Advanced, Malignant Aerodigestive Tract Tumor (Lung, Head and Neck and Esophagus)Phase 1NCT01116622
Erlotinib (Tarceva) and Bexarotene (Targretin) Oral Capsules in Advanced Cancers of the Aerodigestive Tract
A Phase 1 study testing Bexarotene (Targretin®) and Erlotinib (Tarceva™) in people with Advanced, Malignant Aerodigestive Tract Tumor (Lung, Head and Neck and Esophagus), run by Dartmouth-Hitchcock Medical Center at 1 site in United States.
Trial summary
Primary objective: To determine the Phase II doses and to evaluate the safety of administering bexarotene (Targretin®) daily in combination with oral erlotinib (Tarceva™) to patients with advanced aerodigestive tract cancers. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced, Malignant Aerodigestive Tract Tumor (Lung, Head and Neck and Esophagus)
- What is being tested?
- Bexarotene (Targretin®) and Erlotinib (Tarceva™)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2003to Apr 2014
- 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
- Pathological confirmation of advanced malignant aerodigestive tract tumo(lung, head and neck and esophagus)
- No known curative treatment.
- Age >18 years
- Karnofsky performance status ≥ 60%.
- Prior chemotherapy or radiotherapy is allowed.
- Fasting triglycerides equal or less than upper limit of normal
- Female patients and male patients with female partners of childbearing potential must agree to sexual abstinence or to practice effective contraception (recommended to be two reliable forms of non-hormonal contraception used simultaneously) during the entire period of Targretin capsule treatment and for at least one (1) month after treatment is discontinued. Male patients with female sexual partners who are pregnant, or possibly pregnant or who could become pregnant during the study must agree to use condoms during sexual intercourse during the entire period of Targretin capsule treatment and for at least one (1) month after the last dose of Targretin capsules.
- All patients must give informed consent indicating they are aware of the investigational nature of this treatment.
Who cannot join
- Organ dysfunction that precludes use of bexarotene or erlotinib:
- hepatic dysfunction, as evidenced by either:
- transaminase (SGOT or SGPT) > 2.5 X upper limit of normal (ULN) or > 5 X ULN if known liver metastases
- bilirubin > upper limit of normal
- renal dysfunction, as evidenced by calculated creatinine clearance < 30 ml/min
- A serious uncontrolled medical disorder or active infection which would impair their ability to receive study treatment will be excluded.
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- Significant cardiac disease, including uncontrolled high blood pressure, unstable angina, congestive heart failure, myocardial infarction within the previous 3 months or serious cardiac arrhythmias will be excluded. Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol will be excluded.
- Concurrent use of other anti-cancer investigational agents is not allowed
- Women who are pregnant or breast-feeding and women of childbearing potential or fertile males not using an adequate method of birth control will be excluded.
- Known hypersensitivity to bexarotene, erlotinib or other components of the capsules.
- Risk factor for pancreatitis (e.g., prior pancreatitis, uncontrolled hyperlipidemia,excessive alcohol consumption, uncontrolled diabetes mellitus, biliary tract 10 disease, and medications known to increase triglyceride levels or to be associated with pancreatic toxicity).
- Systemic anticancer therapy of any kind within 14 days prior to initiating study medications.
- Investigational therapy of any kind within 30 days prior to initiating study medications.
- Systemic vitamin A in doses exceeding 15,000 IU/day within 14 days prior to initiating study medications.
- Unwillingness or inability to minimize exposure to sunlight and artificial ultraviolet light while receiving the capsules.
Trial locations and contacts
1 site in 1 country.
United States1 site
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, 03756
About this study
Official title: A Phase I Clinical Study of Erlotinib (Tarceva) and Bexarotene (Targretin) Oral Capsules in Advanced Cancers of the Aerodigestive Tract
Primary objective: To determine the Phase II doses and to evaluate the safety of administering bexarotene (Targretin®) daily in combination with oral erlotinib (Tarceva™) to patients with advanced aerodigestive tract cancers.
Secondary objectives: To evaluate the response rates, progression-free survival and overall survival of patients with advanced aerodigestive tract cancers treated with bexarotene (Targretin®) in combination with erlotinib (Tarceva™). To investigate the activity of this targeted combination therapy by evaluating changes in molecular markers from pre- and post-treatment buccal swab samples.
Read the detailed description
This is a single institution open label dose-ranging trial. Consecutive, eligible patients presenting with the diagnosis of advanced aerodigestive tract malignancy are to be enrolled in this study. All eligible patients will receive continuous daily oral erlotinib (Tarceva™) with daily bexarotene oral capsules (Targretin®). The two agents will be taken at the same time. Three dose levels of daily bexarotene in combination with daily erlotinib will be studied.
Eligible patients will be entered in cohorts of three at each dose level. Doses will not be escalated over the course of treatment of an individual patient. If a single patient experiences grade 4 hematologic or ≥ grade 3 non-hematologic toxicity (excluding hyperlipidemia and nausea/vomiting), the next group of three patients will be entered at the same dose. A maximum of 6 evaluable patients will be enrolled at any one dose level. Dose escalation is performed after all patients (3 or 6) at the previous dose level have received treatment for 4 weeks. Treatment will continue until progression of disease, unacceptable adverse effects, or patient refusal. If grade 4 hematologic or ≥ grade 3 non-hematologic toxicity (excluding hyperlipidemia and nausea/vomiting) is observed in two or more patients on dose level 1, the next three patients (or six if similar toxicity develops in one of the first three patients) will receive dose level -1. If such toxicity is seen in two or more patients, the trial will be terminated. We anticipate the maximum accrual of 18 patients to this trial.
- Being tested
- Bexarotene (Targretin®), Erlotinib (Tarceva™)
- Keywords
- Aerodigestive, Targretin, Tarceva
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bexarotene (Targretin®)Drug
Also called Targetin, LGD1069
Level -I 200 mg/m2 Level I 300 mg/m2 Level II 300 mg/m2 Level III 400 mg/m2
Erlotinib (Tarceva™)Drug
Level -1 100mg Level I 100mg Level II 150mg Level III 150mg
| Study group | Role | What they receive |
|---|---|---|
| Daily oral erlotinib and bexarotene capusles | Experimental | Open label dose-ranging trial Receives: Drug: Bexarotene (Targretin®); Drug: Erlotinib (Tarceva™) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase II dose determination and evaluation of the safety of administering bexarotene(Targretin®) daily in combination with oral erlotinib (Tarceva™) to patients with advanced aerodigestive tract cancers.
The purpose of this study is to evaluate the safety of daily oral administration of bexarotene in combination with erlotinib at three dose levels to patients with advanced aerodigestive tract cancer. At least 3 patients will be entered onto each dose level. Dose limiting toxicity is defined as grade 3 or greater non-hematologic toxicity or grade 4 hematologic toxicity. The recommended Phase II dose is defined as the highest dose level of bexarotene oral capsules in combination with oral erlotinib that induces DLT in fewer than 33% of patients.
Measured: When final patient is removed from study or at the discreation of the investigator
Secondary outcomes (2)
Response rates, progression-free survival and overall survival of patients with advanced aerodigestive
Response rates will be described using RECIST criteria wherever possible. Survival will be determined by the number of days from study entry until death or date of last known followup and will be analyzed using the Kaplan-Meier method. Time to progression is defined as the interval from the initiation of treatment to the occurrence of progression or to last contact, or to the start of other antitumor therapy.
Measured: When final patient is removed from study or at the discretion of the investigator
Investigate the activity of this targeted combination therapy by evaluating changes in molecular markers from pre- and post-treatment buccal swab samples.
Measured: When final patient is removed from study or at the discretion of the investigator
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 May 2010 (estimated)
- Study startApr 2003
- Primary completionApr 2014
- Study completionApr 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced, Malignant Aerodigestive Tract Tumor (Lung, Head and Neck and Esophagus)Studies of the same condition, open and under way.
- More trials run by Dartmouth-Hitchcock Medical 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
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dartmouth-Hitchcock Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc., Ligand Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Konstantin H. Dragnev, MD, Principal investigator, Dartmouth-Hitchcock Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01116622
- Sponsor's protocol ID
- D0228
- Status last verified
- Nov 2014
- First submitted
- 14 Apr 2010
- Last updated
- 18 Oct 2023
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 18 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Clinical Study of Erlotinib (Tarceva) and Bexarotene (Targretin) Oral Capsules in Advanced Cancers of the Aerodigestive Tract
- ClinicalTrials.gov ID
- NCT01116622
- Acronym / sponsor ID
- D0228
- Keywords
- Aerodigestive, Targretin, Tarceva
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Dartmouth-Hitchcock Medical CenterUniversity, hospital or other
- Collaborators
- Genentech, Inc., Ligand Pharmaceuticals
- Study start
- Apr 2003
- Primary completion
- Apr 2014 (actual)
- Study completion
- Apr 2014 (actual)
- First posted
- 5 May 2010 (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.
Primary objective: To determine the Phase II doses and to evaluate the safety of administering bexarotene (Targretin®) daily in combination with oral erlotinib (Tarceva™) to patients with advanced aerodigestive tract cancers.
Secondary objectives: To evaluate the response rates, progression-free survival and overall survival of patients with advanced aerodigestive tract cancers treated with bexarotene (Targretin®) in combination with erlotinib (Tarceva™). To investigate the activity of this targeted combination therapy by evaluating changes in molecular markers from pre- and post-treatment buccal swab samples.
Detailed description
This is a single institution open label dose-ranging trial. Consecutive, eligible patients presenting with the diagnosis of advanced aerodigestive tract malignancy are to be enrolled in this study. All eligible patients will receive continuous daily oral erlotinib (Tarceva™) with daily bexarotene oral capsules (Targretin®). The two agents will be taken at the same time. Three dose levels of daily bexarotene in combination with daily erlotinib will be studied.
Eligible patients will be entered in cohorts of three at each dose level. Doses will not be escalated over the course of treatment of an individual patient. If a single patient experiences grade 4 hematologic or ≥ grade 3 non-hematologic toxicity (excluding hyperlipidemia and nausea/vomiting), the next group of three patients will be entered at the same dose. A maximum of 6 evaluable patients will be enrolled at any one dose level. Dose escalation is performed after all patients (3 or 6) at the previous dose level have received treatment for 4 weeks. Treatment will continue until progression of disease, unacceptable adverse effects, or patient refusal. If grade 4 hematologic or ≥ grade 3 non-hematologic toxicity (excluding hyperlipidemia and nausea/vomiting) is observed in two or more patients on dose level 1, the next three patients (or six if similar toxicity develops in one of the first three patients) will receive dose level -1. If such toxicity is seen in two or more patients, the trial will be terminated. We anticipate the maximum accrual of 18 patients to this trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Daily oral erlotinib and bexarotene capusles | Experimental | Drug: Bexarotene (Targretin®), Drug: Erlotinib (Tarceva™)Open label dose-ranging trial |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Pathological confirmation of advanced malignant aerodigestive tract tumo(lung, head and neck and esophagus)
- No known curative treatment.
- Age >18 years
- Karnofsky performance status ≥ 60%.
- Prior chemotherapy or radiotherapy is allowed.
Key exclusion criteria (15 listed)
- Organ dysfunction that precludes use of bexarotene or erlotinib:
- hepatic dysfunction, as evidenced by either:
- renal dysfunction, as evidenced by calculated creatinine clearance < 30 ml/min
- A serious uncontrolled medical disorder or active infection which would impair their ability to receive study treatment will be excluded.
- Significant cardiac disease, including uncontrolled high blood pressure, unstable angina, congestive heart failure, myocardial infarction within the previous 3 months or serious cardiac arrhythmias will be excluded. Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol will be excluded.
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 |
|---|---|---|
| Bexarotene (Targretin®)Also: Targetin, LGD1069Level -I 200 mg/m2 Level I 300 mg/m2 Level II 300 mg/m2 Level III 400 mg/m2 | Drug | Daily oral erlotinib and bexarotene capusles |
| Erlotinib (Tarceva™)Level -1 100mg Level I 100mg Level II 150mg Level III 150mg | Drug | Daily oral erlotinib and bexarotene capusles |
Primary outcome
Phase II dose determination and evaluation of the safety of administering bexarotene(Targretin®) daily in combination with oral erlotinib (Tarceva™) to patients with advanced aerodigestive tract cancers.
Time frame: When final patient is removed from study or at the discreation of the investigator
The purpose of this study is to evaluate the safety of daily oral administration of bexarotene in combination with erlotinib at three dose levels to patients with advanced aerodigestive tract cancer. At least 3 patients will be entered onto each dose level. Dose limiting toxicity is defined as grade 3 or greater non-hematologic toxicity or grade 4 hematologic toxicity. The recommended Phase II dose is defined as the highest dose level of bexarotene oral capsules in combination with oral erlotinib that induces DLT in fewer than 33% of patients.
2 secondary outcomes
Response rates, progression-free survival and overall survival of patients with advanced aerodigestive
Time frame: When final patient is removed from study or at the discretion of the investigator
Investigate the activity of this targeted combination therapy by evaluating changes in molecular markers from pre- and post-treatment buccal swab samples.
Time frame: When final patient is removed from study or at the discretion of the investigator
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 18 Oct 2023.
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.
Konstantin H. Dragnev, MD principal investigator
Dartmouth-Hitchcock Medical 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 Bexarotene (Targretin®) and Erlotinib (Tarceva™) in people with Advanced, Malignant Aerodigestive Tract Tumor (Lung, Head and Neck and Esophagus), run by Dartmouth-Hitchcock Medical 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 8 inclusion and 15 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 18 Oct 2023. 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?
Phase II dose determination and evaluation of the safety of administering bexarotene(Targretin®) daily in combination with oral erlotinib (Tarceva™) to patients with advanced aerodigestive tract cancers. (time frame: When final patient is removed from study or at the discreation of the investigator). 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 18 Oct 2023.