Aerosol L9-NC and Temozolomide in Ewing's Sarcoma

NCT00492141 | Completed Phase 1 DMC

• 1 other identifier: 2005-0889
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Primary Objectives:

1. 1.To determine the feasibility and toxicity profile of administering liposomal 9-Nitro-20-(S)-Camptothecin (L9-NC) by aerosol alone and in combination with temozolomide.
2. 2.To determine the effectiveness of L9-NC given by aerosol in combination with temozolomide in patients with solid tumors involving the lungs.

Conditions

Ewing's Sarcoma

Keywords

Ewing's Sarcoma; Lung Involvement; Temozolomide; Temodar; Aerosol Liposomal 9-Nitro-20(S)-Camptothecin; Aerosol L9-NC; L9-NC

Outcome Measures

Primary Outcomes (1)

• Toxicity Profile

  Toxicity profile of administering liposomal 9-Nitro-20-(S)-Camptothecin (L9-NC) by aerosol alone and in combination with temozolomide. All toxicities evaluated according to NCI Common Toxicity Criteria, Version 3.0 and recorded prior to each cycle of therapy.

  From baseline to end study period (3 years)

Secondary Outcomes (1)

• Number of Participants with Response According to Response Evaluation Criteria In Solid Tumors (RECIST)

  Baseline till after three cycles of therapy (approximately 9 weeks)

Study Arms (1)

L9-NC + Temozolomide

EXPERIMENTAL

Liposomal 9-nitro-20(S)-camptothecin (L9-NC) alone, total 10 ml of 0.4 mg/ml in aerosol reservoir once a day for 5 days in row each 2 weeks, followed by 2 weeks off; then in combination with Temozolomide 100 mg/m\^2 oral/day for Cycle 2 Days 1-5.

Drug: Temozolomide; Drug: L9-NC

Interventions

Temozolomide DRUG

Cycle 2, Dose Level 1 = 100 mg/m\^2 by mouth (PO) Daily, Days 1-5 Prior to L9-NC; Cycle 3, Dose Level 2 = If the patient has no toxicity greater than grade 2, advance to 100 mg/m\^2 PO Every 12 Hours, Days 1-5 Prior to L9-NC. If the patient is not able to advance to dose level 2, the patient may continue at dose level 1 as in cycle 2; Cycle 4 and beyond = Patients will continue on dose level 1 or 2 as given in cycle 3.

Also known as: Temodar

L9-NC + Temozolomide

L9-NC DRUG

Cycle 1 = Administered by aerosol 5 consecutive days per week for 2 weeks. A total of 10 ml of 0.4 mg/ml in an aerosol reservoir delivered over approximately 30 minutes per day given once a day, 5 days a week, for 2 weeks, followed by 2 weeks off. Cycle 2, Dose Level 1 = Week 1, doses 1-5 preceded by temozolomide. Continue L9-NC once a day, 5 days a week, for 2 weeks, followed by 2 weeks off. Cycle 3, Dose Level 2 = If the patient has no toxicity greater than grade 2, due to drug, during cycle 2, L9-NC may be increased to twice daily, approximately 12 hours apart. Week 1, the morning dose on days 1-5 preceded by temozolomide. L9-NC will be given twice a day, 5 days a week, for 2 weeks, followed by 2 weeks off. If the patient is not able to advance to dose level 2, the patient may continue at dose level 1 as in cycle 2. Cycle 4 and beyond, patients will continue on dose level 1 or 2 as given in cycle 3.

Also known as: 9-Nitro-20(S)-Camptothecin, Aerosol L9-NC

L9-NC + Temozolomide

Eligibility Criteria

• Age: 10 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients, 10 years of age or older, with primary or metastatic cancer in the lungs, who have failed or progressed on front line therapy and have no standard therapies available for treatment are eligible. Patients may also have disease in other sites, but must have current lung involvement to be eligible.
• Patients should have adequate bone marrow function, defined by: absolute peripheral granulocyte count of \>/= 1500 cells/mm\^3, platelet count \> 100,000 platelets/mm\^3, and Hgb \> 8.0 g/dl. For patients with documented bone marrow involvement, the following counts are acceptable for enrollment: absolute peripheral granulocyte count of \> 1000 cells/mm\^3 , platelet count \> 75,000 platelets/mm\^3.
• Patients should have adequate hepatic function, defined by: total bilirubin \< 2 mg/dl and ALT or AST \< 2x upper limit of normal.
• Patients should have adequate renal function, defined by serum creatinine \</= 2 mg/dl.
• Patients must have adequate pulmonary function, as defined by a pulmonary function test with: \>/= 50% FVC, \>/= 50% FEV1 and \>/= 50% DLCO of predicted values

You may not qualify if:

• Patients with symptomatic brain metastases.
• Pregnant women or nursing mothers. Patients of child bearing potential must use adequate contraception.
• Patients receiving concurrent chemotherapy.
• Patients may not receive concurrent radiation therapy to the chest during cycles 1-3. Radiation therapy to disease in other areas of the body is permissible at any time, but such lesions will not be evaluable for response. Although patients who have received prior radiation to the chest are eligible, patients should be at least 4 weeks from prior radiation to the chest. Any chest lesion treated with radiation must have progressed to be considered measurable for this study.
• Patients with severe medical problems such as uncontrolled diabetes mellitus (glucose consistently greater than 200 mg/dl, or Hemoglobin A1c greater than 8%) or symptomatic cardiovascular disease (New York class III) or active infections requiring IV antibiotics are not eligible for this trial.
• Patients requiring oxygen.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

U.T.M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• UT MD Anderson Cancer Center

MeSH Terms

Conditions

Sarcoma, Ewing

Interventions

Temozolomide; rubitecan

Condition Hierarchy (Ancestors)

Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Cynthia E. Herzog, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2007
• First Posted: June 27, 2007
• Study Start: June 1, 2006
• Primary Completion: May 1, 2007
• Study Completion: September 1, 2009
• Last Updated: August 2, 2012

Record last verified: 2012-08

Locations

US (1)