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

NCT00873119 | Completed Phase 2 Results

• 1 other identifier: PXD101-CLN-17
• Study Type: interventional
• Target: 89
• Locations: 4 countries
• Sites: 23

Brief Summary

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.

Conditions

Carcinoma of Unknown Primary

Keywords

Belinostat; PXD101; Carboplatin; Paclitaxel; CUP; Carcinoma of unknown primary; Occult primary

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  Time from the date of randomization to the time of disease progression or death due to any cause, measured by RECIST criteria (Response Evaluation Criteria In Solid Tumors).

  Tumor assessment every 6 weeks for the treatment period. Subsequent assessments every 6 weeks for the initial 6 months, then every 9 weeks for 6 months, then every 12 weeks for 12 months and then every 6 months until 5 years from the start of study

Secondary Outcomes (5)

• Best Overall Response

  Tumor assessment every 6 weeks for the treatment period. Subsequent assessments every 6 weeks for the initial 6 months, then every 9 weeks for 6 months, then every 12 weeks for 12 months and then every 6 months until 5 years from the start of study

• Overall Survival (OS)

  Tumor assessment every 6 weeks for the treatment period. Subsequent assessments every 6 weeks for the initial 6 months, then every 9 weeks for 6 months, then every 12 weeks for 12 months and then every 6 months until 5 years from the start of study

• Time to Response

  Tumor assessment every 6 weeks for the treatment period. Subsequent assessments every 6 weeks for the initial 6 months, then every 9 weeks for 6 months, then every 12 weeks for 12 months and then every 6 months until 5 years from the start of study

• Duration of Response

  Tumor assessment every 6 weeks for the treatment period. Subsequent assessments every 6 weeks for the initial 6 months, then every 9 weeks for 6 months, then every 12 weeks for 12 months and then every 6 months until 5 years from the start of study

• Time to Progression (TTP)

  Tumor assessment every 6 weeks for the treatment period. Subsequent assessments every 6 weeks for the initial 6 months, then every 9 weeks for 6 months, then every 12 weeks for 12 months and then every 6 months until 5 years from the start of study

Study Arms (2)

Arm A - BelCaP

EXPERIMENTAL

Group A: belinostat 1000 mg/m² 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 2000 mg administered orally once daily on days 4 and 5, every 3-weeks, in combination with paclitaxel 175 mg/m² administered as an IV infusion following the infusion of belinostat on cycle day 3, and carboplatin (AUC 6) administered as a 30-60 minute IV infusion directly after the paclitaxel administration on cycle day 3.

Drug: belinostat, carboplatin, paclitaxel

Arm B - CaP

ACTIVE COMPARATOR

Group B: paclitaxel 175 mg/m² administered as an IV infusion directly followed by carboplatin (AUC 6) administered as a 30-60 minute IV infusion on cycle day 1 of a 3-weekly cycle.

Drug: carboplatin, paclitaxel

Interventions

belinostat, carboplatin, paclitaxel DRUG

Also known as: PXD101, Belinostat, Carboplatin, Paclitaxel, Taxol

Arm A - BelCaP

carboplatin, paclitaxel DRUG

Also known as: Carboplatin, Paclitaxel, Taxol

Arm B - CaP

Eligibility Criteria

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

You may qualify if:

• Patients with CUP where the primary site had not been revealed by complete history, physical examination (including gynecological examination when appropriate), computed tomography (CT) 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.
• Signed consent of an IRB (\[Institutional Review Board\])/IEC (\[Independent ethics committee\]) approved ICF (\[Informed Consent Form\]).
• At least one measurable lesion according to RECIST (\[response evaluation criteria in solid tumors \]) criteria. Note, target lesions could only be selected within previously irradiated areas if newly arising or clearly progressing after irradiation as proven by repeat scanning
• Performance status Eastern Cooperative Oncology Group (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.
• Serum potassium within normal range.
• Acceptable coagulation status: Prothrombin time/International normalized ratio PT/INR (\[international normalized ratio\]), and activated partial thromboplastin time (APTT) ≤ 1.5 × upper limit of normal (ULN) or in the therapeutic range if on anticoagulation therapy.
• Acceptable liver, renal and bone marrow function including the following:
• Bilirubin ≤ 1.5 times ULN (if liver metastases were present, then ≤ 3 × ULN was allowed).
• Aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT), alanine amino transferase/serum glutamic pyruvic transaminase (ALT/SGPT), and alkaline phosphatase ≤ 3 times ULN (if liver metastases were present, then ≤ 5 × ULN was allowed).
• An estimated creatinine clearance ≥ 45 mL/min using an appropriate formula (Appendix C, protocol version 1.0, Appendix 16.1.1), or measured ethylenediaminetetraacetic acid (EDTA) renal clearance ≥ 45 mL/min.
• Absolute neutrophils count ≥ 1.5 × 109/L, platelets ≥ 100 × 109/L.
• Hemoglobin ≥ 9.0 g/dL or ≥ 5.6 mmol/L (patients with chronic anemia due to underlying disease and its treatment could undergo blood transfusion prior to treatment in order to meet this criteria).

You may not qualify if:

• Patients with well recognized subsets of CUP site where treatments directed towards a defined tumor type, or surgery, alternatively radiotherapy, can be advised:
• Women with adenocarcinoma involving only axillary lymph nodes.
• Women with papillary serous carcinoma of the peritoneum.
• Women with adenocarcinoma with positive staining for estrogen receptor (ER) or progesterone receptor.
• Young men (\< 45 years) with poorly differentiated carcinoma consistent with an extragonadal germ cell tumor (carcinoma involving mediastinum or retroperitoneum, or elevated levels of beta-human chorionic gonadotropin or alpha-fetoprotein).
• Men with bone metastases and/or adenocarcinoma, and abnormally elevated PSA (\[Prostate specific antigen\]) in their plasma.
• Patients with squamous cell carcinoma involving only cervical lymph nodes, or inguinal lymph nodes.
• Patients with neuroendocrine carcinomas determined according to standard pathology diagnosis procedures, including stains.
• Patients with potentially completely resectable metastatic disease, or disease which can be adequately treated with radiotherapy only.
• 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, could be enrolled. If clinical suspicion, adequate investigations should be performed to rule out brain metastases or meningeal involvement.
• Prior systemic anti-tumor therapy, including chemotherapy administered in association to radiotherapy for sensitization, for CUP. Note, prior radiotherapy or surgery was allowed provided treatment was completed at least 4 weeks before randomization.
• Treatment with investigational agents, including non-anti-tumor agents, within the last 4 weeks before randomization.
• Co-existing active severe infection or any co-existing medical condition assessed by the Investigator as likely to interfere with study procedures.
• Significant cardiovascular disease (New York Heart Association Class III or IV cardiac disease), myocardial infarction within the past 6 months, unstable angina, unstable arrhythmia or a need for anti-arrhythmic therapy (use of medication to control heart rate in patients with atrial fibrillation was allowed, if on stable medication for at least the last month prior to randomization and the medication not listed as causing Torsade de Points (Section 13.2, Appendix B, protocol version 1.0, Appendix 16.1.1), or evidence of acute ischemia on ECG.
• Marked baseline prolongation of QT/QTc (\[corrected QT interval\]) interval, i.e., demonstration of a QTc interval \> 450 millisecond (ms); Long QT Syndrome; the required use of concomitant medication that may cause Torsade de Pointes (Section 13.2, Appendix B, protocol version 1.0, Appendix 16.1.1).

Sponsors & Collaborators

• Valerio Therapeutics: lead
• Spectrum Pharmaceuticals, Inc: collaborator

Study Sites (23)

Florida Cancer Specialists

Fort Myers, Florida, 33619, United States

Location

Northwest Georgia Oncology Centers

Marietta, Georgia, 30060, United States

Location

Baton Rouge Medical Center

Baton Rouge, Louisiana, 70809, United States

Location

Center for Cancers and Blood Disorders

Bethesda, Maryland, 20817, United States

Location

Research Medical Center

Kansas City, Missouri, 64132, United States

Location

Oncology Hematology Care Inc.

Cincinnati, Ohio, 45242, United States

Location

South Carolina Oncology Associates

Columbia, South Carolina, 29210, United States

Location

Chattanooga Oncology & Hematology Associates, PC

Chattanooga, Tennessee, 37404, United States

Location

Tennessee Oncology Sarah Cannon Research

Nashville, Tennessee, 37203, United States

Location

South Texas Oncology and Hematology

San Antonio, Texas, 78258, United States

Location

Virginia Cancer Institute

Richmond, Virginia, 23230, United States

Location

H:S Rigshospital, The Finsen Centre

Copenhagen, DK-2100, Denmark

Location

CRLCC Francois Baclesse, Oncologie medicale

Caen, 14000, France

Location

Centre Oscar Lambert

Lille, 59020, France

Location

Centre Léon Bérard, Oncologie

Lyon, 69008, France

Location

Centre Eugène Marquis

Rennes, 35042, France

Location

Centre Henri Becquerel, Oncologie Médicale

Rouen, 76038, France

Location

Institut de Cancerologie de la Loire

Saint-Priest-en-Jarez, 42270, France

Location

Institut Gustave Roussy IGR

Villejuif, 94805, France

Location

Carl-Gustav-Carus Medicinische Klinik und Poliklinik I

Dresden, 01307, Germany

Location

Kliniken Essen-Mitte

Essen, 45136, Germany

Location

ASKLEPIOS Klinik Altona

Hamburg, 22763, Germany

Location

Ostholstein-Onkologie

Oldenburg in Holstein, 23758, Germany

Location

MeSH Terms

Conditions

Neoplasms, Unknown Primary

Interventions

belinostat; Carboplatin; Paclitaxel; CP protocol

Condition Hierarchy (Ancestors)

Neoplasm Metastasis; Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Results Point of Contact

• Title: PRS Administrator Gunilla Emanuelson
• Organization: Topotarget A/S

enquiries@topotarget.com

+45 39 17 83 92

Study Officials

• e-mail contact via enquires@topotarget.com

  Valerio Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 31, 2009
• First Posted: April 1, 2009
• Study Start: February 1, 2009
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: July 28, 2015
• Results First Posted: December 9, 2014

Record last verified: 2015-07

Locations

FR (7); US (11); DK (1); DE (4)