A Study of Belinostat + Carboplatin or Paclitaxel or Both in Patients With Ovarian Cancer in Need of Relapse Treatment

NCT00421889 | Completed Phase 1 Results

• 2 other identifiers: PXD101-CLN-8PXD101-040-EU
• Study Type: interventional
• Target: 80
• Locations: 3 countries
• Sites: 11

Brief Summary

The study seeks to assess the safety, pharmacodynamics, pharmacokinetics and efficacy of belinostat (PXD101) administered in combination with carboplatin or paclitaxel or both in patients with solid tumours followed by maximum tolerated dose (MTD) expansion (phase II) in ovarian and bladder cancer patients The clinical trial is now in the MTD (phase II) portion of the study enrolling bladder cancer patients. Enrollment of ovarian patients is complete.

Conditions

Ovarian Cancer; Epithelial Ovarian Cancer; Fallopian Tube Cancer; Bladder Cancer

Keywords

Ovarian cancer; Ovarian Neoplasms; Primary peritoneal; Epithelial ovarian; Fallopian tube; Bladder cancer; belinostat; PXD101; mixed mullerian cancer of ovarian origin

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerable Dose (MTD) Belinostat, Part A,

  To determine the maximum tolerated dose of belinostat (PXD101) in doses up to 1000 mg/m²/day administered in combination with standard doses of carboplatin (AUC of 5) and paclitaxel (175 mg/m2).

  Cycle 1

• Dose Limiting Toxicities (DLT), Part A

  To determine the number of participants experiencing dose limiting toxicities of belinostat (PXD101) in doses up to 1000 mg/m²/day administered in combination with standard doses of carboplatin and paclitaxel or both.

  Cycle 1

Secondary Outcomes (8)

• Best Overall Response (CR or PR)

  Throughout study until PD (progressive disease) or lost to follow up

• To Determine the Pharmacodynamic Effects of Belinostat (in the Combination) on Histone Acetylation in Peripheral Blood Mononuclear Cells (Selected Sites)

  Throughout the study

• Time to Progression

  Throughout study

• Time to Response

  Throughout study

• Duration of Response

  Throughout study

Study Arms (1)

Single arm

EXPERIMENTAL

Belinostat: 1000 mg/m2 days 1-5 in a 21 day cycle; IV Paclitaxel: Administered IV 2-3 hours after belinostat infusion on day 3 in a 21-day cycle Carboplatin: Administered IV infusion after paclitaxel on day 3 in a 21-day cycle

Drug: belinostat; Drug: Paclitaxel; Drug: Carboplatin

Interventions

belinostat DRUG

Also known as: PXD101

Single arm

Paclitaxel DRUG

Single arm

Carboplatin DRUG

Single arm

Eligibility Criteria

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

You may qualify if:

• Signed consent of an IRB (Institutional Review Board) approved consent form.
• Patients with histologically confirmed solid carcinomas, for which there is no known curative therapy.
• Performance status (Eastern Cooperative Oncology Group \[ECOG\]) ≤ 2.
• Life expectancy of at least 3 months.
• Age ≥ 18 years.
• Acceptable liver, renal and bone marrow function including the following:
• Bilirubin ≤ 1.5 times ULN (upper limit of normal).
• AST/SGOT (\[Aspartate Amino Transferase/Serum glutamic oxaloacetic transaminase\]), ALT/SGPT (\[Alanine Amino Transferase/Serum glutamic pyruvic transaminase\]) and alkaline phosphatase ≤ 3 times ULN (if liver metastases are present, then ≤ 5 x ULN is allowed).
• Measured EDTA (\[ethylenediaminetetraacetic acid\]) renal clearance ≥ 45 mL/min (EU sites). At the US sites calculated creatinine clearance ≥ 45 mL/min using the Jeliffe formula.
• Leukocytes \> 2.5×109/L, neutrophils \> 1.0x109/L, platelets \> 100×109/L.
• Hemoglobin \> 9.0 g/dL or \> 5.6 mmol/L.
• Acceptable coagulation status: PT-INR(\[prothrombin-International Normalized Ratio\])/APTT(\[Activated Partial Thromboplastin Time\]) ≤ 1.5 × ULN or in the therapeutic range if on anticoagulation therapy
• A negative pregnancy test for women of childbearing potential. For men and women of child-producing potential, the use of effective contraceptive methods during the study is required.
• Serum potassium within normal range (added in protocol Global version 3.0) Additional Eligibility Criteria at the MTD Expansion only
• Patients with epithelial ovarian cancer in need of relapse treatment. Changed with protocol Global version 3 to: Patients with epithelial ovarian, primary peritoneal, fallopian tube or mixed mullerian tumors of ovarian origin in need of relapse treatment.

You may not qualify if:

• Treatment with investigational agents within the last 4 weeks.
• Prior anticancer therapy within the last 3 weeks of study dosing including chemotherapy, radiotherapy, endocrine therapy, immunotherapy or use of other investigational agents. Changed with protocol Global version 1; prior anticancer therapy within the last 3 weeks of study dosing including chemotherapy, radiotherapy, endocrine therapy or immunotherapy.
• Co-existing active infection or any co-existing medical condition likely to interfere with study procedures, including significant cardiovascular disease (New York Heart Association Class III or IV cardiac disease), myocardial infarction within the past 6 months, unstable angina, congestive heart failure requiring therapy, unstable arrhythmia or a need for anti-arrhythmic therapy, or evidence of ischemia on ECG, marked baseline prolongation of QT/QTc interval, e.g., repeated demonstration of a QTc interval (\[corrected QT interval \]) \> 500 msec; Long QT Syndrome; the required use of concomitant medication on belinostat infusion days that may cause Torsade de Pointes (see Appendix 1.1, protocol EU version 1.0, Appendix A - Appendix 16.1.1).
• Altered mental status precluding understanding of the informed consent process and/or completion of the necessary studies.
• History of hypersensitivity to either platinum or paclitaxel that is unable to be desensitized (added with protocol Global version 4).
• More than 3 prior lines of chemotherapy given for metastatic disease (added with protocol Global version 1).
• Bowel obstruction or impending bowel obstruction.
• Known HIV positivity.
• Any Grade 2 or above drug-related neurotoxicity, following recovery.
• Changed with protocol Global version 1 to: Any existing Grade 2 or above drug related neurotoxicity due to prior treatment with agents causing neurotoxicity.
• Mixed mullerian tumors of intra-uterine origin, added with protocol Global version 3.

Sponsors & Collaborators

• Valerio Therapeutics: lead

Study Sites (11)

Gynecologic Oncology Associates

Newport Beach, California, 92663, United States

Location

Research Facility

Orlando, Florida, 32804, United States

Location

Hematology and Oncology Specialists, LLC

Covington, Louisiana, 70433, United States

Location

Hematology & Oncology Specialists, LLC

Metairie, Louisiana, 70006, United States

Location

Greater Baltimore Medical Center

Baltimore, Maryland, 21204, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Women & Infants Hospital of Rhode Island

Providence, Rhode Island, 02905, United States

Location

The Finsen Center, Rigshospitalet

Copenhagen, 2100, Denmark

Location

Research Facility, Herlev University Hospital

Herlev, 2730, Denmark

Location

The Beatson West of Scotland Cancer Centre

Glasgow, G120YN, United Kingdom

Location

The Royal Marsden NHS Trust

Surrey, SM2 5PT, United Kingdom

Location

MeSH Terms

Conditions

Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Fallopian Tube Neoplasms; Urinary Bladder Neoplasms

Interventions

belinostat; Paclitaxel; Carboplatin

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Fallopian Tube Diseases; Urologic Neoplasms; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

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

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 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2007
• First Posted: January 15, 2007
• Study Start: August 1, 2005
• Primary Completion: February 1, 2009
• Study Completion: February 1, 2009
• Last Updated: July 28, 2015
• Results First Posted: December 15, 2014

Record last verified: 2015-07

Locations

GB (2); US (7); DK (2)