Belinostat, Carboplatin and Paclitaxel (BelCaP) Compared to Carboplatin and Paclitaxel in Patients With Cancer of Unknown Primary

This study has been completed.
Sponsor:
Collaborator:
Spectrum Pharmaceuticals, Inc
Information provided by (Responsible Party):
TopoTarget A/S
ClinicalTrials.gov Identifier:
NCT00873119
First received: March 31, 2009
Last updated: December 18, 2013
Last verified: December 2013
  Purpose

The purpose of this study is to assess efficacy and safety of belinostat in combination with carboplatin and paclitaxel in patients with previously untreated carcinoma of unknown primary.


Condition Intervention Phase
Occult Primary
Drug: belinostat, carboplatin, paclitaxel
Drug: carboplatin, paclitaxel
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label Randomized Phase II Trial of Belinostat (PXD101) in Combination With Carboplatin and Paclitaxel (BelCaP) Compared to Carboplatin and Paclitaxel in Patients With Previously Untreated Carcinoma of Unknown Primary

Resource links provided by NLM:


Further study details as provided by TopoTarget A/S:

Primary Outcome Measures:
  • Progression Free Survival measured by RECIST criteria [ Time Frame: May 2010 ] [ Designated as safety issue: No ]

Enrollment: 89
Study Start Date: February 2009
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
Group A: belinostat administered as a 30 minute IV infusion once daily on days 1, 2 and 3, with at least 18 hours between infusions, followed by belinostat administered orally once daily on days 4 and 5, every 3-weeks, in combination with paclitaxel administered as an IV infusion following the infusion of belinostat on cycle day 3, and carboplatin administered as a 30-60 minute IV infusion directly after the paclitaxel administration on cycle day 3.
Drug: belinostat, carboplatin, paclitaxel
Belinostat 1000 mg/m² IV infusion once daily for days 1+2+3 followed by belinostat 2000 mg PO on days 4+5 every 3 weeks in combination with carboplatin (AUC 6) IV infusion directly after paclitaxel (175 mg/m²) IV on day 3
Other Names:
  • PXD101, Belinostat
  • Carboplatin
  • Paclitaxel, Taxol
Active Comparator: B
Group B: paclitaxel administered as an IV infusion directly followed by carboplatin administered as a 30-60 minute IV infusion on cycle day 1 of a 3-weekly cycle.
Drug: carboplatin, paclitaxel
Paclitaxel 175 mg/m² IV infusion followed by carboplatin (AUC 6) on day 1 of a 3-weekly cycle
Other Names:
  • Carboplatin
  • Paclitaxel, Taxol

Detailed Description:

This is an open-label, multinational, multicenter, randomized, comparative efficacy and safety study in previously untreated patients with carcinoma of unknown primary. Patients meeting inclusion and exclusion criteria will be randomized to treatment within either of two study groups:

  • Group A: belinostat administered as a 30 minute IV infusion once daily on days 1, 2 and 3 followed by belinostat administered orally once daily on days 4 and 5, every 3-weeks, in combination with paclitaxel administered as an IV infusion following the infusion of belinostat on cycle day 3, and carboplatin administered as a 30-60 minute IV infusion directly after the paclitaxel administration on cycle day 3.
  • Group B: paclitaxel administered as an IV infusion directly followed by carboplatin administered as a 30-60 minute IV infusion on cycle day 1 of a 3-weekly cycle.

Approximately 44 patients will be randomized to each group (in total 88 patients) over a planned recruitment period of 15 months. Patients will be treated in three week cycles for up to 6 cycles of chemotherapy containing treatment unless there is disease progression or treatment-related toxicities that are not manageable with dose-reduction schemes allowed per protocol or by other appropriate supportive measures. After 6 cycles of treatment, patients in Group A will continue treatment on belinostat monotherapy administered orally once daily on days 1 to 14, every 3-weeks until disease progression or treatment-related toxicities.

Toxicity will be monitored continuously during study treatment and 30 days following last study drug administration. Safety will be assessed by adverse events and laboratory tests, graded according to the NCI CTC (version 3.0).

Tumor assessments according to RECIST will be made by appropriate radiologic imaging techniques at baseline and by the same techniques every 6 weeks for the initial 6 months, then every 9 weeks for the next 6 months, then every 12 weeks for a further 12 months, and then every 6 months until 5 years from the start of study treatment cycle 1. When tumor assessments stop, survival follow-up will be carried out every 3 months for the initial 2 years, and then every 6 months until 5 years from the start of study treatment cycle 1.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Include

  • Patients with carcinoma of unknown primary where the primary site had not been revealed by complete history, physical examination (including gynecological examination when appropriate), computed tomography scan of the chest, abdomen and pelvis, bilateral mammography (in women with adenocarcinoma or poorly differentiated carcinoma), routine laboratory studies (complete blood cell counts, electrolytes, urinalysis, liver and renal function tests), and directed work-up of any other symptomatic areas.
  • Light microscopic pathologic diagnosis of adenocarcinoma (including poorly differentiated), squamous cell carcinoma, or poorly differentiated carcinoma.
  • Signed consent of an IRB/Ethics committee approved informed consent form.
  • At least one measurable lesion according to RECIST criteria.
  • Performance status (ECOG) ≤ 2.
  • Age ≥ 18 years.
  • A negative serum or urine pregnancy test for women of childbearing potential. Postmenopausal women must have been amenorrheic for ≥ 12 months to be considered of non-childbearing potential.
  • Acceptable liver, renal and bone marrow function.

Exclusion Criteria:

Include

  • Patient with well recognized subsets of carcinoma of unknown primary site where treatments directed towards a defined tumor type, or surgery, alternatively radiotherapy, can be advised.
  • Patients with brain or meningeal metastases. Note, patients with adequately treated brain metastases, e.g. surgically resected, or adequately controlled by radiotherapy, with no residual neurological symptoms due to metastases and no steroid treatment required, can be enrolled.
  • Prior systemic anti-tumor therapy, including chemotherapy administered in association to radiotherapy for sensitization, for the carcinoma of unknown primary. Note, prior radiotherapy or surgery is allowed provided treatment was completed at least 4 weeks before randomization.
  • Co-existing active severe infection or any co-existing medical condition assessed by the investigator as likely to interfere with trial procedures.
  • Significant cardiovascular disease
  • History of a previous malignancy within 5 years with the exception of non-metastatic non-melanoma skin cancer or cervical carcinoma in situ. Prior systemic therapy for other malignancy completed at least 5 years before randomization is allowed.
  • Known infection with HIV, or known active Hepatitis B or C infection.
  • Peripheral neuropathy ≥ Grade 2.
  • Pregnant, or lactating, females.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00873119

Locations
United States, Florida
Florida Cancer Specialists
Fort Myers, Florida, United States, 33619
United States, Georgia
Northwest Georgia Oncology Centers
Marietta, Georgia, United States, 30060
United States, Louisiana
Baton Rouge Medical Center
Baton Rouge, Louisiana, United States, 70809
United States, Maryland
Center for Cancers and Blood Disorders
Bethesda, Maryland, United States, 20817
United States, Missouri
Research Medical Center
Kansas City, Missouri, United States, 64132
United States, Ohio
Oncology Hematology Care Inc.
Cincinnati, Ohio, United States, 45242
United States, South Carolina
South Carolina Oncology Associates
Columbia, South Carolina, United States, 29210
United States, Tennessee
Chattanooga Oncology & Hematology Associates, PC
Chattanooga, Tennessee, United States, 37404
Tennessee Oncology Sarah Cannon Research
Nashville, Tennessee, United States, 37203
United States, Texas
South Texas Oncology and Hematology
San Antonio, Texas, United States, 78258
United States, Virginia
Virginia Cancer Institute
Richmond, Virginia, United States, 23230
Denmark
H:S Rigshospital, The Finsen Centre
Copenhagen, Denmark, DK-2100
France
CRLCC Francois Baclesse, Oncologie medicale
Caen, France, 14000
Centre Oscar Lambert
Lille, France, 59020
Centre Léon Bérard, Oncologie
Lyon, France, 69008
Centre Eugène Marquis
Rennes cedex, France, 35042
Centre Henri Becquerel, Oncologie Médicale
Rouen, France, 76038
Institut de Cancerologie de la Loire
Saint Priest en Jarez, France, 42270
Institut Gustave Roussy IGR
Villejuif cedex, France, 94805
Germany
Carl-Gustav-Carus Medicinische Klinik und Poliklinik I
Dresden, Germany, 01307
Kliniken Essen-Mitte
Essen, Germany, 45136
ASKLEPIOS Klinik Altona
Hamburg, Germany, 22763
Ostholstein-Onkologie
Oldenburg in Holstein, Germany, 23758
Sponsors and Collaborators
TopoTarget A/S
Spectrum Pharmaceuticals, Inc
Investigators
Principal Investigator: Seaborn Wade, MD Virginia Cancer Institute - USA
Principal Investigator: John Hainsworth, MD Tennessee Oncology Sarah Cannon Research Institute - USA
Principal Investigator: Gerdt Hübner, MD Ostholstein-onkologie-Onkologische Schwerpunktpraxis - Germany
Principal Investigator: Michael Stahl, MD Kliniken Essen-Mitte - Germany
Principal Investigator: Karim Fizazi, MD Institut Gustave Roussy IGR - France
Principal Investigator: Pascal Seve, MD Hôpital de l'Hôtel-Dieu - Lyon, France
Principal Investigator: Thierry Lesimple, MD Comprehensive Cancer Center Eugène Marquis - Rennes Cedex, France
Principal Investigator: Gedske Daugaard, MD H:S Rigshospitalet, Department of Oncology - Denmark
Principal Investigator: James Rubinsak, MD Florida Cancer Specialists - USA
Principal Investigator: Djelila Allouache, MD Centre Francois Baclesse - Caen, France
Principal Investigator: Edward Arrowsmith, MD Chattanooga Oncology & Hematology Associates, PC - USA
Principal Investigator: Christelle De La Fouchardiere, MD Centre Léon Bérard - Lyon, France
Principal Investigator: Marianne Leheurteur, MD Centre Henri Becquerel - Rouen, France
Principal Investigator: Christian Meyer zum Büschenfelde, MD ASKLEPIOS Klinik Altona - Hamburg, Germany
Principal Investigator: Nicolas Penel, MD Centre Oscar Lambret, Lille, France
Principal Investigator: Fred Kudrik, MD South Carolina Oncology Associates, SC, USA
Principal Investigator: Robert Herman, MD Northwest Georgia Oncology Centers, P.C. USA
Principal Investigator: Gladys Rodriquez, MD South Texas Oncology and Hematology, San Antonio, USA
Principal Investigator: Irfan Firdaus, MD Oncology Hematology Care, Inc, Cincinnati, USA
Principal Investigator: Ralph Boccia, MD Center for Cancers and Blood disorders, Bethesda, USA
Principal Investigator: Michael Castine, MD Baton
Principal Investigator: Jaswinder Singh Research Medical Center, Kansas City, USA
Principal Investigator: Gunnar Folprecht, MD Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden, Germany
Principal Investigator: Yacine Merrouche, Prof Institut de Cancerologie de la Loire
  More Information

No publications provided

Responsible Party: TopoTarget A/S
ClinicalTrials.gov Identifier: NCT00873119     History of Changes
Other Study ID Numbers: PXD101-CLN-17
Study First Received: March 31, 2009
Last Updated: December 18, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by TopoTarget A/S:
Belinostat
PXD101
Carboplatin
Paclitaxel
CUP
Carcinoma of unknown primary
Occult primary

Additional relevant MeSH terms:
Paclitaxel
Belinostat
Carboplatin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Histone Deacetylase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 22, 2014