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

NCT ID: NCT01871311

Last Updated: 2019-02-08

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-05-31
• Study Completion Date: 2016-12-31

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.

Detailed Description

ABL1 has been suggested to play a key role in the resistance mechanism to anti EGFR therapy in cancer. Therefore, this study aims to evaluate the safety and possible effect of targeting both EGFR using cetuximab along with ABL1 using nilotinib. Correlative studies assess the changes in tumor proteome in response to therapy and magnitude of ADCC as a marker of antibody activity.

Conditions

Colorectal Cancer; Head and Neck Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Nilotinib + Cetuximab

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

Group Type: EXPERIMENTAL

Nilotinib + Cetuximab

Intervention Type: 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.

Interventions

Nilotinib + Cetuximab

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Recurrent and/or metastatic Kras wildtype colorectal cancer or squamous cell carcinoma of the head and neck

2. Previous therapy:

1. 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.

2. Patients may have received cetuximab or panitumumab previously

3. Ability to swallow medication tablets by mouth (which may include taking nilotinib mixed in apple sauce)

4. At least one measurable lesion by RECIST criteria

5. A tumor lesion that can be readily biopsied using a core needle via clinical exam or image-guidance.

6. Over the age of 18 years and able to provide informed consent

7. Adequate kidney, liver, and bone marrow function as follows:

1. Hemoglobin >/= 8.0 gm/dL

2. Absolute neutrophil count >/= 1500

3. Platelet count >/= 100,000

4. Creatinine within institutional normal limits or glomerular filtration rate > 60

5. Total bilirubin f. AST and ALT

8. Life expectancy of greater than 3 months

9. ECOG performance status

10. Normal left ventricular ejection fraction, defined as EF > 50%

Exclusion Criteria

1. Chemotherapy or surgery within 4 weeks prior to treatment start

2. Radiation treatment within 3 weeks prior to treatment start

3. Prior therapy with nilotinib, ponatinib, dasatinib, or imatinib

4. 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

5. 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

6. Diarrhea > Grade 1 at baseline

7. Concomitant medication or herbal therapy known to inhibit CYP3A4

8. 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

9. Ongoing ventricular cardiac dysrhythmias of NCI CTCAE grade >/= 2

10. Subjects with a history of serious ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation >/= 3 beats in a row)

11. Serious cardiac arrhythmia requiring medication

12. QTc interval > 500 msec

13. 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

14. Patients unwilling or unable to comply with the protocol, or provide informed consent

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis

INDUSTRY

Sponsor Role: collaborator

Georgetown University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ann W Gramza, MD

Role: PRINCIPAL_INVESTIGATOR

Georgetown University

Locations

Georgetown Lombardi Comprehensive Cancer Center

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

Countries

United States

Other Identifiers

2013-0039

Identifier Type: -

Identifier Source: org_study_id