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

Tracking Information

• First Submitted Date: June 4, 2013
• First Posted Date: June 6, 2013
• Last Update Posted Date: February 8, 2019
• Study Start Date: May 2014
• Actual Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 4, 2013)

Maximum tolerated dose [ Time Frame: 18 months ]

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

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Phase I Study of Nilontinib and Cetuximab in Patients With Solid Tumors
• 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Colorectal Cancer
• Head and Neck Cancer

Intervention

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.

Study Arms

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

Intervention: Drug: Nilotinib + Cetuximab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: February 6, 2019): 15
• Original Estimated Enrollment (submitted: June 4, 2013): 22
• Actual Study Completion Date: December 2016
• Actual Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01871311
• Other Study ID Numbers: 2013-0039
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Georgetown University
• Original Responsible Party: Same as current
• Current Study Sponsor: Georgetown University
• Original Study Sponsor: Same as current
• Collaborators: Novartis

Investigators

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

• PRS Account: Georgetown University
• Verification Date: February 2019