A Phase 1/2 Study of PXD101 (Belinostat) in Combination With Cisplatin, Doxorubicin and Cyclophosphamide in the First Line Treatment of Advanced or Recurrent Thymic, Malignancies

2014-07-23 21:09:35 | BioPortfolio



- Tumors of the thymus are rare and can be treated with surgery, but it is often difficult to determine whether a thymic tumor is malignant based on biopsy alone and the long-term survival rate is less than 50 percent. Because thymic tumors are so rare, most treatment knowledge comes from a relatively small series of cases, and the choice of treatment usually depends on the hospital or clinic staff's experience and familiarity with a given chemotherapy and surgery regimen.

- Belinostat is an investigational anticancer drug that has not yet been approved by the Food and Drug Administration for use in any cancer. Researchers are interested in determining whether belinostat can be combined with conventional chemotherapy to safely and effectively treat advanced thymic cancer.


- To determine a safe and tolerable dose of belinostat that can be given in combination with cisplatin, doxorubicin, and cyclophosphamide.

- To determine if belinostat (combined with the abovementioned standard chemotherapy regimen) is effective against thymic cancer cells.


- Individuals at least 18 years of age who have been diagnosed with advanced or recurrent thymic malignancy that is not considered to be curable with surgery or radiation therapy, and who have not received previous chemotherapy treatment.


- Participants will be screened with a physical exam, blood tests, and imaging studies as directed by the study researchers.

- Participants will receive six 21-day cycles (18 weeks) of treatment with belinostat in combination with cisplatin, doxorubicin, and cyclophosphamide. The treatment will require continuous infusion over 3 days, and participants will remain in the treatment center during this time. Participants will have regular blood tests, clinic visits, and imaging studies during the treatment period.

- Participants who complete the six treatment cycles with no severe side effects may be offered the option to continue treatment with belinostat alone.

- After the 18-week study period, participants will return for regular follow-up exams for at least 4 weeks, and will be asked to remain in contact with the study researchers once a year to continue to study long-term effects....



- New options for the treatment of patients with advanced thymoma and thymic carcinoma are needed.

- Belinostat, N-hydroxy-3-(phenylsulphamoylphenyl) acrylamide, is an hydroxamic acid deacetylase inhibitor that is able to inhibit both HDAC Class I and II enzymes.

- An ongoing phase II study of belinostat in recurrent or metastatic thymic malignancies has shown activity which warrants further consideration of belinostat in the first line.

- Belinostat alterations in target protein levels due to gene expression changes may allow increased sensitivity of cancer cells to conventional chemotherapy.


Primary Objectives

- In the Phase I portion the primary objective will be to determine a safe and tolerable phase 2 dose, DLTs and preliminary activity for the combination of belinostat by continuous IV infusion (CIVI) with cisplatin, doxorubicin and cyclophosphamide in patients with advanced thymic malignancies.

- In the Phase II portion the primary objective will be to determine the clinical response rate (PR+CR) of belinostat in combination with cisplatin, doxorubicin and cyclophosphamide in the first line treatment of patients with advanced thymic malignancies.

Secondary Objectives

- To determine time to response, duration of response, progression free survival (PFS) and overall survival (OS).

- To determine the toxicity profile and safety of this combination.

- To assess exploratory correlative markers in relation to response to treatment (immunohistochemistry and array CGH)


- Patients with histologically confirmed advanced thymic malignancies who are chemotherapy na ve.

- Measurable disease by RECIST criteria

- Adequate renal, hepatic and hematopoietic function


- The Phase I portion of the study will consist of four dose levels and dose escalations will follow according to traditional 3 patient cohorts.

- Once the maximum tolerated doe is determined, the phase II portion of the study will begin.

- Belinostat will be given as a 48h CIVI starting on day 1, doxorubicin as a slow IV injection on days 2 and 3, cisplatin will be infused over 1 hour on day 2 and cyclophosphamide as a slow IV infusion on Day 3.

- Treatment will be given every 21 days for no more than 6 cycles or until disease progression. Treatment with belinostat alone may continue until disease progression.

Study Design

Allocation: Non-Randomized, Control: Active Control, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment




Belinostat, Cisplatin, Cyclophosphamide, Doxorubicin


Indiana University
United States




National Institutes of Health Clinical Center (CC)

Results (where available)

View Results


Published on BioPortfolio: 2014-07-23T21:09:35-0400

Clinical Trials [2286 Associated Clinical Trials listed on BioPortfolio]

Chemotherapy Plus Cetuximab Followed by Surgical Resection in Patients With Locally Advanced or Recurrent Thymoma or Thymic Carcinoma

The main purpose of this study is to find out the good and the bad effects that the combination of cetuximab with the traditional chemotherapy regimen of cisplatin, doxorubicin, and cyclop...

Cisplatin vs. Doxorubicin/Cyclophosphamide in BrCa

This research study is a Phase II clinical trial. Phase II clinical trials test the effectiveness of an investigational drug, which is cisplatin in this trial, to learn how well it works i...

A Study of Belinostat With Dexamethasone, Cytarabine, Cisplatinum (RDHAP) Chemotherapy in Adults With Relapsed or Refractory Diffuse Large B-cell Lymphoma

The goal of this clinical research study is to find the highest tolerable dose of belinostat that can be combined with standard chemotherapy drugs (rituximab, cisplatin, cytarabine, and de...

Belinostat and Carboplatin in Treating Patients With Recurrent or Persistent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer That Did Not Respond to Carboplatin or Cisplatin

RATIONALE: Belinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as...

Palliative Treatment With Liposomal Doxorubicin Plus Cisplatin for Patients With Malignant Pleural Mesothelioma

Liposomal doxorubicin consists on doxorubicin encapsulated in liposomes that are composed of phosphatidylcholine and cholesterol. Liposomal doxorubicin can extravasate into tumors with a...

PubMed Articles [953 Associated PubMed Articles listed on BioPortfolio]

Adjuvant dose-dense doxorubicin-cyclophosphamide versus docetaxel-doxorubicin-cyclophosphamide for high-risk breast cancer: First results of the randomised MATADOR trial (BOOG 2004-04).

Dose-dense administration of chemotherapy and the addition of taxanes to anthracycline-based adjuvant chemotherapy have improved breast cancer survival substantially. However, clinical trials directly...

Extended pleurectomy decortication for thymoma with pleural dissemination.

Complete resection is the mainstay of treatment for thymoma. Even for advanced-stage thymoma with pleural dissemination, complete resection with extrapleural pneumonectomy may provide a favorable prog...

Mechanistic Study of Belinostat Oral Absorption from Spray Dried Dispersions.

Spray dried dispersions (SDDs) are an important technology for enhancing the oral bioavailability of poorly water-soluble drugs. To design an effective oral SDD formulation, the key rate-determining s...

Progressive peripheral CD8 T lymphocytosis complicated by pure red cell aplasia following immunosuppressive therapy for thymoma-associated myasthenia gravis.

We herein report a unique case of type B2 thymoma-associated myasthenia gravis which was ameliorated by immunosuppressive therapy in combination with chemotherapy. However, the patient subsequently de...

Ectopic hamartomatous thymoma (biphenotypic branchioma): A case report and review of the literature.

Ectopic hamartomatous thymoma is a very rare soft tissue neoplasm that commonly occurs in the lower neck of adult men.

Medical and Biotech [MESH] Definitions

A neoplasm originating from thymic tissue, usually benign, and frequently encapsulated. Although it is occasionally invasive, metastases are extremely rare. It consists of any type of thymic epithelial cell as well as lymphocytes that are usually abundant. Malignant lymphomas that involve the thymus, e.g., lymphosarcoma, Hodgkin's disease (previously termed granulomatous thymoma), should not be regarded as thymoma. (From Stedman, 25th ed)

An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.

Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer.

Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.

An anthracycline which is the 4'-epi-isomer of doxorubicin. The compound exerts its antitumor effects by interference with the synthesis and function of DNA.

More From BioPortfolio on "A Phase 1/2 Study of PXD101 (Belinostat) in Combination With Cisplatin, Doxorubicin and Cyclophosphamide in the First Line Treatment of Advanced or Recurrent Thymic, Malignancies"

Quick Search


Relevant Topics

Surgical treatments
Surgery is a technology consisting of a physical intervention on tissues. All forms of surgery are considered invasive procedures; so-called "noninvasive surgery" usually refers to an excision that does not penetrate the structure being exci...

Drug Discovery
Clinical Approvals Clinical Trials Drug Approvals Drug Delivery Drug Discovery Generics Drugs Prescription Drugs In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are dis...

Searches Linking to this Trial