Recurrent Adenoid Cystic Carcinoma of the Oral CavityPhase 1NCT01637194
Cetuximab and Everolimus in Treating Patients With Metastatic or Recurrent Colon Cancer or Head and Neck Cancer
A Phase 1 study testing everolimus, cetuximab and pharmacological study in people with Recurrent Adenoid Cystic Carcinoma of the Oral Cavity and Recurrent Basal Cell Carcinoma of the Lip, run by Fox Chase Cancer Center at 1 site in United States.
Trial summary
This phase I trial studies the side effects and best dose of cetuximab when given together with everolimus in treating patients with metastatic or recurrent colon cancer or head and neck cancer. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent Adenoid Cystic Carcinoma of the Oral Cavity, Recurrent Basal Cell Carcinoma of the Lip, Recurrent Colon Cancer
- What is being tested?
- everolimus, cetuximab and pharmacological study
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2008to Jul 2011
- 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
- Patients must have histologically-confirmed advanced solid tumors
- Patients who are refractory to standard therapy; patients with metastatic, irinotecan-refractory colon cancer, or recurrent/metastatic head and neck cancer may enroll, as cetuximab monotherapy is among the standard options for such patients; patients with locally advanced, treatment-naïve head and neck cancer who are candidates for radiation with cetuximab are not eligible, as radiation provides them a survival benefit, and the number of projected cetuximab doses would be only seven
- Development of new lesions or an increase in preexisting lesions on bone scintigraphy, computed tomography (CT), magnetic resonance imaging (MRI) or by physical examination; patients in whom the sole criterion for progression is an increase in a biochemical marker, e.g., carcinoembryonic antigen (CEA), or an increase in symptoms, are not eligible
- No radiotherapy (unless palliative), treatment with cytotoxic agents, or treatment with biologic agents =< 3 weeks prior to registration on this study (6 weeks for mitomycin or nitrosoureas); >= 2 weeks must have elapsed from any prior surgery or hormonal therapy; patients must have fully recovered from the acute toxicities of any prior treatment with cytotoxic drugs, radiotherapy or other anti-cancer modalities (returned to baseline status as noted before most recent treatment); patients with persisting, stable chronic toxicities from prior treatment =< grade 1 are eligible
- Eastern Cooperative Oncology Group (ECOG) performance status =<2 (Karnofsky >= 60%)
- Life expectancy of > 3 months
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- Hemoglobin >= 9 g/dL
- Leukocytes >=3 K/mm^3
- Absolute neutrophil count >= 1.5 K/mm^3
- Platelets >= 100 K/mm^3
- Total bilirubin within institutional normal limits
- Hepatitis B panel negative
- Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamic pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal (ULN)
- Creatinine within 1.5 x ULN OR creatinine clearance >= 50 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
- Women of child-bearing potential (WOCBP) must agree to use adequate contraception (hormonal or barrier method of birth control; complete abstinence) prior to study entry and for the duration of study participation and for 3 months after the conclusion of study therapy, and must have a negative serum or urine pregnancy test =< 7 days prior to registration; pregnant and nursing patients are excluded because the side effects of the combination of cetuximab and RAD001 on a fetus or nursing child are unknown; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; sexually active men must also use appropriate contraception method and should not father a child while receiving therapy during this study
- Ability to understand and the willingness to sign a written informed consent document
- Fasting serum cholesterol < 350 mg/d L and triglycerides < 400 mg/d L
- Able and willing to undergo pharmacokinetic (PK) and pharmacodynamic (PD) testing as outlined in this protocol; if however the tumor is not amenable to the PD requirements of the protocol, the patient must be willing and able to undergo skin biopsy
Who cannot join
- Chronic treatment with systemic steroids or another immunosuppressive agent
- Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases
- Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
- Patients with an active, bleeding diathesis or on therapeutic anticoagulation (except low dose coumadin)
- Patients may not have received prior cetuximab therapy
- Patients may not be receiving any other investigational agents; in addition, patients must not have received investigational treatment =< 30 days prior to registration
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- History of allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in study
- Patients with chronic active hepatitis B or recent hepatitis B infection (hepatitis B surface antigen [HepB sAg] or immunoglobulin M [IgM] antibody to hepatitis B core antigen [IgM antiBc] positive) are ineligible because these patients are at increased risk of reactivation of the hepatitis B virus which may be fatal due to the immunosuppressive properties of RAD001
- Known human immunodeficiency virus (HIV)-positive patients are ineligible because these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy and the potential pharmacokinetic interaction between antiretroviral therapy and the investigational agents
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, oxygen dependent pulmonary disease or psychiatric illness/social situations that would limit compliance with study requirements; other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study (i.e., uncontrolled diabetes, uncontrolled hypertension, severe malnutrition, active ischemic heart disease, myocardial infarction within six months, chronic liver or renal disease, active upper gastrointestinal [GI] tract ulceration)
- All WOCBP MUST have a negative pregnancy test =< 7 days prior to registration; if the pregnancy test is positive, the patient must not receive investigational product and must not be enrolled in the study
Trial locations and contacts
1 site in 1 country.
United States1 site
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111-2497
About this study
Official title: A Phase I Evaluation of Cetuximab and RAD001 in Patients With Solid Tumors
This phase I trial studies the side effects and best dose of cetuximab when given together with everolimus in treating patients with metastatic or recurrent colon cancer or head and neck cancer. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of the tumor to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Everolimus may stop the growth of tumor cells by blocking blood flow to the tumor. Giving cetuximab together with everolimus may be an effective treatment for colon cancer or head and neck cancer
Read the detailed description
PRIMARY OBJECTIVES:
- Determine the safety, dose-limiting toxicity and maximum tolerated dose of daily RAD001 (everolimus) when given in combination with a fixed dose of weekly cetuximab in patients with solid tumors.
SECONDARY OBJECTIVES:
- Determine whether a pharmacokinetic interaction exists between RAD001 and CETUXIMAB in patients treated with this regimen.
II. Determine preliminary clinical evidence of anti-tumor activity by time to progression and Response Evaluation Criteria in Solid Tumors (RECIST) criteria with this regimen.
III. Determine the association between clinical outcomes and biologic markers that may predict sensitivity of a tumor in patients treated with this regimen.
IV. Determine the pharmacodynamic effects of this regimen on post-therapy tumor and/or skin specimens.
OUTLINE: This is a dose-escalation study of everolimus.
Patients receive everolimus orally (PO) once daily (QD) on days -14 and then 1-28. Patients also receive cetuximab intravenously (IV) over 60-120 minutes on days -7 and then once weekly beginning on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 2 months for at least 1 year.
- Conditions
- Recurrent Adenoid Cystic Carcinoma of the Oral Cavity, Recurrent Basal Cell Carcinoma of the Lip, Recurrent Colon Cancer, Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity, Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity, Recurrent Lymphoepithelioma of the Nasopharynx
- Being tested
- everolimus, cetuximab, pharmacological study, laboratory biomarker analysis
- Medical subject headings
- Colonic Neoplasms, Esthesioneuroblastoma, Olfactory, Salivary Gland Neoplasms, Squamous Cell Carcinoma of Head and Neck, Tongue Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
everolimusDrug
Also called 42-O-(2-hydroxy)ethyl rapamycin, Afinitor, RAD001
Given PO
cetuximabBiological
Also called C225, C225 monoclonal antibody, IMC-C225, MOAB C225
Given IV
Also called pharmacological studies
Correlative studies
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (enzyme inhibitor, monoclonal antibody therapy) | Experimental | Patients receive everolimus PO QD on days -14 and then 1-28. Patients also receive cetuximab IV over 60-120 minutes on days -7 and then once weekly beginning on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: everolimus; Biological: cetuximab; Other: pharmacological study; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with dose limiting toxicity
Dose-limiting toxicity defined as any grade 3 or greater non-hematologic, grade 4 thrombocytopenia, grade 4 neutropenia lasting more than 5 days, grade 4 febrile neutropenia requiring hospitalization or treatment delay more than 2 weeks due to unresolved toxicity.
Measured: Day -14 through Day 28 of Cycle 1
Secondary outcomes (4)
Composite Pharmacokinetic (PK) Analysis
PKs derived from serum concentrations versus time for RAD001 on day -14, 1, and 22 at 1, 2, 3, 6, and 24 hours after drug administration as well as day -7 (h 168) and prior to dosing on Day 4.
Measured: At days -14, 1,and 22 at 1, 2, 3, 6, and 24 hours after drug treatment and day -7 and prior to dosing on day -4
Preliminary clinical evidence of anti-tumor activity by time to progression and RECIST criteria with this regimen
Measured: Baseline and every 2 courses (8 weeks)
Association between clinical outcomes and biologic markers that may predict sensitivity of a tumor in patients treated with this regimen
Measured: Baseline, 24 hours post-treatment on day 22
Pharmacodynamic effects of this regimen on post-therapy tumor and/or skin specimens
Measured: At baseline, 24 hours post-therapy on day 22
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2012 (estimated)
- Study startNov 2008
- Primary completionJul 2011
- Study completionJul 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent Adenoid Cystic Carcinoma of the Oral CavityStudies of the same condition, open and under way.
- More trials run by Fox Chase Cancer CenterThe 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
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fox Chase Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Barbara Burtness, Principal investigator, Fox Chase Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01637194
- Sponsor's protocol ID
- IRB 06-043
- Other IDs
- NCI-2011-02971
- Status last verified
- Jul 2012
- First submitted
- 20 Oct 2011
- Last updated
- 11 Jul 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 Jul 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Evaluation of Cetuximab and RAD001 in Patients With Solid Tumors
- ClinicalTrials.gov ID
- NCT01637194
- Acronym / sponsor ID
- IRB 06-043
- Conditions
- Recurrent Adenoid Cystic Carcinoma of the Oral Cavity, Recurrent Basal Cell Carcinoma of the Lip, Recurrent Colon Cancer, Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity, Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity, Recurrent Lymphoepithelioma of the Nasopharynx
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Fox Chase Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Nov 2008
- Primary completion
- Jul 2011 (actual)
- Study completion
- Jul 2011 (actual)
- First posted
- 11 Jul 2012 (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.
This phase I trial studies the side effects and best dose of cetuximab when given together with everolimus in treating patients with metastatic or recurrent colon cancer or head and neck cancer. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of the tumor to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Everolimus may stop the growth of tumor cells by blocking blood flow to the tumor. Giving cetuximab together with everolimus may be an effective treatment for colon cancer or head and neck cancer
Detailed description
PRIMARY OBJECTIVES:
- Determine the safety, dose-limiting toxicity and maximum tolerated dose of daily RAD001 (everolimus) when given in combination with a fixed dose of weekly cetuximab in patients with solid tumors.
SECONDARY OBJECTIVES:
- Determine whether a pharmacokinetic interaction exists between RAD001 and CETUXIMAB in patients treated with this regimen.
II. Determine preliminary clinical evidence of anti-tumor activity by time to progression and Response Evaluation Criteria in Solid Tumors (RECIST) criteria with this regimen.
III. Determine the association between clinical outcomes and biologic markers that may predict sensitivity of a tumor in patients treated with this regimen.
IV. Determine the pharmacodynamic effects of this regimen on post-therapy tumor and/or skin specimens.
OUTLINE: This is a dose-escalation study of everolimus.
Patients receive everolimus orally (PO) once daily (QD) on days -14 and then 1-28. Patients also receive cetuximab intravenously (IV) over 60-120 minutes on days -7 and then once weekly beginning on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 2 months for at least 1 year.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (enzyme inhibitor, monoclonal antibody therapy) | Experimental | Drug: everolimus, Biological: cetuximab, Other: pharmacological study, Other: laboratory biomarker analysisPatients receive everolimus PO QD on days -14 and then 1-28. Patients also receive cetuximab IV over 60-120 minutes on days -7 and then once weekly beginning on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Patients must have histologically-confirmed advanced solid tumors
- Patients who are refractory to standard therapy; patients with metastatic, irinotecan-refractory colon cancer, or recurrent/metastatic head and neck cancer may enroll, as cetuximab monotherapy is among the standard options for such patients; patients with locally advanced, treatment-naïve head and neck cancer who are candidates for radiation with cetuximab are not eligible, as radiation provides them a survival benefit, and the number of projected cetuximab doses would be only seven
- Development of new lesions or an increase in preexisting lesions on bone scintigraphy, computed tomography (CT), magnetic resonance imaging (MRI) or by physical examination; patients in whom the sole criterion for progression is an increase in a biochemical marker, e.g., carcinoembryonic antigen (CEA), or an increase in symptoms, are not eligible
- No radiotherapy (unless palliative), treatment with cytotoxic agents, or treatment with biologic agents =< 3 weeks prior to registration on this study (6 weeks for mitomycin or nitrosoureas); >= 2 weeks must have elapsed from any prior surgery or hormonal therapy; patients must have fully recovered from the acute toxicities of any prior treatment with cytotoxic drugs, radiotherapy or other anti-cancer modalities (returned to baseline status as noted before most recent treatment); patients with persisting, stable chronic toxicities from prior treatment =< grade 1 are eligible
- Eastern Cooperative Oncology Group (ECOG) performance status =<2 (Karnofsky >= 60%)
Key exclusion criteria (11 listed)
- Chronic treatment with systemic steroids or another immunosuppressive agent
- Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases
- Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
- Patients with an active, bleeding diathesis or on therapeutic anticoagulation (except low dose coumadin)
- Patients may not have received prior cetuximab therapy
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 |
|---|---|---|
| everolimusAlso: 42-O-(2-hydroxy)ethyl rapamycin, Afinitor, RAD001Given PO | Drug | Treatment (enzyme inhibitor, monoclonal antibody therapy) |
| cetuximabAlso: C225, C225 monoclonal antibody, IMC-C225, MOAB C225Given IV | Biological | Treatment (enzyme inhibitor, monoclonal antibody therapy) |
| pharmacological studyAlso: pharmacological studiesCorrelative studies | Other | Treatment (enzyme inhibitor, monoclonal antibody therapy) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (enzyme inhibitor, monoclonal antibody therapy) |
Primary outcome
Number of patients with dose limiting toxicity
Time frame: Day -14 through Day 28 of Cycle 1
Dose-limiting toxicity defined as any grade 3 or greater non-hematologic, grade 4 thrombocytopenia, grade 4 neutropenia lasting more than 5 days, grade 4 febrile neutropenia requiring hospitalization or treatment delay more than 2 weeks due to unresolved toxicity.
4 secondary outcomes
Composite Pharmacokinetic (PK) Analysis
Time frame: At days -14, 1,and 22 at 1, 2, 3, 6, and 24 hours after drug treatment and day -7 and prior to dosing on day -4
Preliminary clinical evidence of anti-tumor activity by time to progression and RECIST criteria with this regimen
Time frame: Baseline and every 2 courses (8 weeks)
Association between clinical outcomes and biologic markers that may predict sensitivity of a tumor in patients treated with this regimen
Time frame: Baseline, 24 hours post-treatment on day 22
Pharmacodynamic effects of this regimen on post-therapy tumor and/or skin specimens
Time frame: At baseline, 24 hours post-therapy on day 22
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jul 2012.
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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.
Barbara Burtness principal investigator
Fox Chase Cancer Center
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 everolimus, cetuximab and pharmacological study in people with Recurrent Adenoid Cystic Carcinoma of the Oral Cavity and Recurrent Basal Cell Carcinoma of the Lip, run by Fox Chase Cancer Center 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 18 inclusion and 11 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: finished, as of the sponsor's last update on 11 Jul 2012. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Number of patients with dose limiting toxicity (time frame: Day -14 through Day 28 of Cycle 1). 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 11 Jul 2012.