Head and Neck CancerPhase 1NCT00102635
4-HPR and FTI in Head and Neck Squamous Cell Carcinoma (HNSCC)
A Phase 1 study testing Fenretinide (4-HPR) and SCH66336 in people with Head and Neck Cancer, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
The primary objective of this study is to estimate the modulation of intermediate biological endpoints of the combination of 4-HPR and SCH66336, a farnesyl transferase inhibitor (FTI), across 4 randomly assigned dose levels in patients with locally advanced or recurrent head and neck cancer. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Head and Neck Cancer
- What is being tested?
- Fenretinide (4-HPR) and SCH66336
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Jan 2005to Nov 2006
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patient has histologically proven squamous cell carcinoma of the head and neck which is biopsy accessible and is not considered curable by standard measures.
- Patient has a Karnofsky performance status >/= 70%
- Patient has adequate bone marrow function: *WBC >/= 3,000 cells/mm^3, *ANC >/= 1,500 cells/mm^3, *platelet count >/= 100,000 cells/mm^3, *Hgb >/= 9.0 g/dL.
- Patient has adequate liver function: *total bilirubin level </= 2.0 mg/dL, *albumin >/= 2.5 g/dL.
- Transaminases (SGOT and/or SGPT) may be up to 2.5 x ULN if alkaline phosphatase is </= ULN, or alkaline phosphatase may be up to 4 x ULN if transaminases are </= ULN.
- Patient has adequate renal function: a serum creatinine < 2 mg/dl
- Patient has signed a written informed consent.
- Patient has received no more than 2 prior chemotherapeutic regimens for recurrent or metastatic disease. Prior biologic therapy is not included.
Who cannot join
- Patient has received 3 or more prior chemotherapeutic regimens for recurrent/metastatic disease.
- No biopsy accessible tissue.
- Patient has received radiation therapy within the past 6 months.
- Prior radiation to the biopsy site.
- Patient has signs or symptoms of acute infection requiring systemic therapy.
- Patient exhibits confusion, disorientation, or has a history of major psychiatric illness which may impair patient's understanding of the informed consent.
Show all 16Show fewer
- Patient has grade 3 or 4 neurotoxicity from previous anticancer treatment or significant neuropathy from any cause.
- Patient requires total parenteral nutrition with lipids.
- Surgery is anticipated to leave patient unable to swallow the SCH66336 or 4-HPR daily.
- Patient has a history of uncontrolled heart disease (including arrhythmia, angina, congestive heart failure, or any heart condition that cannot be controlled with regular ongoing medication)
- Because of the known teratogenic effect of retinoids, pregnant women and women who are currently breast-feeding may not participate in this study. All women of childbearing potential must have a negative pregnancy test within 24 hours prior to enrolling in the study.
- Serious infection or other intercurrent illness requiring immediate therapy.
- Inability to swallow oral medications, or other medical or social factors interfering with compliance.
- Patients may not take high dose synthetic or natural Vitamin A derivatives (>10,000 IU per day). Patients may not be taking high-dose vitamin A within 30 days of study entry.
- Patients should not take any anti-oxidants such as Vitamin E or Vitamin C
- Patients with pre-existing retinopathy
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase IB Randomized Translational Study of Fenretinide (4-HPR) in Combination With SCH66336, a Farnesyl Transferase Inhibitor, in Patients With Advanced or Recurrent Head and Neck Cancer
The primary objective of this study is to estimate the modulation of intermediate biological endpoints of the combination of 4-HPR and SCH66336, a farnesyl transferase inhibitor (FTI), across 4 randomly assigned dose levels in patients with locally advanced or recurrent head and neck cancer. We will also assess the activity, safety, tolerability and side effects of 4-HPR/SCH66336 and hope to establish a phase II regimen.
Read the detailed description
The drug fenretinide is a retinoid that is similar to vitamin A. It is believed that fenretinide can cause cancer cells to die. SCH66336 is a drug that blocks farnesyl protein transferase (a substance needed by cancer cells to grow). It is believed that SCH66336 may selectively stop cancer cells from growing while not affecting normal cells.
Both SCH66336 and fenretinide are taken orally and must be swallowed whole (i.e., the drugs may not be broken to make swallowing easier). Individuals who cannot take the study medications whole by mouth cannot enroll in this study.
In this study participants will receive SCH66336 twice a day for each day of a 21-day cycle. Participants will also take fenretinide twice a day on Days 1-7 of the same cycle. Before beginning treatment, participants will have a complete physical exam, including measurement of height, weight, and vital signs. Participants will have blood and urine tests, a chest x-ray, and an ECG (heart function test). Females who are able to become pregnant must have a negative blood pregnancy test. In addition, all participants will have a neurological exam and will complete a questionnaire about their night vision. Some individuals may need an eye exam.
Before beginning treatment, participants will have a biopsy of their tumor and will provide a sample of their buccal mucosa (inner cheek). In the biopsy, a sample of tumor tissue will be removed with a large needle. The buccal mucosa sample will be obtained by scraping the inside of the cheek. Participants will also have an extra blood sample (about 2 tablespoons) drawn. The tumor, buccal mucosa, and blood samples are all being obtained for research purposes only and will not directly benefit the participant.
During the study, a physician will examine participants at least once a week for the first cycle of treatment. A treatment cycle is 3 weeks. Participants will also have weekly blood tests. After the first cycle of treatment, participants will have exams every 3 weeks. In addition, participants will have urine tests every 3 weeks, a neurological exam after the first 3 weeks and then as needed, and a chest x-ray every 3 weeks. Every 3 months, participants will complete a questionnaire about their night vision and will have an eye exam, if needed.
While on this study, individuals will also participate in a pharmacokinetic study to measure the levels of the drugs in the blood. On the first day of treatment, the participant will have blood samples (about 1 teaspoon each) drawn before taking fenretinide and then 1, 2, 4, 6, 9, and 12 hours after taking fenretinide. The participant will not take the first dose of SCH66336 until after these blood samples have been taken. Additional blood samples (about 1 teaspoon each) will be taken at these same times on Day 7 of the first treatment cycle and on Day 1 of the second treatment cycle. A single blood sample (about 1 teaspoon) will be taken before taking the study drugs on Day 7 of treatment Cycles 3, 4, 5, and 6.
Participants will have biopsies of their tumors, extra blood tests and will provide buccal mucosa samples on Days 7 and 21 of the first treatment cycle. These biopsies, cheek scrapings, and extra blood tests are for research purposes only and will not directly benefit the participant. Approximately two tablespoons of blood will be drawn during each of these extra blood tests. This blood, buccal mucosa (cheek), and tumor tissue will be studied to learn how the treatment drugs work in the body and what effects they have. Participants may remain on the study as long as they are responding to the SCH66336/fenretinide combination and as long as their physician feels it is of benefit.
After completing treatment, participants will be contacted about every 3 months to check on the disease status. Participants will come to M.D. Anderson for clinical evaluations every 3 months for a period of 24 months.
Fenretinide is in the form of capsules and SCH66336 is in the form of tablets. Participants will take the fenretinide capsules by mouth twice a day for seven days in a row at the start of each treatment cycle. Participants will take the SCH66336 tablets twice a day for 21 days in a row in each cycle. Participants will be given a "pill diary" in which they should record when they take the study medications and how many capsules and tablets they take. Participants will bring this diary and any unused medication when they return to the clinic for their check-ups. At the beginning of a treatment cycle, participants should take both drugs together at least 8 hours apart with either a high-fat meal or a glass of whole milk. Participants should continue taking the SCH66336 tablets at least 8 hours apart and with a meal or a glass of whole milk during Days 8-21 of each treatment cycle. Participants will not take fenretinide capsules during Days 8-21 of a treatment cycle.
While on this study, participants may not drink grapefruit juice.
This is an investigational study. The FDA has authorized the use of this drug combination in research but has not approved it for widespread use. About 40 individuals will take part in this study. All will be enrolled at M.D. Anderson Cancer Center.
- Conditions
- Head and Neck Cancer
- Being tested
- Fenretinide (4-HPR), SCH66336
- Keywords
- apoptotic activity, 4-HPR, FTI, Fenretinide, SCH66336, Farnesyl Transferase Inhibitor, HNC
- Medical subject headings
- Head and Neck Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fenretinide (4-HPR)Drug
Oral 100 mg capsules in two divided doses at least 8 hours apart for 7 days each cycle.
SCH66336Drug
Also called Lonafarnib, SCH 66336, Sarasar
Oral capsules with 50 mg, 75 mg, or 100 mg formulation in two divided doses at least 8 hours apart for 21 days each cycle.
| Study group | Role | What they receive |
|---|---|---|
| 4-HPR + FTI | Experimental | SCH66336 daily for 21 days each cycle and with 4-HPR daily on days 1-7 only. On day 1 of cycle 1, 4-HPR only beginning SCH66336 on day 2 of cycle 1. Receives: Drug: Fenretinide (4-HPR); Drug: SCH66336 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD)
MTD derived from lack of dose limiting toxicities (DLT) in 4 differing dose levels.
Measured: 21 day courses
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2005 (estimated)
- Study start20 Jan 2005
- Primary completionJan 2006
- Study completionNov 2006
Why it stopped: Slow accrual.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Head and Neck CancerStudies of the same condition, open and under way.
- More trials run by M.D. Anderson 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), Schering-Plough
- Responsible party
- Sponsor
- Investigators
- Edward S Kim, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00102635
- Sponsor's protocol ID
- ID01-455
- Status last verified
- Nov 2018
- First submitted
- 31 Jan 2005
- Last updated
- 15 Nov 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IB Randomized Translational Study of Fenretinide (4-HPR) in Combination With SCH66336, a Farnesyl Transferase Inhibitor, in Patients With Advanced or Recurrent Head and Neck Cancer
- ClinicalTrials.gov ID
- NCT00102635
- Acronym / sponsor ID
- ID01-455
- Conditions
- Head and Neck Cancer
- Keywords
- apoptotic activity, 4-HPR, FTI, Fenretinide, SCH66336, Farnesyl Transferase Inhibitor, HNC
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow accrual.
- Enrolment
- 1 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), Schering-Plough
- Study start
- 20 Jan 2005 (actual)
- Primary completion
- Jan 2006 (actual)
- Study completion
- Nov 2006 (actual)
- First posted
- 1 Feb 2005 (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 primary objective of this study is to estimate the modulation of intermediate biological endpoints of the combination of 4-HPR and SCH66336, a farnesyl transferase inhibitor (FTI), across 4 randomly assigned dose levels in patients with locally advanced or recurrent head and neck cancer. We will also assess the activity, safety, tolerability and side effects of 4-HPR/SCH66336 and hope to establish a phase II regimen.
Detailed description
The drug fenretinide is a retinoid that is similar to vitamin A. It is believed that fenretinide can cause cancer cells to die. SCH66336 is a drug that blocks farnesyl protein transferase (a substance needed by cancer cells to grow). It is believed that SCH66336 may selectively stop cancer cells from growing while not affecting normal cells.
Both SCH66336 and fenretinide are taken orally and must be swallowed whole (i.e., the drugs may not be broken to make swallowing easier). Individuals who cannot take the study medications whole by mouth cannot enroll in this study.
In this study participants will receive SCH66336 twice a day for each day of a 21-day cycle. Participants will also take fenretinide twice a day on Days 1-7 of the same cycle. Before beginning treatment, participants will have a complete physical exam, including measurement of height, weight, and vital signs. Participants will have blood and urine tests, a chest x-ray, and an ECG (heart function test). Females who are able to become pregnant must have a negative blood pregnancy test. In addition, all participants will have a neurological exam and will complete a questionnaire about their night vision. Some individuals may need an eye exam.
Before beginning treatment, participants will have a biopsy of their tumor and will provide a sample of their buccal mucosa (inner cheek). In the biopsy, a sample of tumor tissue will be removed with a large needle. The buccal mucosa sample will be obtained by scraping the inside of the cheek. Participants will also have an extra blood sample (about 2 tablespoons) drawn. The tumor, buccal mucosa, and blood samples are all being obtained for research purposes only and will not directly benefit the participant.
During the study, a physician will examine participants at least once a week for the first cycle of treatment. A treatment cycle is 3 weeks. Participants will also have weekly blood tests. After the first cycle of treatment, participants will have exams every 3 weeks. In addition, participants will have urine tests every 3 weeks, a neurological exam after the first 3 weeks and then as needed, and a chest x-ray every 3 weeks. Every 3 months, participants will complete a questionnaire about their night vision and will have an eye exam, if needed.
While on this study, individuals will also participate in a pharmacokinetic study to measure the levels of the drugs in the blood. On the first day of treatment, the participant will have blood samples (about 1 teaspoon each) drawn before taking fenretinide and then 1, 2, 4, 6, 9, and 12 hours after taking fenretinide. The participant will not take the first dose of SCH66336 until after these blood samples have been taken. Additional blood samples (about 1 teaspoon each) will be taken at these same times on Day 7 of the first treatment cycle and on Day 1 of the second treatment cycle. A single blood sample (about 1 teaspoon) will be taken before taking the study drugs on Day 7 of treatment Cycles 3, 4, 5, and 6.
Participants will have biopsies of their tumors, extra blood tests and will provide buccal mucosa samples on Days 7 and 21 of the first treatment cycle. These biopsies, cheek scrapings, and extra blood tests are for research purposes only and will not directly benefit the participant. Approximately two tablespoons of blood will be drawn during each of these extra blood tests. This blood, buccal mucosa (cheek), and tumor tissue will be studied to learn how the treatment drugs work in the body and what effects they have. Participants may remain on the study as long as they are responding to the SCH66336/fenretinide combination and as long as their physician feels it is of benefit.
After completing treatment, participants will be contacted about every 3 months to check on the disease status. Participants will come to M.D. Anderson for clinical evaluations every 3 months for a period of 24 months.
Fenretinide is in the form of capsules and SCH66336 is in the form of tablets. Participants will take the fenretinide capsules by mouth twice a day for seven days in a row at the start of each treatment cycle. Participants will take the SCH66336 tablets twice a day for 21 days in a row in each cycle. Participants will be given a "pill diary" in which they should record when they take the study medications and how many capsules and tablets they take. Participants will bring this diary and any unused medication when they return to the clinic for their check-ups. At the beginning of a treatment cycle, participants should take both drugs together at least 8 hours apart with either a high-fat meal or a glass of whole milk. Participants should continue taking the SCH66336 tablets at least 8 hours apart and with a meal or a glass of whole milk during Days 8-21 of each treatment cycle. Participants will not take fenretinide capsules during Days 8-21 of a treatment cycle.
While on this study, participants may not drink grapefruit juice.
This is an investigational study. The FDA has authorized the use of this drug combination in research but has not approved it for widespread use. About 40 individuals will take part in this study. All will be enrolled at M.D. Anderson Cancer Center.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 4-HPR + FTI | Experimental | Drug: Fenretinide (4-HPR), Drug: SCH66336SCH66336 daily for 21 days each cycle and with 4-HPR daily on days 1-7 only. On day 1 of cycle 1, 4-HPR only beginning SCH66336 on day 2 of cycle 1. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- Patient has histologically proven squamous cell carcinoma of the head and neck which is biopsy accessible and is not considered curable by standard measures.
- Patient has a Karnofsky performance status >/= 70%
- Patient has adequate bone marrow function: *WBC >/= 3,000 cells/mm^3, *ANC >/= 1,500 cells/mm^3, *platelet count >/= 100,000 cells/mm^3, *Hgb >/= 9.0 g/dL.
- Patient has adequate liver function: *total bilirubin level </= 2.0 mg/dL, *albumin >/= 2.5 g/dL.
- Transaminases (SGOT and/or SGPT) may be up to 2.5 x ULN if alkaline phosphatase is </= ULN, or alkaline phosphatase may be up to 4 x ULN if transaminases are </= ULN.
Key exclusion criteria (16 listed)
- Patient has received 3 or more prior chemotherapeutic regimens for recurrent/metastatic disease.
- No biopsy accessible tissue.
- Patient has received radiation therapy within the past 6 months.
- Prior radiation to the biopsy site.
- Patient has signs or symptoms of acute infection requiring systemic 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 |
|---|---|---|
| Fenretinide (4-HPR)Oral 100 mg capsules in two divided doses at least 8 hours apart for 7 days each cycle. | Drug | 4-HPR + FTI |
| SCH66336Also: Lonafarnib, SCH 66336, SarasarOral capsules with 50 mg, 75 mg, or 100 mg formulation in two divided doses at least 8 hours apart for 21 days each cycle. | Drug | 4-HPR + FTI |
Primary outcome
Maximum Tolerated Dose (MTD)
Time frame: 21 day courses
MTD derived from lack of dose limiting toxicities (DLT) in 4 differing dose levels.
Results and safety
The study was stopped early (reason given: Slow accrual.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Nov 2018.
- UT MD Anderson Cancer Center websiteLink provided by the sponsor.
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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.
Edward S Kim, MD principal investigator
M.D. Anderson 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 Fenretinide (4-HPR) and SCH66336 in people with Head and Neck Cancer, run by M.D. Anderson 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 8 inclusion and 16 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 15 Nov 2018. 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: Slow accrual.). 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 (MTD) (time frame: 21 day courses). 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 15 Nov 2018.