Aerosol L9-NC and Temozolomide in Ewing's Sarcoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00492141
First received: June 26, 2007
Last updated: August 1, 2012
Last verified: August 2012
  Purpose

Primary Objectives:

  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. To determine the effectiveness of L9-NC given by aerosol in combination with temozolomide in patients with solid tumors involving the lungs.

Condition Intervention Phase
Ewing's Sarcoma
Drug: Temozolomide
Drug: L9-NC
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Aerosol Liposomal 9-Nitro-20(S)-Camptothecin (L9-NC) and Temozolomide in Ewing's Sarcoma and Other Solid Tumors With Lung Involvement

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Toxicity Profile [ Time Frame: From baseline to end study period (3 years) ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Number of Participants with Response According to Response Evaluation Criteria In Solid Tumors (RECIST) [ Time Frame: Baseline till after three cycles of therapy (approximately 9 weeks) ] [ Designated as safety issue: No ]
    Response by tumor measurements (centimeters) using RECIST criteria: Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): >30% decrease in sum of longest diameter (LD) of target lesions, reference baseline sum LD; Progressive Disease (PD): >20% increase in sum of LD of target lesions, reference smallest sum LD recorded since treatment started or appearance of one or > new lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, reference smallest sum LD since treatment started.


Enrollment: 10
Study Start Date: June 2006
Study Completion Date: September 2009
Primary Completion Date: May 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: L9-NC + Temozolomide
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
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.
Other Name: Temodar
Drug: L9-NC

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.

Other Names:
  • 9-Nitro-20(S)-Camptothecin
  • Aerosol L9-NC

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   10 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00492141

Locations
United States, Texas
U.T.M.D. Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Cynthia E. Herzog, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00492141     History of Changes
Other Study ID Numbers: 2005-0889
Study First Received: June 26, 2007
Last Updated: August 1, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Ewing's Sarcoma
Lung Involvement
Temozolomide
Temodar
Aerosol Liposomal 9-Nitro-20(S)-Camptothecin
Aerosol L9-NC
L9-NC

Additional relevant MeSH terms:
Sarcoma, Ewing's
Sarcoma
Osteosarcoma
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Camptothecin
Temozolomide
9-nitrocamptothecin
Dacarbazine
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Phytogenic
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on July 22, 2014