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ThymomaPhase 2NCT00589290

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

A Phase 2 study testing Belinostat (PDX101) in people with Thymoma and Thymic Carcinoma, run by National Cancer Institute (NCI) at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Thymoma, Thymic Carcinoma
What is being tested?
Belinostat (PDX101)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
41 participants
Where
2 sitesUnited States
Study dates
Dec 2007to Jun 2014
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 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.
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  • 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.
  • Total bilirubin less than or equal to 1.5 times institutional upper limits of normal.
  • Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase(SGOT) and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase(SGPT) less than or equal to 3 times institutional upper limit of normal.
  • Creatinine less than or equal to 1.5 times institutional upper limits of normal or Calculated Creatinine greater than 45 mL/min/1.73 m^2 for patients with creatinine.
  • Clearance levels above institutional normal.
  • The effects of belinostat on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because histone deacetylase (HDAC) inhibitors are known to be teratogenic, 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 and continue for at least 2 months after completion. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with belinostat, breastfeeding should be discontinued if the mother is treated with belinostat.
  • Ability to comply with intravenous administration schedule, and the ability to understand and the willingness to sign a written informed consent document.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

  • Indiana University Cancer Center

    Indianapolis, Indiana, 46202-5262

Other trials in United States

About this study

Official title: A Multicenter Phase II Study of Belinostat (PXD-101) in Previously Chemotherapy Treated Thymoma and Thymic Carcinoma

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.
Read more

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.
Read the detailed description

Background:

Cisplatin-containing chemotherapy is the standard of care for advanced unresectable thymoma and thymic carcinoma. New options for treatment are necessary in patients with advanced thymoma and thymic carcinoma that have progressed on cisplatin-containing therapy. Histone deacetylase inhibitors have shown promising clinical activity in many malignancies. Belinostat, a potent histone deacetylase inhibitor, is a promising agent, which may have activity in patients with thymic malignancies.

Objectives:

  • To assess objective response rate according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria for belinostat monotherapy.
  • To assess safety of belinostat.
  • To evaluate time to response, duration of response, progression-free survival and overall survival.
  • To identify chromosomal gains or losses and gene methylation status by comparative genomic hybridization and methylation microarrays in thymoma / thymic carcinomas in relation to clinical outcome.
  • To assess expression levels of particular proteins on the pretreatment tumor sample, by immunohistochemistry (IHC) and correlate them with clinical outcome.
  • To identify and measure changes in p21 and protein hyperacetylation in peripheral blood mononuclear cells (PBMC), and vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in plasma and correlate them with clinical outcome.
  • To measure changes in modulation of T-cell function in peripheral blood lymphocytes.

Eligibility:

  • Patients with histologically confirmed thymic carcinoma or thymoma who have previously been treated on at least one platinum containing chemotherapy regimen.
  • Measurable disease by RECIST criteria.
  • Adequate renal, hepatic and hematopoietic function.
  • QT Interval must be less than 500 msec at baseline by electrocardiogram (EKG) (Fridericia's formula used for correction).
  • No major surgery, radiotherapy, or chemotherapy within 28 days of belinostat therapy.

Design:

  • Patients will receive belinostat as a 30-minute intravenous (IV) infusion of 1000 mg/m^2/day during days 1-5 every 3 weeks. After 12 cycles of treatment, cycles will be given every 4 weeks.
  • Treatment with belinostat alone will continue until disease progression.
  • Toxicity will be assessed every cycle by the Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 until December 31, 2010, and by CTCAE Version 4.0 beginning January 1, 2011.
  • Tumor response assessments by RECIST criteria will be performed every 2 cycles. After 12 cycles, response assessment will be every 3 cycles.
  • Correlative studies including comparative genomic hybridization, methylation microarray analysis, and tissue immunohistochemistry studies will be done on existing tumor blocks.
  • Blood samples for circulating plasma biomarkers of response including VEGF will be drawn the first day of cycle 1 and 2 as well as cycle 1, day 3.
  • Blood samples for protein hyperacetylation and T cell modulation analyses will be drawn the first day of cycle 1 and 2.
Being tested
Belinostat (PDX101)
Keywords
Histone deacetylase (HDAC) Inhibitors, Mediastinal Neoplasm, Thymic Carcinoma, Thymoma
Medical subject headings
Thymoma, Mediastinal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Belinostat (PDX101)Drug

    Also called PDX101

    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.

Study groups in NCT00589290
Study groupRoleWhat they receive
Belinostat TreatmentExperimental1000 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.
Receives: Drug: Belinostat (PDX101)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 25.5 months

  2. 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.

    Measured: 46 months

Secondary outcomes (1)

  1. Number of Participants With Adverse Events

    Here are the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.

    Measured: 26 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Jan 2008 (estimated)
  2. Study startDec 2007
  3. Primary completionJul 2013
  4. Study completionJun 2014

Resources

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
41 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00589290
Sponsor's protocol ID
080033
Other IDs
08-C-0033
Status last verified
Sep 2015
First submitted
25 Dec 2007
Last updated
30 Sep 2015
Data monitoring committee
No

Publications

  • 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.

    PubMed 16891859

  • 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.

    PubMed 17570676

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

    PubMed 15725919

  • 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.

    PubMed 21502553

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Belinostat (PDX101) in people with Thymoma and Thymic Carcinoma, run by National Cancer Institute (NCI) at 2 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 21 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 30 Sep 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 May 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Number of Participants With a Partial Response (time frame: 25.5 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00589290, which also lists 4 linked publications.

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 30 Sep 2015.

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