Lepirudin in Treating Patients With Recurrent or Advanced Small Cell Lung Cancer

A Phase I/II Study of Recombinant Desulfato Hirudin, Lepirudin (Refludan) in Small Cell Lung Cancer Patients Previously Treated With Chemotherapy

RATIONALE: Anticoagulants, such as lepirudin, may help prevent blood clots from forming in patients who have received chemotherapy for small cell lung cancer.

PURPOSE: This phase I/II trial is studying the side effects and best dose of lepirudin in treating patients with recurrent or advanced small cell lung cancer.

Study Overview

• Status: Terminated
• Conditions: Lung Cancer
• Intervention / Treatment: Biological: lepirudin

Detailed Description

OBJECTIVES: I. Determine the dose, safety, and antitumor response rate of lepirudin in patients with recurrent or extensive stage small cell lung cancer previously treated with chemotherapy.

OUTLINE: This is a dose escalation (in individual patients) study. Patients receive dose escalated lepirudin subcutaneously once or twice a day for 3-4 days. Dose escalation continues in each patient until aPTT prolongation occurs or the maximum dose level is reached. The patient then continues treatment on the maximum tolerated dose. Treatment continues in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 20-35 patients will be accrued for this study within 18-24 months.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Norris Cotton Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

1. Pathologically confirmed recurrent or extensive stage small cell lung cancer.
2. Received at least one prior chemotherapy regimen
3. Measurable or evaluable disease that has not been irradiated
4. No pleural effusions, bone metastases, brain metastases, elevated serum enzymes, or radionuclide scans as the sole indicator lesion
5. Brain metastases allowed if patients received cranial irradiation and have no clinical evidence of brain metastases

PATIENT CHARACTERISTICS:

1. Age: Not specified
2. Performance status: Karnofsky 60-100%
3. Life expectancy: Not specified
4. Hematopoietic: WBC at least 3,000/mm3 Platelet count at least 100,000/mm3
5. Hepatic: Bilirubin no greater than 2.0 mg/dL PT and aPTT normal
6. Renal: Creatinine no greater than 1.5 mg/dL OR Creatinine clearance greater than 60 mL/min
7. Cardiovascular: No unstable heart rhythm No unstable angina No clinical evidence of congestive heart failure No prior cerebrovascular accident or stroke No uncontrolled or severe hypertension
8. Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception
9. At least 6 weeks since any signs or symptoms of bleeding No history of bleeding disorder
10. No bacterial endocarditis or other active infection

PRIOR CONCURRENT THERAPY:

1. Biologic therapy: Not specified
2. Chemotherapy: At least 3 weeks since prior chemotherapy
3. Endocrine therapy: Not specified Radiotherapy: At least 3 weeks since prior radiotherapy
4. Surgery: At least 6 weeks since major surgery, trauma, or needle biopsy of any organ
5. Other: No concurrent anticoagulant or platelet inhibitor therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lepirudin; Dose level 1: 10 mg once daily -> (total dose, 10 mg/d) Dose level 2: 15 mg once daily -> (total dose, 15 mg/d) Dose level 3: 10 mg twice daily -> (total dose, 20 mg/d) Dose level 4: 15 mg twice daily -> (total dose, 30 mg/d) Dose level 5. 20 mg twice daily -> (total dose, 40 mg/d) Dose level 6: 25 mg twice daily -> (total dose, 50 mg/d)	Biological: lepirudin; lepirudin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose, Safety and Antitumor Response Rate of Administering Recombinant Desulfato Hirudin, Elpirudin to Previously Treated Patients With Extensive or Recurrent Small Cell Lung Cancer	Evaluated through clinical exams, tumor assessments, laboratory assessment, and adverse event assessments.	18 months

Collaborators and Investigators

• Sponsor: Dartmouth-Hitchcock Medical Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: James R. Rigas, MD, Norris Cotton Cancer Center

Study record dates

Study Major Dates

• Study Start: November 1, 1998
• Primary Completion (Actual): July 1, 2001
• Study Completion (Actual): July 1, 2001

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: April 30, 2004
• First Posted (Estimate): May 3, 2004

Study Record Updates

• Last Update Posted (Estimate): August 8, 2016
• Last Update Submitted That Met QC Criteria: June 27, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: extensive stage small cell lung cancer; recurrent small cell lung cancer
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Fibrinolytic Agents; Fibrin Modulating Agents; Protease Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Lepirudin
• Other Study ID Numbers: D9815; P30CA023108 (U.S. NIH Grant/Contract); DMS-9815 (Other Identifier: Dartmouth-Hitchcock Medical Center); NCI-V98-1512 (Other Identifier: NCI)