Belinostat and Isotretinoin in Treating Patients With Solid Tumors That Are Metastatic or That Cannot Be Removed by Surgery

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

51 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-06-12

Study Completion Date

2018-03-29

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

MS-275 and Isotretinoin in Treating Patients With Metastatic or Advanced Solid Tumors or Lymphomas

NCT00098891

Adult Grade III Lymphomatoid Granulomatosis Anaplastic Large Cell Lymphoma Angioimmunoblastic T-cell Lymphoma +41 more

COMPLETED PHASE1

Isotretinoin in Preventing Skin Cancer

NCT00025012

Melanoma (Skin) Non-melanomatous Skin Cancer

COMPLETED NA

Isotretinoin in Treating Young Patients With High-Risk Neuroblastoma

NCT00939965

Neuroblastoma

UNKNOWN NA

Phase I Study of Isotretinoin in Patients With Recessive Dystrophic Epidermolysis Bullosa

NCT00014729

Epidermolysis Bullosa

COMPLETED PHASE1

Isotretinoin Plus Interferon in Treating Patients With Recurrent Cancer

NCT00002506

Cervical Cancer Esophageal Cancer Head and Neck Cancer +3 more

COMPLETED PHASE2

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

PRIMARY OBJECTIVES:

I. 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:

I. 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

See the medical conditions and disease areas that this research is targeting or investigating.

Adult Solid Neoplasm

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Treatment (belinostat, isotretinoin)

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.

Group Type EXPERIMENTAL

Belinostat

Intervention Type DRUG

Given IV

Isotretinoin

Intervention Type DRUG

Given orally

Pharmacological Study

Intervention Type OTHER

Correlative studies

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Belinostat

Given IV

Intervention Type DRUG

Isotretinoin

Given orally

Intervention Type DRUG

Pharmacological Study

Correlative studies

Intervention Type OTHER

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Beleodaq PXD 101 PXD101 13-cis retinoic acid 13-cis-Retinoate 13-cis-Retinoic Acid 13-cis-Vitamin A Acid 13-cRA Accure Accutane Amnesteem cis-Retinoic Acid Cistane Claravis Isotretinoinum Isotrex Isotrexin Neovitamin A Neovitamin A Acid Oratane Retinoicacid-13-cis Ro 4-3780 Ro-4-3780 Roaccutan Roaccutane Roacutan Sotret

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* 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
* 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

Exclusion Criteria

* 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
* 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

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Thehang Luu

Role: PRINCIPAL_INVESTIGATOR

City of Hope Comprehensive Cancer Center

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Site Status

USC / Norris Comprehensive Cancer Center

Los Angeles, California, United States

Site Status

University of California Davis Comprehensive Cancer Center

Sacramento, California, United States

Site Status

City of Hope South Pasadena

South Pasadena, California, United States

Site Status

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States