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

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ClinicalTrials.gov Identifier: NCT01871311
Recruitment Status : Terminated (Primary investigator left the institution.)
First Posted : June 6, 2013
Last Update Posted : February 8, 2019
Information provided by (Responsible Party):
Georgetown University

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.

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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

Resource links provided by the National Library of Medicine

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.

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

Information from the National Library of Medicine

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

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01871311

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United States, District of Columbia
Georgetown Lombardi Comprehensive Cancer Center
Washington, District of Columbia, United States, 20007
Sponsors and Collaborators
Georgetown University
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Principal Investigator: Ann W Gramza, MD Georgetown University
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Responsible Party: Georgetown University
ClinicalTrials.gov Identifier: NCT01871311    
Other Study ID Numbers: 2013-0039
First Posted: June 6, 2013    Key Record Dates
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
Additional relevant MeSH terms:
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Head and Neck Neoplasms
Neoplasms by Site
Antineoplastic Agents, Immunological
Antineoplastic Agents