Belinostat (PXD101) to Treat Tumors of the Thymus at an Advanced Stage

NCT00589290 | Completed Phase 2 Results

• 2 other identifiers: 08003308-C-0033
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 2

Brief Summary

Background:

• Cisplatin-containing chemotherapy is the standard treatment for advanced tumors of the thymus that cannot be removed surgically.
• New treatment options are needed for patients with advanced tumors of the thymus that do not improve with cisplatin-containing therapy.
• Belinostat is a drug that inhibits enzymes called histone deacetylase. Histone deacetylase inhibitors have shown promising activity in many cancers and may be useful in treating patients with thymic tumors. Objectives:
• To assess the safety and effectiveness of belinostat for treatment of malignant thymic tumors in patients who failed after standard treatment. Eligibility:
• Patients 18 years of age or older with an advanced thymic tumor that has progressed after treatment with platinum-containing chemotherapy. Design:
• Patients receive belinostat treatment in 21-day cycles. The drug is given as an infusion through a vein during days 1 through 5 of each cycle. Treatment cycles continue as long as the medicine is tolerated and the cancer does not worsen.
• Patients have a physical examination and several blood tests during every cycle.
• Patients have an electrocardiogram every cycle before starting the belinostat infusion and again on the last day of the infusion.
• Patients undergo computed tomography (CT) or other imaging test, such as ultrasound or MRI, every two cycles to evaluate the response of the tumor to treatment.
• Tumor tissue obtained from a previous biopsy is used for research purposes.

Conditions

Thymoma; Thymic Carcinoma

Keywords

Histone deacetylase (HDAC) Inhibitors; Mediastinal Neoplasm; Thymic Carcinoma; Thymoma

Outcome Measures

Primary Outcomes (2)

• Number of Participants With a Partial Response

  Response is defined by the Response Evaluation Criteria in Solid Tumor (RECIST). Partial response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. For additional details about the RECIST criteria see the protocol Link module.

  25.5 months

• Chromosomal Gains or Losses in Comparative Genomic Hydridization in Thymoma and Thymic Cancer

  Utilize a patients tumor tissue to determine if there is any correlation between chromosomal gains or losses in comparative genomic hybridization in thymoma and thymic carcinomas and clinical outcomes.

  46 months

Secondary Outcomes (1)

• Number of Participants With Adverse Events

  26 months

Study Arms (1)

Belinostat Treatment

EXPERIMENTAL

1000 mg/m\^2/day as a 30 minute intravenous (IV) infusion daily for 5 days every 3 weeks (day 1-5 of the 3 week treatment cycle). After 12 cycles of treatment, cycles will be given for 5 days every 4 weeks.

Drug: Belinostat (PDX101)

Interventions

Belinostat (PDX101) DRUG

1000 mg/m\^2/day as a 30 minute intravenous (IV) infusion daily for 5 days every 3 weeks (day 1-5 of the 3 week treatment cycle). After 12 cycles of treatment, cycles will be given for 5 days every 4 weeks.

Also known as: PDX101

Belinostat Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed invasive recurrent or metastatic thymoma or thymic carcinoma by the pathology department / Center for Cancer Research (CCR) / National Cancer Institute (NCI).
• Patients must have had at least one prior platin-containing chemotherapy regimen. There is no limit to the number of prior chemotherapy regimens received. Progressive disease should have been documented before entry into the study.
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as greater than 20 mm with conventional techniques or as greater than 10 mm with spiral computed tomography (CT) scan.
• Patients must have recovered from toxicity related to prior therapy to at least to grade 1 (defined by the Common Terminology Criteria for Adverse Events (CTCAE) 3.0 until December 31, 2010, and by CTCAE 4.0 beginning January 1, 2011) and must not have had prior chemotherapy within 4 weeks. Patients must be at least 28 days since any prior radiation or major surgery.
• Target lesions cannot be selected within previously irradiated areas, if not newly arising or clearly progressing after irradiation as proven by repeat scanning.
• Concurrent corticosteroids for myasthenia gravis, or other paraneoplastic syndromes, or other chronic conditions are allowed.
• Age greater than 18 years.
• Life expectancy of greater than 3 months.
• Performance status (Eastern Cooperative Oncology Group (ECOG)) less than or equal to 2.
• Patients must have adequate organ and marrow function (as defined below). Patients must have returned to base line or grade one from any acute toxicity related to prior therapy.
• Laboratory Test/Required Value:
• Absolute neutrophil count greater than 1,500/microl.
• Platelets greater than 100,000/microl.
• International normalized ratio (INR) less than or equal to 1.5 times upper limit of normal (ULN) or
• Partial thromboplastin time (PTT) abnormality can be explained by the presences of lupus anticoagulant or in the therapeutic range if on anticoagulation.

You may not qualify if:

• Patients with symptomatic brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. However, patients who have had treatment for their brain metastases and whose brain metastatic disease status has remained stable for at least 3 months without steroids may be enrolled at the discretion of the principal investigator.
• Uncontrolled medical illness including, but not limited to, ongoing or uncontrolled, symptomatic congestive heart failure (American Heart Association (AHA) Class II or worse), uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Marked baseline prolongation of Q wave, T wave (QT)/corrected QT(QTc) interval, e.g., repeated demonstration of a QTc interval greater than 500 msec (Fridericia's formula used for correction); Long QT Syndrome. Any concomitant medication that may cause QTc prolongation, induce Torsades de Pointes.
• Human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with belinostat.(HIV) positive patients not receiving antiretroviral therapy are excluded due to the possibility that belinostat may worsen their condition and the likelihood that the underlying condition may obscure the attribution of adverse events with respect to belinostat.
• Patients may not be receiving any other investigational agents.
• History of another invasive malignancy in the last five years. Adequately treated non-invasive, non-melanoma skin cancers as well as in situ carcinoma of the cervix will be allowed.
• Prior treatment with drugs of the HDAC inhibitor class.
• Patients with tumor amenable to potentially curative therapy as assessed by the investigator.
• Subjects with resectable tumors would not be eligible for the study.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

Indiana University Cancer Center

Indianapolis, Indiana, 46202-5262, United States

Location

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Giaccone G, Wilmink H, Paul MA, van der Valk P. Systemic treatment of malignant thymoma: a decade experience at a single institution. Am J Clin Oncol. 2006 Aug;29(4):336-44. doi: 10.1097/01.coc.0000227481.36109.e7.

  PMID: 16891859 BACKGROUND

• Wright CD. Management of thymomas. Crit Rev Oncol Hematol. 2008 Feb;65(2):109-20. doi: 10.1016/j.critrevonc.2007.04.005. Epub 2007 Jun 14.

  PMID: 17570676 BACKGROUND

• Giaccone G. Treatment of malignant thymoma. Curr Opin Oncol. 2005 Mar;17(2):140-6. doi: 10.1097/01.cco.0000152628.43867.8e.

  PMID: 15725919 BACKGROUND

• Giaccone G, Rajan A, Berman A, Kelly RJ, Szabo E, Lopez-Chavez A, Trepel J, Lee MJ, Cao L, Espinoza-Delgado I, Spittler J, Loehrer PJ Sr. Phase II study of belinostat in patients with recurrent or refractory advanced thymic epithelial tumors. J Clin Oncol. 2011 May 20;29(15):2052-9. doi: 10.1200/JCO.2010.32.4467. Epub 2011 Apr 18.

  PMID: 21502553 RESULT

Related Links

• NIH Clinical Center Detailed Web Page
• Medline Plus
• Drug Information
• United States Food \& Drug Administration Resources
• RECIST

MeSH Terms

Conditions

Thymoma; Mediastinal Neoplasms

Interventions

belinostat

Condition Hierarchy (Ancestors)

Neoplasms, Complex and Mixed; Neoplasms by Histologic Type; Neoplasms; Thymus Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lymphatic Diseases; Hemic and Lymphatic Diseases; Mediastinal Diseases; Thoracic Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Arun Rajan, M.D.
• Organization: National Institutes of Health (NIH), National Cancer Institute (NCI)

rajana@mail.nih.gov

301-594-5322

Study Officials

• Giuseppe Giaccone, M.D.

  National Cancer Institute, National Institutes of Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 25, 2007
• First Posted: January 9, 2008
• Study Start: December 1, 2007
• Primary Completion: July 1, 2013
• Study Completion: June 1, 2014
• Last Updated: September 30, 2015
• Results First Posted: May 30, 2012

Record last verified: 2015-09

Locations

US (2)