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

Sponsor

Cellxpert Biotechnology Corp. (Industry)

Overall Status

Completed

CT.gov ID

NCT00103389

Collaborator

Medigen Biotechnology Corporation (Industry)

Enrollment

Locations

Arms

38.9

Duration (Months)

7.5

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Lung Cancer	Drug: PI-88 Drug: docetaxel	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

98 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Feb 1, 2004

Actual Primary Completion Date :

May 1, 2007

Actual Study Completion Date :

May 1, 2007

Arms and Interventions

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: PI-88 PI-88+docetaxel Drug: docetaxel docetaxel only

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: PI-88

PI-88+docetaxel

Drug: docetaxel

docetaxel only

Outcome Measures

Primary Outcome Measures

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

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 []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sydney Heamatology and Oncology Clinics	Hornsby	New South Wales	Australia	2077
2	Institute of Oncology at Prince of Wales Hospital	Randwick	New South Wales	Australia	2031
3	Royal North Shore Hospital	St. Leonards	New South Wales	Australia	2065
4	Sydney Cancer Centre at Royal Prince Alfred Hospital	Sydney	New South Wales	Australia	2050
5	Newcastle Mater Misericordiae Hospital	Waratah	New South Wales	Australia	2298
6	Princess Alexandra Hospital	Brisbane	Queensland	Australia	4102
7	Prince Charles Hospital	Chermside	Queensland	Australia	4032
8	Nambour General Hospital	Nambour	Queensland	Australia	4560
9	Mater Medical Centre	South Brisbane	Queensland	Australia	4101
10	Queen Elizabeth Hospital	Woodville	South Australia	Australia	5011
11	Alfred Hospital	Melbourne	Victoria	Australia	3004
12	Murray Valley Private Hospital and Cancer Treatment Centre	Wodonga	Victoria	Australia	3690
13	Sir Charles Gairdner Hospital - Perth	Perth	Western Australia	Australia	6009