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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00249990
Recruitment Status : Completed
First Posted : November 7, 2005
Last Update Posted : January 7, 2010
Baylor College of Medicine
Information provided by:
University of New Mexico

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.

Condition or disease Intervention/treatment Phase
Corpus Uteri Endometrial Cancer Drug: 9-NC in aerosol reservoir Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 39 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Aerosolized Liposomal 9-Nitro-20 (S)- Camptothecin (L9NC) in Patients With Metastatic or Recurrent Cancer of the Endometrium
Study Start Date : April 2003
Actual Primary Completion Date : July 2006
Actual Study Completion Date : September 2007

Intervention Details:
    Drug: 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).

Primary Outcome Measures :
  1. Overall response rate (complete and partial responses).Activity will be calculated as the proportion of pts with responsive disease & the 95% confidence interval for response. [ Time Frame: 4 years ]

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00249990

United States, New Mexico
University of New Mexico
Albuquerque, New Mexico, United States, 87131
Sponsors and Collaborators
University of New Mexico
Baylor College of Medicine
Principal Investigator: Claire Verschraegen, MD University of New Mexico

Responsible Party: Claire Verschraegen, MD; Principal Investigator, University of New Mexico Identifier: NCT00249990     History of Changes
Other Study ID Numbers: 1102C
First Posted: November 7, 2005    Key Record Dates
Last Update Posted: January 7, 2010
Last Verified: October 2008

Keywords provided by University of New Mexico:
Recurrent disease

Additional relevant MeSH terms:
Endometrial Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Uterine Diseases
Genital Diseases, Female
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action