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

• ClinicalTrials.gov Identifier: NCT01871311
• Recruitment Status: Terminated
• First Posted: June 6, 2013
• Last Update Posted: February 8, 2019
• Sponsor: Georgetown University
• Collaborator: Novartis
• Information provided by (Responsible Party): Georgetown University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Colorectal Cancer; Head and Neck Cancer	Drug: Nilotinib + Cetuximab	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I Study of the BCR-ABL Tyrosine Kinase Inhibitor Nilontinib and Cetuximab in Patients With Solid Tumors That Can be Treated With Cetuximab
• Study Start Date: May 2014
• Actual Primary Completion Date: December 2016
• Actual Study Completion Date: December 2016

Arms and Interventions

Arm

Intervention/treatment

Experimental: 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

Drug: 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.

Outcome Measures

Primary Outcome Measures :

1. Maximum tolerated dose [ Time Frame: 18 months ]
   The dose at which </= 1 out of 6 subjects experiences a dose limiting toxicity

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, District of Columbia

Georgetown Lombardi Comprehensive Cancer Center

Washington, District of Columbia, United States, 20007

Sponsors and Collaborators

Georgetown University

Novartis

Investigators

• Principal Investigator: Ann W Gramza, MD; Georgetown University

More Information

• Responsible Party: Georgetown University
• ClinicalTrials.gov Identifier: NCT01871311
• Other Study ID Numbers: 2013-0039
• First Posted: June 6, 2013
• Last Update Posted: February 8, 2019
• Last Verified: February 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Georgetown University:

metastatic Kras wildtype; squamous cell carcinoma; cetuximab; nilotinib

Additional relevant MeSH terms:

Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Cetuximab; Antineoplastic Agents, Immunological; Antineoplastic Agents