Phase II Study of Aerosolized Liposomal 9-Nitro-20 (S)- Camptothecin (L9NC)

NCT ID: NCT00249990

Last Updated: 2010-01-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 39 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-04-30
• Study Completion Date: 2007-09-30

Brief Summary

The purposes of this study are:

1.1 To determine the efficacy of liposomal 9-Nitro-20 (S)-Camptothecin (L9NC) administered by aerosolization to patients with metastatic endometrial cancer.

1.2 To determine toxicity profile of L9NC administered by aerosolization for 5 consecutive days per week X 8 weeks, every 10 weeks.

1.3 To perform a pharmacology study of L9NC in the plasma and the lungs after aerosolization. A specific protocol will be written for this part.

Detailed Description

RATIONALE: Camptothecin (CPT) is a plant alkaloid isolated from Camptotheca acuminata in 1966. As a topoisomerase I inhibitor, it has powerful anticancer properties and has been used clinically in the treatment of a variety of cancers. It possesses significant toxicity, especially involving the bone marrow and gastrointestinal tract that has limited its use. Derivatives of 20-(S)-camptothecin have been made to increase the aqueous solubility of these compounds and/or modify the A-ring to increase membrane association. The 9-nitrocamptothecin (9-NC) derivative to be used in this study is insoluble in water, but has demonstrated potent antitumor effects in mice and antitumor effect in humans. However, the therapeutic index is low. In order to increase the therapeutic index, a liposomal formulation has been developed, which can be administered as an aerosol. In humans, dose of 0.52 mg/m2/day 5 days per weeks for eight 8 weeks of a 10 week course were well tolerated in the Phase I study. Partial responses were noted in patients with endometrial cancers. The recommended starting dose of L9NC in the Phase II study is 0.52 mg/m2/day to be administered once a day by aerosol (mouth-only breathing) for five consecutive days per week x 8 weeks followed by a 2 week rest. Courses are 10 weeks. This dose corresponds to approximately 1/6 of the MTD of oral 9-NC administered to untreated cancer patients.

Conditions

Corpus Uteri; Endometrial Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

9-NC in aerosol reservoir

Dose: 0.4 mg/ml of 9-NC in aerosol reservoir for 60 minutes (= daily dose of 0.52 mg/m2/day) per day X5 every week, X8 weeks, then observe for 2 weeks. One course = 10 weeks (45-47).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• All patients, 18 years of age or older, with metastatic and/or recurrent endometrial cancer or with mixed mesenchymal malignant tumors whose epithelial component is recurring, who have failed standard chemotherapy or hormonal regimens for their disease or who refuse recommended standard chemotherapy are eligible.
• Patients must have a life expectancy of at least 12 weeks.
• Patients must have a Zubrod performance status of 0-2.
• Patients must sign an informed consent.
• Patients should have adequate bone marrow function defined by an absolute peripheral granulocyte count of >1,500 cells/mm3 and platelet count >100,000/mm3 and absence of a regular red blood cell transfusion requirement.
• Patients should have adequate hepatic function with a total bilirubin < 2 mg/dl and SGOT or SGPT < two times the upper limit of normal, and adequate renal function as defined by a serum creatinine < 1.5 x upper limit of normal.
• Patients must not have a known symptomatic respiratory disease other than cancer, and must have a pulmonary function test equal to >50% forced expiratory volume in 1 second (FEV1), >50% FEV1/forced vital capacity (FVC), >50% total lung capacity (TLC), and >50% diffusing capacity of the lung for carbon monoxide (DLCO) of predicted values.

Exclusion Criteria

• Patients with symptomatic brain metastases are excluded from this study.
• Pregnant women or nursing mothers are not eligible for this trial. Patients of child bearing potential must use adequate contraception.
• Patients may receive no other concurrent chemotherapy or radiation therapy during this trial.
• Patients with severe medical problems such as uncontrolled diabetes mellitus or cardiovascular disease or active infections are not eligible for this trial.
• Any criteria that is borderline and may lead to ineligibility will be reviewed by the principal investigator (PI), who may override the eligibility criteria, after receiving sponsor agreement, if entry into the study is deemed to potentially benefit the patient.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Baylor College of Medicine

OTHER

Sponsor Role: collaborator

University of New Mexico

OTHER

Sponsor Role: lead

Responsible Party

University of New Mexico

Principal Investigators

Claire Verschraegen, MD

Role: PRINCIPAL_INVESTIGATOR

University of New Mexico

Locations

University of New Mexico

Albuquerque, New Mexico, United States

Countries

United States

Other Identifiers

1102C

Identifier Type: -

Identifier Source: org_study_id