Safety/Efficacy Study of a Drug to Reduce Thrombocytopenia in Patients Receiving Chemotherapy for Ovarian, Fallopian Tube or Peritoneal Cancer

This study has been terminated.
(Insufficient incidence of thrombocytopenia in control population)
Sponsor:
Collaborator:
Tarix Pharmaceuticals
Information provided by (Responsible Party):
US Biotest, Inc.
ClinicalTrials.gov Identifier:
NCT00771810
First received: October 9, 2008
Last updated: April 30, 2013
Last verified: April 2013
  Purpose

This research study will investigate the safety and effectiveness of two different dose levels of a new, unapproved drug to be given along with the chemotherapy regimens gemcitabine and carboplatin or gemcitabine and cisplatin prescribed to women for the treatment of ovarian cancer. This experimental drug is called TXA127 and is being tested for effectiveness to see if it will help reduce some of the side effects of the chemotherapy, primarily low blood platelet levels that lead to excess bleeding. This study also intends to test the safety of TXA127 when given as an injection under the skin on a daily basis concurrently with up to 6 cycles of the prescribed chemotherapy.


Condition Intervention Phase
Thrombocytopenia
Neutropenia
Lymphopenia
Anemia
Drug: TXA127
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
Official Title: Phase IIb Study Evaluating the Safety and Efficacy of TXA127 in the Reduction of Incidence and Severity of Thrombocytopenia in Patients Receiving Combination Gemcitabine and Platinum Therapy for Ovarian, Fallopian Tube, or Peritoneal Carcinoma

Resource links provided by NLM:


Further study details as provided by US Biotest, Inc.:

Primary Outcome Measures:
  • Chemotherapy Cycles During Which the Platelet Count Measures Below 50,000/mm3 [ Time Frame: During a maximum of six 3-week chemotherapy cycles ] [ Designated as safety issue: No ]
    Mean percentage of cycles with platelet counts below 50,000/mm3


Secondary Outcome Measures:
  • Subjects With Platelet Counts Below 50,000/mm3 [ Time Frame: During a maximum of six 3-week chemotherapy cycles ] [ Designated as safety issue: No ]
    Number of subjects who experienced a platelet count below 50,000/mm3

  • Treatment Cycles With Platelets Counts Below 25,000/mm3 [ Time Frame: During a maximum of six 3-week chemotherapy cycles ] [ Designated as safety issue: No ]
    Mean percentage of treatment cycles where platelets counts were below 25,000/mm3

  • Chemotherapy Dose Intensity and Dose Density [ Time Frame: During a maximum of six 3-week chemotherapy cycles ] [ Designated as safety issue: No ]
    Mean percentage of cycles where projected (target) chemotherapy dose was maintained

  • Lymphopenia as Determined by Lymphocyte Count [ Time Frame: During a maximum of six 3-week chemotherapy cycles ] [ Designated as safety issue: No ]
    Number of subjects with a treatment emergent adverse event of lymphopenia

  • Neutropenia [ Time Frame: During a maximum of six 3-week chemotherapy cycles ] [ Designated as safety issue: No ]
    Number of subjects with a treatment emergent adverse event of neutropenia

  • Anemia [ Time Frame: During a maximum of six 3-week chemotherapy cycles ] [ Designated as safety issue: No ]
    Number of subjects with a treatment emergent adverse event of anemia

  • Mucositis [ Time Frame: During a maximum of six 3-week chemotherapy cycles ] [ Designated as safety issue: No ]
    Number of subjects with a treatment emergent adverse event of mucositis

  • Alopecia [ Time Frame: During a maximum of six 3-week chemotherapy cycles ] [ Designated as safety issue: No ]
    Number of subjects with a treatment emergent adverse event of alopecia

  • Rescue Treatment for Hematopoiesis and Mucositis [ Time Frame: During a maximum of six 3-week chemotherapy cycles ] [ Designated as safety issue: No ]

    Number of subjects with a treatment emergent adverse event of hematopoiesis and mucositis who received rescue treatment as determined by the administration of:

    1. Transfusions
    2. Filgrastim or Pegfilgrastim
    3. Erythropoietin
    4. Palifermin


Enrollment: 34
Study Start Date: October 2008
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Combination gemcitabine and platinum-based chemotherapy with concurrent placebo
Drug: Placebo
Once daily subcutaneous injection of placebo
Experimental: TXA127 100 ug/kg
Combination gemcitabine and platinum-based chemotherapy with concurrent 100 ug/kg/day TXA127
Drug: TXA127
Once daily subcutaneous injection of 100 ug/kg
Other Name: Angiotensin 1-7
Experimental: TXA127 300 ug/kg
Combination gemcitabine and platinum-based chemotherapy with concurrent 300 ug/kg/day TXA127
Drug: TXA127
Once daily subcutaneous injection of 300 ug/kg
Other Name: Angiotensin 1-7

Detailed Description:

This is a Phase IIb, multicenter, randomized, double-blind, placebo-controlled study comparing safety and efficacy of two dose levels of TXA127 when administered during 6 cycles of combination gemcitabine and platinum-based chemotherapy. This study intends to investigate the effectiveness of TXA127 for the mitigation of severity and/or incidence of thrombocytopenia, as well as safety when administered as a self-injected, subcutaneous solution.

Females 18 years of age or older with a confirmed diagnosis of ovarian carcinoma who are scheduled to undergo combination chemotherapy with gemcitabine and carboplatin or gemcitabine and cisplatin will be considered for this study. Subjects may be chemotherapy naïve, newly diagnosed, or post a single course of chemotherapy followed by a progression- and treatment-free interval of at least 3 months, or post 2 or more previous courses of chemotherapy after a progression- and treatment-free interval of at least 6 months.

Subjects will be randomized in a 1:1:1 ratio to one of the following three blinded treatment groups: placebo, 100 ug/kg/day TXA127 and 300 ug/kg/day TXA127.

Treatment will be concurrent with up to six consecutive 21-day cycles of one of the following gemcitabine and platin regimens:

Regimen A

  • Intravenous cisplatin therapy at a dose of 30-50 mg/m2 given on Day 1 of the cycle
  • Intravenous gemcitabine at a dose of 800 mg/m2 given on Day 1 after cisplatin and on Day 8 of the cycle.

Regimen B

  • Intravenous gemcitabine at a dose of 1000 mg/m2 given on Days 1 and 8 of the cycle
  • Intravenous carboplatin AUC 4 given after gemcitabine on Day 1 of the cycle

TXA127 will be self-administered as a subcutaneous injection by the subject once daily on Days 2-6 and 9-15 during each cycle of chemotherapy. Blood specimens will be drawn for hematologic analysis on Days 1, 8 and 15 of each treatment cycle.

  Eligibility

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

Inclusion Criteria:

  • Females at least 18 years of age with ovarian carcinoma who are one of the following:

    • Newly diagnosed with ovarian cancer and chemotherapy naïve, or
    • Post a single previous course of chemotherapy, with a 3-month disease-progression and treatment-free interval, with the exception of antibody therapy, prior to the study screening visit, or
    • Post two or more previous courses of chemotherapy with a 6-month disease-progression and treatment-free interval, with the exception of antibody therapy, prior to the study screening visit.
  • Must be scheduled for a course of combination chemotherapy consisting of gemcitabine and cisplatin or gemcitabine and carboplatin to be administered in 21-day cycles
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
  • Adequate bone marrow, renal, and hepatic functions as measured by standard chemistry and hematology blood tests
  • Adequate blood coagulation parameters as measured by standard blood tests for coagulation

Exclusion Criteria:

  • Any clinical or laboratory abnormality greater than Grade 2 toxicity (NCI criteria), with the exception of laboratory parameters specified in the inclusion criteria
  • Significant unstable cardiovascular disease
  • Uncontrolled high blood pressure
  • Current use of an angiotensin converting enzyme (ACE) inhibitor or angiotensin II antagonists
  • Evidence of metastatic disease to the bone
  • Metastatic disease to the CNS requiring treatment or radiation therapy
  • Uncontrolled infection(s)
  • Radiation therapy or chemotherapy (except as specified in the inclusion criteria) within the previous 5 years
  • Concurrent use of hematopoietic or erythropoietic agents
  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: NCT00771810

Locations
United States, Alabama
University of Southern Alabama Mitchell Cancer Institute
Mobile, Alabama, United States, 36604
United States, California
USC - LAC Medical Center
Los Angeles, California, United States, 90033
University of California - Irvine, Chao Family Comprehensive Cancer Center
Orange, California, United States, 92868
United States, Illinois
Rush University Medical Center
Chicago, Illinois, United States, 60612
United States, Kansas
Associates in Women's Health
Wichita, Kansas, United States, 67208
United States, New York
Schwartz Gynecologic Oncology, PLLC
Brightwaters, New York, United States, 11718
Sponsors and Collaborators
US Biotest, Inc.
Tarix Pharmaceuticals
Investigators
Study Director: Gere S diZerega, MD US Biotest, Inc.
  More Information

Publications:
Responsible Party: US Biotest, Inc.
ClinicalTrials.gov Identifier: NCT00771810     History of Changes
Other Study ID Numbers: TXA127-2007-002
Study First Received: October 9, 2008
Results First Received: February 25, 2013
Last Updated: April 30, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by US Biotest, Inc.:
Ovarian Cancer
Thrombocytopenia
Cytopenia
Chemotherapy

Additional relevant MeSH terms:
Anemia
Lymphopenia
Neutropenia
Thrombocytopenia
Hematologic Diseases
Leukopenia
Leukocyte Disorders
Immunologic Deficiency Syndromes
Immune System Diseases
Agranulocytosis
Blood Platelet Disorders
Gemcitabine
Angiotensin I (1-7)
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Antihypertensive Agents
Cardiovascular Agents
Vasodilator Agents

ClinicalTrials.gov processed this record on August 01, 2014