Phase II Study of Aerosolized Liposomal 9-Nitro-20 (S)- Camptothecin (L9NC) in Patients With Metastatic or Recurrent Cancer of the Endometrium
18 Years
N/A
Female
Corpus Uteri, Endometrial Cancer
Trial Information
Phase II Study of Aerosolized Liposomal 9-Nitro-20 (S)- Camptothecin (L9NC) in Patients With Metastatic or Recurrent Cancer of the Endometrium
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.
Inclusion 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.
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
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.
Outcome Time Frame:
4 years
Safety Issue:
Yes
Principal Investigator
Claire Verschraegen, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
University of New Mexico
Authority:
United States: Institutional Review Board
Study ID:
1102C
NCT ID:
NCT00249990
Start Date:
April 2003
Completion Date:
September 2007
Related Keywords:
- Corpus Uteri
- Endometrial Cancer
- Uterus
- Recurrent disease
- Treatment
- 9-Nitrocamptothecin
- Endometrium
- Endometrial Neoplasms
- Adenoma
Name | Location |
|---|---|
| University of New Mexico | Albuquerque, New Mexico 87131 |
