Hydroxyurea Plus Combination Chemotherapy in Patients With Non-small Cell Lung Cancer

PHASE I TRIAL OF HYDROXYUREA FOR SALVAGE OF INCURABLE NON-SMALL CELL LUNG CANCER

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug is a way to kill more tumor cells.

PURPOSE: Phase I trial to study the effects of hydroxyurea plus combination chemotherapy in patients with non-small cell lung cancer.

Study Overview

• Status: Unknown
• Conditions: Lung Cancer
• Intervention / Treatment: Drug: etoposide; Drug: cisplatin; Drug: hydroxyurea; Drug: vinorelbine tartrate; Drug: vinblastine sulfate; Drug: vindesine; Procedure: drug resistance inhibition treatment

Detailed Description

OBJECTIVES: I. Estimate the maximum tolerated dose of hydroxyurea that can be given in combination with other chemotherapy regimens in patients with incurable non-small cell lung cancer. II. Determine the toxicity of this combination chemotherapy regimen in these patients. III. Observe the efficacy of hydroxyurea in patients with incurable non-small cell lung cancer refractory to front-line chemotherapy.

OUTLINE: This study seeks to estimate the maximum tolerated dose (MTD) of hydroxyurea in combination with other chemotherapy. Groups of 3 patients take escalated doses of oral hydroxyurea three times weekly or daily throughout treatment with cisplatin plus (per their previous regimen) vinblastine, vindesine, vinorelbine, or etoposide. Treatment continues in responding and stable patients until 3 months beyond documentation of complete remission (minimum 4 courses), maximum of 6 courses beyond documentation of partial remission, or 3 courses beyond documentation of stable disease. Patients are followed every 3 weeks for 3 months, every 6 weeks for 3 months, then every 3 months until disease progression.

PROJECTED ACCRUAL: An anticipated 15-30 patients will be entered.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1H 1C4
      • Ottawa Regional Cancer Centre - General Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS: Histopathologically proven non-small cell lung cancer that is incurable by surgery or radiotherapy Brain metastases allowed Demonstrated resistance to prior chemotherapy required by 1 of the following: Tumor growth or recurrence while on treatment Failure of tumor to shrink over 3 consecutive courses of treatment Measurable or evaluable disease

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Zubrod 0-2 Life expectancy: Greater than 12 weeks Hematopoietic: ANC at least 1,500 Platelets at least 100,000 Hemoglobin at least 10 g/dL Hepatic: Bilirubin less than 1.5 mg/dL (26 micromoles/L) AST/ALT less than 1.5 times normal Renal: Creatinine less than 1.6 mg/dL (150 micromoles/L) Cardiovascular: No uncontrolled hypertension or other cardiac disease No myocardial infarction within 6 months Other: No uncontrolled diabetes No active abuse of ethanol No allergies to study medication No active infection or other serious medical condition that precludes protocol treatment No dementia or significantly altered mental status that precludes informed consent No prior melanoma or malignancy of the following sites: Breast Kidney Thyroid Salivary glands Endometrium No other second malignancy within 5 years except: Nonmelanomatous skin cancer Carcinoma in situ of cervix No pregnant or nursing women Effective contraception required of fertile women

PRIOR CONCURRENT THERAPY: Recovery from any treatment-limiting toxicity required Biologic therapy: Not specified Chemotherapy: At least 3 weeks since myelosuppressive chemotherapy (6 weeks since nitrosoureas, mitomycin, or high-dose carboplatin) Endocrine therapy: Not specified Radiotherapy: At least 3 weeks since radiotherapy unless to a limb or limited treatment area Surgery: Not specified

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: Ottawa Regional Cancer Centre
• Investigators: Study Chair: David J. Stewart, MD, FRCPC, Ottawa Regional Cancer Centre

Study record dates

Study Major Dates

• Study Start: July 1, 1995

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: March 25, 2004
• First Posted (Estimate): March 26, 2004

Study Record Updates

• Last Update Posted (Estimate): September 17, 2013
• Last Update Submitted That Met QC Criteria: September 16, 2013
• Last Verified: October 1, 2001

More Information

Terms related to this study

• Keywords: recurrent non-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; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antisickling Agents; Etoposide; Cisplatin; Vinorelbine; Hydroxyurea; Vinblastine; Vindesine
• Other Study ID Numbers: CDR0000065207; CAN-OTT-9501; NCI-V96-1099