Fondaparinux (Arixtra) With Chemotherapy for Advanced Non-Small Cell Lung Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Francisco Robert,MD, University of Alabama at Birmingham
ClinicalTrials.gov Identifier:
NCT00476216
First received: May 16, 2007
Last updated: March 3, 2014
Last verified: March 2014
  Purpose

There is a direct association between cancer and thrombosis (blood clots). The purpose of this study is to determine the best dose of an antithrombotic (prevents blood clots) agent called fondaparinux in non-small cell lung cancer(NSCLC). Patients will also receive chemotherapy.


Condition Intervention Phase
Non-Small Cell Lung Cancer
Venous Thromboembolism
Drug: Combination of Arixtra with chemotherapy
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Feasibility Study of the Combination of Fondaparinux (Arixtra) With Chemotherapy in Patients With Advanced Non-Small Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by University of Alabama at Birmingham:

Primary Outcome Measures:
  • The tolerability and safety of the combination of fondaparinux with standard chemotherapy (carboplatin/paclitaxel). [ Time Frame: Every 3 weeks prior to each cycle of therapy. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Clinically evident Venous Thromboembolism (VTE) [ Time Frame: Every 3 weeks prior to each cyle of therapy. ] [ Designated as safety issue: Yes ]

Enrollment: 23
Study Start Date: September 2007
Study Completion Date: December 2013
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Combination of Arixtra with chemotherapy
Carboplatin 6 AUC q 21 days; Paclitaxel 200 mg/m2 q 21 days. Cohort I: Arixtra 2.5 mg SQ qd x 21 days; Cohort II: Arixtra weight-based dose (D1-2)followed by Arixtra 2.5 SQ q day (D3-21)
Drug: Combination of Arixtra with chemotherapy

Single arm, 2 cohort feasibility study:

Carboplatin will be administered intravenously over approximately 30 minutes after paclitaxel infusion is completed and the dose will be calculated on basis of an area under the curve (AUC) of 6, according to the formula administered every 21 days. Paclitaxel will be administered 200 mg/m2 over 3 hours every 21 days.

Patients in both cohorts 1 & 2 will receive standard chemotherapy alone during cycle 1.

Cohort 1:During subsequent cycles (2-4) patients will receive a daily prophylactic dose (day 1 through 21) of Arixtra and continue 21 days after the last course of chemotherapy.

Cohort 2: Patients in cohort 2 will receive standard chemotherapy alone during cycle 1. During subsequent cycles, the patient will receive a therapeutic weight based dose of Arixtra for the first 2 days of each chemotherapy cycle followed by a daily prophylactic dose of Arixtra (day 3 through 21) until the next course of chemotherapy.

Other Name: Fondaparinux

Detailed Description:

This is a single center, open-labeled, single arm phase 1 feasibility study in patients with newly diagnosed stage IV NSCLC. To evaluate the change in the biologic parameters measured, two cohorts of patients will receive altered dosing regimens of fondaparinux starting with the second cycle of chemotherapy. The biologic parameters measured during the first cycle of chemotherapy will serve as a control for each patient. Chemotherapy consists of 3-week cycles of carboplatin and paclitaxel. The absolute maximum length of therapy with fondaparinux will be 3 months, regardless of which cohort the patient is assigned.

This study consists of 2 cohorts:

Cohort 1:

Patients in cohort 1 will receive standard chemotherapy alone during cycle 1. During subsequent cycles (2-4) patients will receive a daily prophylactic dose (day 1 through 21) of fondaparinux. The anticoagulation will continue 21 days after the last course of chemotherapy.

Cohort 2:

Patients in cohort 2 will receive standard chemotherapy alone during cycle 1. During subsequent cycles, the patient will receive a therapeutic weight based dose of fondaparinux for the first 2 days of each chemotherapy cycle followed by a daily prophylactic dose of fondaparinux (day 3 through 21) until the next course of chemotherapy.

  Eligibility

Ages Eligible for Study:   18 Years to 79 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologic or cytologic diagnosis of Non-Small Cell Lung Cancer.
  • Stage IV Non-Small Cell Lung Cancer.
  • Measurable or assessable tumor parameters according to RECIST criteria.
  • ECOG Performance Status 0-2.
  • Age between 18 and 79 years (in the State of Alabama > 18).
  • Adequate hematologic, coagulation, liver and renal function, defined as:
  • Absolute neutrophil count (ANC) ≥ 1500/µL
  • Platelet count ≥ 100,000/µL
  • Serum Glutamic Oxaloacetic Transaminase(SGOT)/Serum Glutamic Pyruvic Transaminase(SGPT) ≤ 2.5 x upper limit of normal or ≤ 5 x upper limit of normal when liver metastases are present
  • Total bilirubin value ≤ 1.5 x upper limit of normal
  • Serum creatinine value ≤ 1.5 x upper limit of normal
  • Normal prothrombin time and partial thromboplastin time
  • Fully recovered from any previous surgery (at least 4 weeks since major surgery).
  • Must have recovered from prior radiation therapy (at least 3 weeks).
  • All participants must agree to practice approved methods of birth control (if applicable). A negative pregnancy test must be documented during the screening period for women of childbearing potential.
  • Must provide written informed consent and authorization to use and disclose health information.
  • No prior chemotherapy.

Exclusion Criteria:

  • Active bleeding disorder.
  • Evidence of hemoptysis. Patients with blood-tinged or blood-streaked sputum will be permitted on study if the hemoptysis amounts to less than 5 mL of blood per episode and less than 10 mL of blood per 24-hour period in the best estimate of the investigator.
  • Previous history of Venous Thromboembolism (VTE) within 12 months and requiring active anticoagulation therapy.
  • Concurrent cancer chemotherapy, biologic therapy or radiotherapy.
  • Administration of any investigational drug within 28 days prior to administration of the current therapy.
  • Symptomatic brain metastases; those patients should be treated first with either whole brain radiation therapy or radiosurgery and have stable disease.
  • Concurrent serious infection.
  • Concomitant severe or uncontrolled underlying medical disease unrelated to the tumor, which is likely to compromise patient safety and affect the outcome of the study.
  • History of other malignancy (except non-melanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission and off all therapy for a minimum of 2 years.
  • Any evidence or history of hypersensitivity or other contraindications for the drugs used in this trial.
  • Psychiatric disorder that prevents patients from providing informed consent or following protocol instructions.
  • Pregnant or lactating women.
  • Creatinine clearance < 30 mL/min.
  • Patient body weight < 50 kg.
  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: NCT00476216

Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35233
Sponsors and Collaborators
University of Alabama at Birmingham
Investigators
Principal Investigator: Francisco Robert, M.D. University of Alabama at Birmingham
  More Information

No publications provided

Responsible Party: Francisco Robert,MD, Professor of Medicine, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT00476216     History of Changes
Other Study ID Numbers: F070309006, UAB 0649
Study First Received: May 16, 2007
Last Updated: March 3, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Alabama at Birmingham:
Non-Small Cell Lung Cancer
Venous Thromboembolism
VTE
Arixtra

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Thromboembolism
Venous Thromboembolism
Venous Thrombosis
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Thrombosis
Fondaparinux
PENTA
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents

ClinicalTrials.gov processed this record on August 28, 2014