Chemotherapy in Treating Patients With Cancer of Unknown Primary Origin

A Randomized Phase III Trial of Paclitaxel, Carboplatin and Etoposide Vs. 5-Fluorouracil and Folinic Acid in the Treatment of Patients With Adenocarcinoma of Unknown Primary Site

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 may kill more tumor cells. It is not yet known which combination chemotherapy regimen is more effective for cancer of unknown primary origin.

PURPOSE: Randomized phase III trial to compare the effectiveness of two different regimens of combination chemotherapy in treating patients with cancer of unknown primary origin.

Study Overview

• Status: Unknown
• Conditions: Carcinoma of Unknown Primary
• Intervention / Treatment: Drug: carboplatin; Drug: fluorouracil; Drug: leucovorin calcium; Drug: etoposide; Drug: paclitaxel

Detailed Description

OBJECTIVES:

• Compare the overall survival after treatment with paclitaxel, carboplatin, and etoposide and after treatment with fluorouracil and leucovorin calcium in patients with adenocarcinoma of unknown primary.
• Compare the response rates, progression free survival, toxicity profile, and quality of life between the two regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified by center and presence or absence of liver metastases.

Patients are randomly assigned to one of two treatment arms.

• Arm I: Patients receive paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on day 1, and oral etoposide on days 1-10. Treatment is repeated every 3 weeks for up to four courses.
• Arm II: Patients receive leucovorin calcium IV over 2 hours followed by fluorouracil IV over 24 hours weekly for 6 weeks. Treatment is repeated every 7 weeks for up to two courses.

Patients are followed every 3 months after treatment for 1 year or until death. Quality of life questionnaires are completed at each follow-up.

PROJECTED ACCRUAL: Approximately 120-140 patients will be accrued for this study within 3 years.

• Study Type: Interventional
• Enrollment (Anticipated): 140
• Phase: Phase 3

Contacts and Locations

Study Locations

• Netherlands
  • Maastricht, Netherlands, 6202 AZ
    • Academisch Ziekenhuis Maastricht
  • Tilburg, Netherlands, 5022 GC
    • St. Elisabeth Ziekenhuis

Participation Criteria

Eligibility Criteria

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

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of any differentiation grade

  • Excludes the following "treatable" conditions:

    • Axillary node involvement
    • Peritonitis carcinomatosis
    • Blastic bone metastases and/or elevated PSA
    • Squamous cell cancer with cervical or inguinal presentation

    • Poorly differentiated carcinoma

      • Neuroendocrine tumors OR
      • Tumors located in the mediastinum, retroperitoneum, or nodes
• At least one measurable metastatic site
• No brain or meningeal metastases

PATIENT CHARACTERISTICS:

Age:

• Over 18

Performance status:

• ECOG 0-2

Hematopoietic:

• Leukocyte count at least 4,000/mm3
• Thrombocyte count at least 100,000/mm3

Hepatic:

• Bilirubin less than 1.4 mg/dL
• AST and ALT less than 3 times upper limit of normal
• No cirrhosis of the liver

Renal:

• Creatinine less than 1.7 mg/dL

Cardiovascular:

• At least 3 months since myocardial infarction
• No congestive heart failure, tachydysrhythmia, or unstable angina pectoris

Other:

• Not pregnant or nursing
• Negative pregnancy test
• No active infection
• No other serious illness or medical condition
• No current or prior malignancy except nonmelanomatous skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 4 weeks since prior radiotherapy (no greater than 25% of bone marrow)

Surgery:

• Not specified

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized

Collaborators and Investigators

• Sponsor: Academisch Ziekenhuis Maastricht
• Investigators: Study Chair: R. L. Jansen, MD, PhD, Academisch Ziekenhuis Maastricht

Study record dates

Study Major Dates

• Study Start: August 1, 1998

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): August 7, 2013
• Last Update Submitted That Met QC Criteria: August 6, 2013
• Last Verified: February 1, 2003

More Information

Terms related to this study

• Keywords: newly diagnosed carcinoma of unknown primary; adenocarcinoma of unknown primary
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplastic Processes; Neoplasm Metastasis; Carcinoma; Neoplasms, Unknown Primary; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Protective Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Micronutrients; Vitamins; Calcium-Regulating Hormones and Agents; Antidotes; Vitamin B Complex; Carboplatin; Etoposide; Paclitaxel; Fluorouracil; Leucovorin; Calcium; Levoleucovorin
• Other Study ID Numbers: DUT-KWF-CKVO-9801; CDR0000066622 (Registry Identifier: PDQ (Physician Data Query)); EU-98023