Adult Solid NeoplasmPhase 1NCT00334789
Belinostat and Isotretinoin in Treating Patients With Solid Tumors That Are Metastatic or That Cannot Be Removed by Surgery
A Phase 1 study testing Belinostat, Isotretinoin and Pharmacological Study in people with Adult Solid Neoplasm, run by National Cancer Institute (NCI) at 5 sites in United States.
Trial summary
This phase I trial is studying the side effects and best dose of belinostat when given together with isotretinoin in treating patients with metastatic or unresectable solid tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adult Solid Neoplasm
- What is being tested?
- Belinostat, Isotretinoin and Pharmacological Study
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 51 participants
- Where
- 5 sitesUnited States
- Study dates
- 12 Jun 2006to 29 Mar 2018
- 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 or cytologically confirmed metastatic or unresectable solid tumor for which standard curative or palliative measures do not exist or are no longer effective
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 50%)
- Life expectancy of greater than 3 months
- Leukocytes >= 3,000/mcL
- Absolute neutrophil count >= 1,500/mcL
- Platelets >= 100,000/mcL
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- Total bilirubin within normal institutional limits
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
- Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min for patients with creatinine levels above institutional normal
- Eligibility of patients receiving any medications or substances known to affect or with the potential to affect the activity or pharmacokinetics of belinostat will be determined following review of their case by the Principal Investigator
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- Ability to understand and the willingness to sign a written informed consent document
Who cannot join
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- Patients may not be receiving any other investigational agents
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to belinostat or other agents used in study
- Patients should not have taken valproic acid, another histone deacetylase inhibitor, for at least 2 weeks prior to enrollment
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements
- A marked baseline prolongation of QT/QTc interval, e.g., repeated demonstration of a QTc interval > 500 msec; Long QT Syndrome; the required use of concomitant medication on belinostat infusion days that may cause Torsade de Pointes
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- Significant cardiovascular disease including unstable angina pectoris, uncontrolled hypertension, congestive heart failure related to primary cardiac disease, a condition requiring anti-arrhythmic therapy, ischemic or severe valvular heart disease, or a myocardial infarction within 6 months prior to the trial entry
- Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with belinostat
- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
City of Hope Comprehensive Cancer Center
Duarte, California, 91010
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
City of Hope South Pasadena
South Pasadena, California, 91030
About this study
Official title: A Phase 1 Trial of PXD101 in Combination With 13-cis-Retinoic Acid in Advanced Solid Tumor Malignancies
This phase I trial is studying the side effects and best dose of belinostat when given together with isotretinoin in treating patients with metastatic or unresectable solid tumors. Belinostat may stop the growth of tumor cells by blocking blood flow to the tumor and by blocking some of the enzymes needed for cell growth. Isotretinoin may cause solid tumor cells to look more like normal cells, and to grow and spread more slowly. Giving belinostat together with isotretinoin may be an effective treatment for metastatic or unresectable solid tumors.
Read the detailed description
PRIMARY OBJECTIVES:
- To assess the safety and feasibility of combining PXD101 (belinostat) with 13-cis-retinoic acid [13-cRA] (isotretinoin) in patients with advanced solid tumor malignancies.
II. To define the maximum tolerated dose (MTD) of PXD101 when administered in combination with 13-cRA and to describe the toxicities at each dose studied.
III. To evaluate the pharmacokinetics of PXD101 and 13-cRA when given in combination.
SECONDARY OBJECTIVES:
- To demonstrate upregulation of retinoic acid receptor-beta (RARβ) and retinoic X-receptor (RXR) expression in tumor tissues after treatment with PXD101 and 13-cRA.
II. To measure apoptosis in tumor biopsies after treatment. III. To assess the change in gene expression after exposure to PXD101 and 13-cRA.
IV. To document any clinical activity of the combination of PXD101 and 13-cRA.
OUTLINE: This is a multicenter, dose-escalation study of belinostat.
Patients receive belinostat intravenously (IV) over 30 minutes on days 1-5 and isotretinoin orally (PO) once daily (QD) on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of PXD101 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity during the first course of therapy.
Once the MTD is determined, an expanded cohort of 10 patients are enrolled and treated at the MTD. These patients also undergo blood collection periodically during treatment for pharmacokinetic studies.
All patients undergo blood collection, buccal scrapings, and tumor biopsies periodically for biomarker, pharmacodynamic, gene expression, and laboratory studies.
After completion of study treatment, patients are followed for >= 8 weeks.
- Conditions
- Adult Solid Neoplasm
- Being tested
- Belinostat, Isotretinoin, Pharmacological Study
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BelinostatDrug
Also called Beleodaq, PXD 101, PXD101
Given IV
IsotretinoinDrug
Also called 13-cis retinoic acid, 13-cis-Retinoate, 13-cis-Retinoic Acid, 13-cis-Vitamin A Acid
Given orally
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (belinostat, isotretinoin) | Experimental | Patients receive belinostat IV over 30 minutes on days 1-5 and isotretinoin PO QD on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of belinostat until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity during the first course of therapy.
Once the MTD is determined, an expanded cohort of 10 patients are enrolled and treated at the MTD. These patients also undergo blood collection periodically during treatment for pharmacokinetic studies.
All patients undergo blood collection, buccal scrapings, and tumor biopsies periodically for biomarker, pharmacodynamic, gene expression, and laboratory studies. Receives: Drug: Belinostat; Drug: Isotretinoin; Other: Pharmacological Study |
What is being measured
The primary outcome is the main question the study is designed to answer.
MTD of belinostat in combination with isotretinoin determined by dose limiting toxicities graded according to NCI CTCAE 4.0
Tables will be created to summarize these toxicities and side effects by dose and by cycle. Tabular and graphical summaries will be used to explore the relationship of type and grade of toxicity to dose, cycle, and pharmacokinetics.
Measured: 21 days
Secondary outcomes (3)
Response evaluated using Response Evaluation Criteria in Solid Tumors (RECIST)
Measured: Up to 8 weeks
Survival
Measured: Up to 8 weeks
Time to failure
Measured: Up to 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jun 2006 (estimated)
- Study start12 Jun 2006
- Primary completion29 Mar 2018
- Study completion29 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Adult Solid NeoplasmStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Thehang Luu, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00334789
- Sponsor's protocol ID
- NCI-2009-00142
- Other IDs
- NCI-2009-00142, PHI-53, CDR0000479715, PHI-53, 7251, P30CA033572, U01CA062505, U01CA099168
- Status last verified
- Oct 2017
- First submitted
- 7 Jun 2006
- Last updated
- 3 Apr 2018
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Trial of PXD101 in Combination With 13-cis-Retinoic Acid in Advanced Solid Tumor Malignancies
- ClinicalTrials.gov ID
- NCT00334789
- Acronym / sponsor ID
- NCI-2009-00142
- Conditions
- Adult Solid Neoplasm
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 51 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 12 Jun 2006 (actual)
- Primary completion
- 29 Mar 2018 (actual)
- Study completion
- 29 Mar 2018 (actual)
- First posted
- 8 Jun 2006 (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 belinostat when given together with isotretinoin in treating patients with metastatic or unresectable solid tumors. Belinostat may stop the growth of tumor cells by blocking blood flow to the tumor and by blocking some of the enzymes needed for cell growth. Isotretinoin may cause solid tumor cells to look more like normal cells, and to grow and spread more slowly. Giving belinostat together with isotretinoin may be an effective treatment for metastatic or unresectable solid tumors.
Detailed description
PRIMARY OBJECTIVES:
- To assess the safety and feasibility of combining PXD101 (belinostat) with 13-cis-retinoic acid [13-cRA] (isotretinoin) in patients with advanced solid tumor malignancies.
II. To define the maximum tolerated dose (MTD) of PXD101 when administered in combination with 13-cRA and to describe the toxicities at each dose studied.
III. To evaluate the pharmacokinetics of PXD101 and 13-cRA when given in combination.
SECONDARY OBJECTIVES:
- To demonstrate upregulation of retinoic acid receptor-beta (RARβ) and retinoic X-receptor (RXR) expression in tumor tissues after treatment with PXD101 and 13-cRA.
II. To measure apoptosis in tumor biopsies after treatment. III. To assess the change in gene expression after exposure to PXD101 and 13-cRA.
IV. To document any clinical activity of the combination of PXD101 and 13-cRA.
OUTLINE: This is a multicenter, dose-escalation study of belinostat.
Patients receive belinostat intravenously (IV) over 30 minutes on days 1-5 and isotretinoin orally (PO) once daily (QD) on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of PXD101 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity during the first course of therapy.
Once the MTD is determined, an expanded cohort of 10 patients are enrolled and treated at the MTD. These patients also undergo blood collection periodically during treatment for pharmacokinetic studies.
All patients undergo blood collection, buccal scrapings, and tumor biopsies periodically for biomarker, pharmacodynamic, gene expression, and laboratory studies.
After completion of study treatment, patients are followed for >= 8 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (belinostat, isotretinoin) | Experimental | Drug: Belinostat, Drug: Isotretinoin, Other: Pharmacological StudyPatients receive belinostat IV over 30 minutes on days 1-5 and isotretinoin PO QD on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of belinostat until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity during the first course of therapy. Once the MTD is determined, an expanded cohort of 10 patients are enrolled and treated at the MTD. These patients also undergo blood collection periodically during treatment for pharmacokinetic studies. All patients undergo blood collection, buccal scrapings, and tumor biopsies periodically for biomarker, pharmacodynamic, gene expression, and laboratory studies. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Patients must have histologically or cytologically confirmed metastatic or unresectable solid tumor for which standard curative or palliative measures do not exist or are no longer effective
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 50%)
- Life expectancy of greater than 3 months
- Leukocytes >= 3,000/mcL
- Absolute neutrophil count >= 1,500/mcL
Key exclusion criteria (9 listed)
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- Patients may not be receiving any other investigational agents
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to belinostat or other agents used in study
- Patients should not have taken valproic acid, another histone deacetylase inhibitor, for at least 2 weeks prior to enrollment
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements
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 |
|---|---|---|
| BelinostatAlso: Beleodaq, PXD 101, PXD101Given IV | Drug | Treatment (belinostat, isotretinoin) |
| IsotretinoinAlso: 13-cis retinoic acid, 13-cis-Retinoate, 13-cis-Retinoic Acid, 13-cis-Vitamin A AcidGiven orally | Drug | Treatment (belinostat, isotretinoin) |
| Pharmacological StudyCorrelative studies | Other | Treatment (belinostat, isotretinoin) |
Primary outcome
MTD of belinostat in combination with isotretinoin determined by dose limiting toxicities graded according to NCI CTCAE 4.0
Time frame: 21 days
Tables will be created to summarize these toxicities and side effects by dose and by cycle. Tabular and graphical summaries will be used to explore the relationship of type and grade of toxicity to dose, cycle, and pharmacokinetics.
3 secondary outcomes
Response evaluated using Response Evaluation Criteria in Solid Tumors (RECIST)
Time frame: Up to 8 weeks
Survival
Time frame: Up to 8 weeks
Time to failure
Time frame: Up to 8 weeks
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 3 Apr 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.
Thehang Luu principal investigator
City of Hope Medical Center
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Belinostat, Isotretinoin and Pharmacological Study in people with Adult Solid Neoplasm, run by National Cancer Institute (NCI) at 5 sites 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 12 inclusion and 9 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 3 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites 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?
MTD of belinostat in combination with isotretinoin determined by dose limiting toxicities graded according to NCI CTCAE 4.0 (time frame: 21 days). 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 3 Apr 2018.