Colorectal CancerPhase 1NCT01871311
A Phase I Study of Nilontinib and Cetuximab in Patients With Solid Tumors
A Phase 1 study testing Nilotinib + Cetuximab in people with Colorectal Cancer and Head and Neck Cancer, run by Georgetown University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer, Head and Neck Cancer
- What is being tested?
- Nilotinib + Cetuximab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- May 2014to Dec 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
- ECOG performance status
- Normal left ventricular ejection fraction, defined as EF > 50%
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Georgetown Lombardi Comprehensive Cancer Center
Washington D.C., District of Columbia, 20007
About this study
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
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.
Read the 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
- Being tested
- Nilotinib + Cetuximab
- Keywords
- metastatic Kras wildtype, squamous cell carcinoma, cetuximab, nilotinib
- Medical subject headings
- Colorectal Neoplasms, Head and Neck Neoplasms, Carcinoma, Squamous Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nilotinib + CetuximabDrug
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 group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Nilotinib + Cetuximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose
The dose at which </= 1 out of 6 subjects experiences a dose limiting toxicity
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2013 (estimated)
- Study startMay 2014
- Primary completionDec 2016
- Study completionDec 2016
Why it stopped: Primary investigator left the institution.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Georgetown UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Georgetown University
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Sponsor
- Investigators
- Ann W Gramza, MD, Principal investigator, Georgetown University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01871311
- Sponsor's protocol ID
- 2013-0039
- Status last verified
- Feb 2019
- First submitted
- 4 Jun 2013
- Last updated
- 8 Feb 2019
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01871311
- Acronym / sponsor ID
- 2013-0039
- Conditions
- Colorectal Cancer, Head and Neck Cancer
- Keywords
- metastatic Kras wildtype, squamous cell carcinoma, cetuximab, nilotinib
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Primary investigator left the institution.
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Georgetown UniversityUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- May 2014
- Primary completion
- Dec 2016 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 6 Jun 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Nilotinib + Cetuximab | Experimental | Drug: Nilotinib + CetuximabAll patients with receive Nilotinib BID for a 28-day cycle + Cetuximab 400 mg/m2 on day 1 dose then 250 mg/m2 weekly |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Recurrent and/or metastatic Kras wildtype colorectal cancer or squamous cell carcinoma of the head and neck
- Previous therapy:
- 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.
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nilotinib + CetuximabNilotinib 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. | Drug | Nilotinib + Cetuximab |
Primary outcome
Maximum tolerated dose
Time frame: 18 months
The dose at which </= 1 out of 6 subjects experiences a dose limiting toxicity
Results and safety
The study was stopped early (reason given: Primary investigator left the institution.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2019.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ann W Gramza, MD principal investigator
Georgetown University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Nilotinib + Cetuximab in people with Colorectal Cancer and Head and Neck Cancer, run by Georgetown University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 8 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Primary investigator left the institution.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose (time frame: 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Feb 2019.