Nilotinib BID for a 28-day cycle + Cetuximab 400 mg/m2 on day 1 dose then 250 mg/m2 weekly

Drug: Nilotinib + Cetuximab

Interventions

Nilotinib + Cetuximab DRUG

Nilotinib BID for a 28-day cycle + Cetuximab 400 mg/m2 on day 1 dose then 250 mg/m2 weekly Three dose levels for nilotinib: Dose level -1 200-mg daily Dose level 1 200-mg BID Dose level 2 300-mg BID Cycle duration will be 4 weeks, with weekly evaluation of toxicity. Assessment of tumor progression will occur every 2 cycles. Subjects will be treated until disease progression or cessation due to intolerable toxicity.

Nilotinib + Cetuximab

Eligibility Criteria

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

You may qualify if:

• Recurrent and/or metastatic Kras wildtype colorectal cancer or squamous cell carcinoma of the head and neck
• Previous therapy:
• Patients must have progressed after standard therapy for metastatic/recurrent disease, including irinotecan and oxaliplatin-containing regimens for patients with CRC and platinum-containing regimens for patients with H\&NSCC.
• Patients may have received cetuximab or panitumumab previously
• Ability to swallow medication tablets by mouth (which may include taking nilotinib mixed in apple sauce)
• At least one measurable lesion by RECIST criteria
• A tumor lesion that can be readily biopsied using a core needle via clinical exam or image-guidance.
• Over the age of 18 years and able to provide informed consent
• Adequate kidney, liver, and bone marrow function as follows:
• Hemoglobin \>/= 8.0 gm/dL
• Absolute neutrophil count \>/= 1500
• Platelet count \>/= 100,000
• Creatinine within institutional normal limits or glomerular filtration rate \> 60
• Total bilirubin f. AST and ALT
• Life expectancy of greater than 3 months

You may not qualify if:

• Chemotherapy or surgery within 4 weeks prior to treatment start
• Radiation treatment within 3 weeks prior to treatment start
• Prior therapy with nilotinib, ponatinib, dasatinib, or imatinib
• Untreated brain metastases or neurologically unstable central nervous system metastases; CNS metastases will be considered stable if there is no new nor enlarging lesions for one month, and the patient remains off steroids and anti-epileptics for the same time period
• Any severe or uncontrolled medical condition or other condition that could affect participation in this study, including: unstable angina, uncontrolled hypertension, serious uncontrolled cardiac arrhythmia, uncontrolled infection, or myocardial infarction
• Diarrhea \> Grade 1 at baseline
• Concomitant medication or herbal therapy known to inhibit CYP3A4
• Gastrointestinal tract disease resulting in the inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease
• Ongoing ventricular cardiac dysrhythmias of NCI CTCAE grade \>/= 2
• Subjects with a history of serious ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation \>/= 3 beats in a row)
• Serious cardiac arrhythmia requiring medication
• QTc interval \> 500 msec
• Female patients who are pregnant or breast feeding, or adults who are of reproductive potential and are unwilling to refrain from conceiving a child during study treatment
• Patients unwilling or unable to comply with the protocol, or provide informed consent

Sponsors & Collaborators

• Georgetown University: lead
• Novartis: collaborator

Study Sites (1)

Georgetown Lombardi Comprehensive Cancer Center

Washington D.C., District of Columbia, 20007, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Head and Neck Neoplasms; Carcinoma, Squamous Cell

Interventions

nilotinib; Cetuximab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Squamous Cell

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Ann W Gramza, MD

  Georgetown University

  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: June 4, 2013
• First Posted: June 6, 2013
• Study Start: May 1, 2014
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: February 8, 2019

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)