Adult Anaplastic AstrocytomaPhase 1NCT01103375
Erlotinib Hydrochloride and Isotretinoin in Treating Patients With Recurrent Malignant Glioma
A Phase 1 study testing erlotinib hydrochloride, isotretinoin and laboratory biomarker analysis in people with Adult Anaplastic Astrocytoma and Adult Anaplastic Oligodendroglioma, run by Wake Forest University Health Sciences at 1 site in United States.
Trial summary
This phase I trial is studying the side effects and best dose of erlotinib hydrochloride when given with isotretinoin in treating patients with recurrent malignant glioma. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adult Anaplastic Astrocytoma, Adult Anaplastic Oligodendroglioma, Adult Diffuse Astrocytoma
- What is being tested?
- erlotinib hydrochloride, isotretinoin and laboratory biomarker analysis
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- May 2010to Mar 2013
- 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
- Histologically proven malignant glioma (glioblastoma multiforme, anaplastic astrocytoma, anaplastic oligodendroglioma, or anaplastic mixed oligoastrocytoma) which is progressive or recurrent after radiation therapy +/- chemotherapy; patients with previous low grade glioma who progressed after radiotherapy +/- chemotherapy and are biopsied and found to have a high grade glioma are eligible Karnofsky performance status of >= 60% Patients - both males and females - with reproductive potential (i.e., premenopausal or menopausal for less than 1 year and not surgically sterilized) must practice at least 2 contraceptive measures throughout the study Patients must be registered and meet all the requirements of iPLEDGE in order to receive 13-cis-Retinoic Acid (CRA) Patients must provide verbal and written informed consent to participate in the study Patients must have a Mini Mental Status Exam score >= 15 Patients must have a 12-lead electrocardiogram (EKG) without evidence of any clinically significant abnormalities Absolute neutrophil count (ANC) >= 1,500/mm^3 Platelets >= 100,000/mm^3 Aspartate aminotransferase (AST) =< 2.5 upper limit of normal (ULN) (ULN = 50 U/L) Alanine aminotransferase (ALT) =< 2.5 ULN (ULN = 50 U/L) Total Bilirubin =< 1.5 mg/dL Alkaline phosphatase (Alk. Phos) =< 5X ULN (ULN = 125 U/dL) Estimated (Estim.) creatinine (Cr) Clearance > 50 ml/min Fasting total cholesterol < 300 mg/dL Fasting triglycerides < 250 mg/dL Two separate, laboratory pregnancy tests within 14 days of registration (for women of childbearing potential) Patients must have recovered from the toxicity of prior therapy; specifically, there must be at least a 3 month interval from the completion of the most recent course of radiation therapy, at least a 3 month interval from the implantation of Gliadel wafer(s), at least a 3 week interval from the completion of a non-nitrosourea-containing chemotherapy regimen, and at least a 6 week interval from the completion of a nitrosourea-containing chemo-regimen
Who cannot join
- Pregnant or breast-feeding women Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, severe cardiovascular disease including recent (< 6 months) myocardial infarction, severe psychiatric illness that would limit compliance with study requirements, or any other disorder that would be incompatible with the study therapy Any history of inflammatory bowel disease Any history of uncontrolled depression, any history of hospitalization for depression, or any history of suicidal thoughts or attempt(s) Patients receiving concurrent therapy for their tumor (with the exception of steroids) Must have at least a 10 day interval from last dose of vitamin A, tetracyclines, micro-dosed progesterone preparations, norethindrone/ethinyl estradiol, St. John's Wort, fish oil supplements, or phenytoin or other P450 enzyme inducing antiepileptic drugs Current smokers (Smoking >= 11 cigarettes per day), as smoking increases metabolism and decreases serum levels of erlotinib Participants may not have received prior EGFR inhibitors for any disease Patients with a history of allergic reactions to 13-cis-retinoic acid (CRA) or compounds of similar biologic or chemical composition to CRA Known allergy to proton pump inhibitors
Trial locations and contacts
1 site in 1 country.
United States1 site
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
About this study
Official title: A Phase I Single Arm Open Label Study of Erlotinib and 13-cis-Retinoic Acid (CRA) in Patients With Recurrent Malignant Gliomas
This phase I trial is studying the side effects and best dose of erlotinib hydrochloride when given with isotretinoin in treating patients with recurrent malignant glioma. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Isotretinoin may help cells that are involved in the body's immune response to work better. Giving erlotinib hydrochloride together with isotretinoin may kill more tumor cells
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the recommended phase II doses of erlotinib (erlotinib hydrochloride) and 13-cis-retinoic acid (CRA) when administered to adults with recurrent malignant glioma who are not receiving cytochrome P450 enzyme-inducing antiepileptic drugs (EIAEDs).
SECONDARY OBJECTIVES:
- To assess dose-related toxicities. II. To measure 6 month progression-free survival and overall survival. III. To estimate response rates in those patients with measurable disease. IV. To evaluate for epidermal growth factor receptor (EGFR)vIII, phosphatase and tensin homolog (PTEN), cyclin D1, cyclin E, and RARbeta1 expression in tumor samples from enrolled patients as predictors of clinical benefit from this combination.
OUTLINE: This is a dose-escalation study.
Patients receive isotretinoin orally (PO) once daily (QD) on days 1-21 and erlotinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed for up to 2 years.
- Conditions
- Adult Anaplastic Astrocytoma, Adult Anaplastic Oligodendroglioma, Adult Diffuse Astrocytoma, Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma
- Being tested
- erlotinib hydrochloride, isotretinoin, laboratory biomarker analysis, protein expression analysis
- Medical subject headings
- Astrocytoma, Oligodendroglioma, Glioblastoma, Gliosarcoma, Glioma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
erlotinib hydrochlorideDrug
Also called CP-358,774, erlotinib, OSI-774
Given PO
isotretinoinDrug
Also called 13-CRA, Amnesteem, Cistane, Claravis
Given PO
laboratory biomarker analysisOther
Correlative study
protein expression analysisGenetic
Correlative study
| Study group | Role | What they receive |
|---|---|---|
| Treatment (enzyme inhibitor, immunotherapy) | Experimental | Patients receive isotretinoin PO QD on days 1-21 and erlotinib hydrochloride PO QD on days 1-28. Receives: Drug: erlotinib hydrochloride; Drug: isotretinoin; Other: laboratory biomarker analysis; Genetic: protein expression analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recommended phase II doses of erlotinib hydrochloride and isotretinoin
At least 3 patients will be treated at each dose level and the maximum tolerated dose (MTD) will be determined. Patients will be evaluated for dose-limiting toxicity (DLT) in the first 3 weeks on protocol.
Measured: 3 weeks
Secondary outcomes (5)
Toxicity as assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0
Measured: Up to 2 years
Progression-free survival
Measured: At 6 months
Overall survival
Measured: At 6 months
Response rates (complete or partial response)
Measured: Up to 2 years
EGFRvIII, PTEN, cyclin D1, cyclin E, and RARbeta1 expression in tumor samples
Measured: Pre-study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Apr 2010 (estimated)
- Study startMay 2010
- Primary completionJan 2013
- Study completionMar 2013
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 Adult Anaplastic AstrocytomaStudies of the same condition, open and under way.
- More trials run by Wake Forest University Health SciencesThe 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
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Glenn Lesser, Principal investigator, Wake Forest University Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01103375
- Sponsor's protocol ID
- IRB00012306
- Other IDs
- NCI-2010-00132, CCCWFU 91209
- Status last verified
- Jul 2018
- First submitted
- 13 Apr 2010
- Last updated
- 1 Aug 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Single Arm Open Label Study of Erlotinib and 13-cis-Retinoic Acid (CRA) in Patients With Recurrent Malignant Gliomas
- ClinicalTrials.gov ID
- NCT01103375
- Acronym / sponsor ID
- IRB00012306
- Conditions
- Adult Anaplastic Astrocytoma, Adult Anaplastic Oligodendroglioma, Adult Diffuse Astrocytoma, Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow accrual
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- May 2010
- Primary completion
- Jan 2013 (actual)
- Study completion
- Mar 2013 (actual)
- First posted
- 14 Apr 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.
This phase I trial is studying the side effects and best dose of erlotinib hydrochloride when given with isotretinoin in treating patients with recurrent malignant glioma. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Isotretinoin may help cells that are involved in the body's immune response to work better. Giving erlotinib hydrochloride together with isotretinoin may kill more tumor cells
Detailed description
PRIMARY OBJECTIVES:
- To determine the recommended phase II doses of erlotinib (erlotinib hydrochloride) and 13-cis-retinoic acid (CRA) when administered to adults with recurrent malignant glioma who are not receiving cytochrome P450 enzyme-inducing antiepileptic drugs (EIAEDs).
SECONDARY OBJECTIVES:
- To assess dose-related toxicities. II. To measure 6 month progression-free survival and overall survival. III. To estimate response rates in those patients with measurable disease. IV. To evaluate for epidermal growth factor receptor (EGFR)vIII, phosphatase and tensin homolog (PTEN), cyclin D1, cyclin E, and RARbeta1 expression in tumor samples from enrolled patients as predictors of clinical benefit from this combination.
OUTLINE: This is a dose-escalation study.
Patients receive isotretinoin orally (PO) once daily (QD) on days 1-21 and erlotinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed for up to 2 years.
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, immunotherapy) | Experimental | Drug: erlotinib hydrochloride, Drug: isotretinoin, Other: laboratory biomarker analysis, Genetic: protein expression analysisPatients receive isotretinoin PO QD on days 1-21 and erlotinib hydrochloride PO QD on days 1-28. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Histologically proven malignant glioma (glioblastoma multiforme, anaplastic astrocytoma, anaplastic oligodendroglioma, or anaplastic mixed oligoastrocytoma) which is progressive or recurrent after radiation therapy +/- chemotherapy; patients with previous low grade glioma who progressed after radiotherapy +/- chemotherapy and are biopsied and found to have a high grade glioma are eligible Karnofsky performance status of >= 60% Patients - both males and females - with reproductive potential (i.e., premenopausal or menopausal for less than 1 year and not surgically sterilized) must practice at least 2 contraceptive measures throughout the study Patients must be registered and meet all the requirements of iPLEDGE in order to receive 13-cis-Retinoic Acid (CRA) Patients must provide verbal and written informed consent to participate in the study Patients must have a Mini Mental Status Exam score >= 15 Patients must have a 12-lead electrocardiogram (EKG) without evidence of any clinically significant abnormalities Absolute neutrophil count (ANC) >= 1,500/mm^3 Platelets >= 100,000/mm^3 Aspartate aminotransferase (AST) =< 2.5 upper limit of normal (ULN) (ULN = 50 U/L) Alanine aminotransferase (ALT) =< 2.5 ULN (ULN = 50 U/L) Total Bilirubin =< 1.5 mg/dL Alkaline phosphatase (Alk. Phos) =< 5X ULN (ULN = 125 U/dL) Estimated (Estim.) creatinine (Cr) Clearance > 50 ml/min Fasting total cholesterol < 300 mg/dL Fasting triglycerides < 250 mg/dL Two separate, laboratory pregnancy tests within 14 days of registration (for women of childbearing potential) Patients must have recovered from the toxicity of prior therapy; specifically, there must be at least a 3 month interval from the completion of the most recent course of radiation therapy, at least a 3 month interval from the implantation of Gliadel wafer(s), at least a 3 week interval from the completion of a non-nitrosourea-containing chemotherapy regimen, and at least a 6 week interval from the completion of a nitrosourea-containing chemo-regimen
Key exclusion criteria (1 listed)
- Pregnant or breast-feeding women Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, severe cardiovascular disease including recent (< 6 months) myocardial infarction, severe psychiatric illness that would limit compliance with study requirements, or any other disorder that would be incompatible with the study therapy Any history of inflammatory bowel disease Any history of uncontrolled depression, any history of hospitalization for depression, or any history of suicidal thoughts or attempt(s) Patients receiving concurrent therapy for their tumor (with the exception of steroids) Must have at least a 10 day interval from last dose of vitamin A, tetracyclines, micro-dosed progesterone preparations, norethindrone/ethinyl estradiol, St. John's Wort, fish oil supplements, or phenytoin or other P450 enzyme inducing antiepileptic drugs Current smokers (Smoking >= 11 cigarettes per day), as smoking increases metabolism and decreases serum levels of erlotinib Participants may not have received prior EGFR inhibitors for any disease Patients with a history of allergic reactions to 13-cis-retinoic acid (CRA) or compounds of similar biologic or chemical composition to CRA Known allergy to proton pump inhibitors
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 |
|---|---|---|
| erlotinib hydrochlorideAlso: CP-358,774, erlotinib, OSI-774Given PO | Drug | Treatment (enzyme inhibitor, immunotherapy) |
| isotretinoinAlso: 13-CRA, Amnesteem, Cistane, ClaravisGiven PO | Drug | Treatment (enzyme inhibitor, immunotherapy) |
| laboratory biomarker analysisCorrelative study | Other | Treatment (enzyme inhibitor, immunotherapy) |
| protein expression analysisCorrelative study | Genetic | Treatment (enzyme inhibitor, immunotherapy) |
Primary outcome
Recommended phase II doses of erlotinib hydrochloride and isotretinoin
Time frame: 3 weeks
At least 3 patients will be treated at each dose level and the maximum tolerated dose (MTD) will be determined. Patients will be evaluated for dose-limiting toxicity (DLT) in the first 3 weeks on protocol.
5 secondary outcomes
Toxicity as assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0
Time frame: Up to 2 years
Progression-free survival
Time frame: At 6 months
Overall survival
Time frame: At 6 months
Response rates (complete or partial response)
Time frame: Up to 2 years
EGFRvIII, PTEN, cyclin D1, cyclin E, and RARbeta1 expression in tumor samples
Time frame: Pre-study
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 1 Aug 2018.
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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.
Glenn Lesser principal investigator
Wake Forest University Health Sciences
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 erlotinib hydrochloride, isotretinoin and laboratory biomarker analysis in people with Adult Anaplastic Astrocytoma and Adult Anaplastic Oligodendroglioma, run by Wake Forest University Health Sciences 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 1 inclusion and 1 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 1 Aug 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?
Recommended phase II doses of erlotinib hydrochloride and isotretinoin (time frame: 3 weeks). 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 1 Aug 2018; AzTrials last refreshed its copy on 8 Nov 2026.