Docetaxel With or Without PI-88 in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer

A Phase II Study of Docetaxel With PI-88 in Patients With Advanced Non-Small-Cell Lung Cancer

RATIONALE: Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. PI-88 may stop the growth of non-small cell lung cancer by blocking blood flow to the tumor. It may also help docetaxel work better by making tumor cells more sensitive to the drug. Giving docetaxel together with PI-88 may kill more tumor cells. It is not yet known whether giving docetaxel together with PI-88 is more effective than docetaxel alone in treating non-small cell lung cancer.

PURPOSE: This randomized phase II trial is studying docetaxel and PI-88 to see how well they work when given together compared to docetaxel alone in treating patients with stage IIIB or stage IV non-small cell lung cancer.

Study Overview

• Status: Completed
• Conditions: Lung Cancer
• Intervention / Treatment: Drug: docetaxel; Drug: PI-88

Detailed Description

OBJECTIVES:

Primary

• Compare the safety and efficacy of docetaxel with vs without PI-88 in patients with stage IIIB or IV non-small cell lung cancer.

Secondary

• Determine the efficacy markers of docetaxel and PI-88 in these patients.
• Determine the safety and potential efficacy of PI-88 alone as maintenance therapy in patients whose disease has been controlled with docetaxel and PI-88 combination therapy.
• Determine the safety and potential efficacy of PI-88 alone as third-line therapy in these patients.

OUTLINE: This is an open-label, randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive docetaxel IV over 1 hour on days 1, 8, and 15.
• Arm II: Patients receive docetaxel as in arm I. Patients also receive PI-88 subcutaneously once daily on days 1-4, 8-11, and 15-18.

In both arms, treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients in arm II with stable or responding disease after 6 courses may continue to receive PI-88 alone as maintenance therapy. Patients in arm I with progressive disease or unacceptable toxicity before the completion of 6 courses may receive PI-88 alone as third-line therapy.

PROJECTED ACCRUAL: Approximately 100 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 98
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Hornsby, New South Wales, Australia, 2077
      • Sydney Heamatology and Oncology Clinics
    • Randwick, New South Wales, Australia, 2031
      • Institute of Oncology at Prince of Wales Hospital
    • St. Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital
    • Sydney, New South Wales, Australia, 2050
      • Sydney Cancer Centre at Royal Prince Alfred Hospital
    • Waratah, New South Wales, Australia, 2298
      • Newcastle Mater Misericordiae Hospital
  • Queensland
    • Brisbane, Queensland, Australia, 4102
      • Princess Alexandra Hospital
    • Chermside, Queensland, Australia, 4032
      • Prince Charles Hospital
    • Nambour, Queensland, Australia, 4560
      • Nambour General Hospital
    • South Brisbane, Queensland, Australia, 4101
      • Mater Medical Centre
  • South Australia
    • Woodville, South Australia, Australia, 5011
      • Queen Elizabeth Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Alfred Hospital
    • Wodonga, Victoria, Australia, 3690
      • Murray Valley Private Hospital and Cancer Treatment Centre
  • Western Australia
    • Perth, Western Australia, Australia, 6009
      • Sir Charles Gairdner Hospital - Perth

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 116 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Diagnosis of non-small cell lung cancer

  • Stage IIIB or IV disease

• Eligible for second-line docetaxel

  • Disease progression during or after completion of prior first-line therapy comprising radiotherapy and/or platinum-based chemotherapy

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• At least 2 months

Hematopoietic

• Neutrophil count > 1,500/mm^3
• Platelet count > 100,000/mm^3
• WBC > 3,000/mm^3
• No history of thrombotic thrombocytopenic purpura or other platelet disease

Hepatic

• Bilirubin normal
• ALT and AST ≤ 2.5 times upper limit of normal (ULN) (1.5 times ULN if alkaline phosphatase > 2.5 times ULN)
• Alkaline phosphatase ≤ 5 times ULN (unless bone metastases are present)
• PT < 1.5 times ULN
• Activated PTT normal

Renal

• Creatinine clearance or glomerular filtration rate > 50mL/min

Cardiovascular

• None of the following within the past 3 months:

  • Myocardial infarction
  • Stroke
  • Congestive heart failure

Immunologic

• No history of immune-mediated thrombocytopenia
• No evidence of anti-heparin antibodies
• No history of allergy and/or hypersensitivity to anti-coagulants or thrombolytic agents, especially heparin
• No history of allergy to polysorbate 80
• No uncontrolled or serious infection within the past 4 weeks

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics
• No prior docetaxel

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• More than 3 months since prior radiotherapy to > 30% of marrow-bearing bone
• Concurrent local palliative radiotherapy allowed

Surgery

• More than 4 weeks since prior major surgery

Other

• More than 4 weeks since prior antineoplastic therapy
• More than 2 weeks since prior and no concurrent heparin or low-molecular weight heparin
• More than 4 weeks since prior investigational therapy
• No concurrent aspirin or aspirin-containing medications except low-dose aspirin (≤ 100 mg/day)
• No concurrent nonsteroidal anti-inflammatory drugs except cyclooxygenase-2 inhibitors
• No concurrent warfarin or warfarin-containing medications except low-dose warfarin (≤ 1 mg/day)

• No concurrent antiplatelet drugs, including any of the following:

  • Abciximab
  • Clopidogrel
  • Dipyridamole
  • Ticlopidine
  • Tirofiban

• No concurrent drugs that may inhibit docetaxel metabolism, including any of the following:

  • Cyclosporine
  • Terfenadine
  • Ketoconazole
  • Erythromycin
  • Troleandomycin
• No other concurrent investigational drugs
• No other concurrent antineoplastic therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: docetaxel; treated with docetaxel alone	Drug: docetaxel; docetaxel only
Experimental: PI-88+docetaxel; treated with docetaxel and PI-88	Drug: docetaxel; docetaxel only; Drug: PI-88; PI-88+docetaxel

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Proportion of patients who are progression-free as measured by Response Evaluation Criteria in Solid Tumors (RECIST) v2.0 at 6 months
Non-progression rate as measured by RECIST v2.0 at 6 months

Secondary Outcome Measures

Outcome Measure
Time to progression as measured by RECIST v2.0 at baseline, and then week 4 of courses 2, 3, 4, and 6
Response rate as measured by RECIST v2.0 at baseline, and then week 4 of courses 2, 3, 4, and 6
Quality of life as measured by Lung Cancer Symptom Scale (LCSS) every month
Overall survival as measured by RECIST v2.0 at death

Collaborators and Investigators

• Sponsor: Cellxpert Biotechnology Corp.
• Collaborators: Medigen Biotechnology Corporation
• Investigators: Study Chair: Nick Pavlakis, MD, Royal North Shore Hospital

Study record dates

Study Major Dates

• Study Start: February 1, 2004
• Primary Completion (Actual): May 1, 2007
• Study Completion (Actual): May 1, 2007

Study Registration Dates

• First Submitted: February 7, 2005
• First Submitted That Met QC Criteria: February 7, 2005
• First Posted (Estimate): February 8, 2005

Study Record Updates

• Last Update Posted (Actual): June 27, 2022
• Last Update Submitted That Met QC Criteria: June 21, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: recurrent non-small cell lung cancer; stage IIIB non-small cell lung cancer; stage IV 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; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel
• Other Study ID Numbers: PROGEN-PR88202; CDR0000409568 (Registry Identifier: PDQ (Physician Data Query)); AUS-RNSH-0309-183M

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No