Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00119301
Other study ID # 05-028
Secondary ID MSKCC-IRB-05028
Status Completed
Phase Phase 1
First received July 12, 2005
Last updated January 15, 2013
Start date April 2005

Study information

Verified date January 2013
Source Memorial Sloan Kettering Cancer Center
Contact n/a
Is FDA regulated No
Health authority United States: Federal Government
Study type Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as methotrexate, trimetrexate glucuronate, and leucovorin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of trimetrexate glucuronate when given together with methotrexate and leucovorin in treating patients with refractory or recurrent osteosarcoma.


Description:

OBJECTIVES:

Primary

- Determine the maximum tolerated dose of trimetrexate glucuronate when administered with high-dose methotrexate and leucovorin calcium in patients with refractory or recurrent high-grade osteosarcoma.

Secondary

- Determine the dose-limiting toxic effects of this regimen in these patients.

- Determine, preliminarily, the antitumor activity of this regimen in these patients.

OUTLINE: This is a dose-escalation study of trimetrexate glucuronate.

Patients receive high-dose methotrexate IV over 4 hours on days 1 and 8 and oral trimetrexate glucuronate twice daily on days 2-6 and 9-13. Patients also receive leucovorin calcium IV continuously over 24 hours or orally 2 or 4 times daily on days 9-14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of trimetrexate glucuronate until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: A maximum of 18 patients will be accrued for this study within 2 years.


Recruitment information / eligibility

Status Completed
Enrollment 18
Est. completion date
Est. primary completion date April 2007
Accepts healthy volunteers No
Gender Both
Age group 1 Year to 35 Years
Eligibility DISEASE CHARACTERISTICS:

- Histologically confirmed malignant osteosarcoma

- High-grade disease

- Recurrent or refractory disease after prior standard chemotherapy comprising methotrexate, doxorubicin, cisplatin, and ifosfamide

- No low-grade osteosarcoma

- No parosteal or periosteal sarcoma

- No osteosarcoma arising in premalignant bony lesions (e.g., Paget's disease) OR in a prior radiotherapy field

- No symptomatic or known brain or leptomeningeal involvement

PATIENT CHARACTERISTICS:

Age

- 1 to 35

Performance status

- Karnofsky 70-100% (for patients > 16 years of age)

- Lansky 70-100% (for patients = 16 years of age)

Life expectancy

- At least 3 months

Hematopoietic

- Absolute neutrophil count = 1,000/mm^3

- Platelet count = 75,000/mm^3

Hepatic

- Bilirubin = 1.5 times normal

- AST and ALT = 5 times normal

- Albumin = 2 g/dL

- No clinically significant liver disease

Renal

- Creatinine = 1.5 times normal OR

- Creatinine clearance or radioisotope glomerular filtration rate = lower limit of normal

Cardiovascular

- Shortening fraction = 27% by echocardiogram OR

- Ejection fraction = 50% by gated radionuclide study

- No congestive heart failure

- No angina pectoris

- No myocardial infarction within the past year

- No uncontrolled arterial hypertension

- No uncontrolled arrhythmias

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No history of significant neurological or psychiatric disorder

- No active infection

- No symptomatic peripheral neuropathy = grade 2

- No other serious illness or medical condition

PRIOR CONCURRENT THERAPY:

Biologic therapy

- At least 7 days since prior biologic therapy

- At least 6 months since prior allogeneic stem cell transplantation AND no evidence of active graft-versus-host disease

- No concurrent sargramostim (GM-CSF)

Chemotherapy

- See Disease Characteristics

- More than 2 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosoureas)

Endocrine therapy

- Not specified

Radiotherapy

- See Disease Characteristics

- At least 2 weeks since prior local palliative radiotherapy (small port)

- At least 6 months since prior craniospinal radiotherapy

- At least 6 months since prior radiotherapy to = 50% of the pelvis

- At least 6 weeks since prior substantial radiotherapy to the bone marrow

Surgery

- Not specified

Other

- Recovered from prior therapy

- More than 30 days since prior and no other concurrent investigational drugs

- More than 30 days since prior and no concurrent participation in another clinical trial

- No concurrent medications that may interact with study drugs

Study Design

Primary Purpose: Treatment


Related Conditions & MeSH terms


Intervention

Drug:
leucovorin calcium

methotrexate

trimetrexate glucuronate


Locations

Country Name City State
United States Memorial Sloan-Kettering Cancer Center New York New York

Sponsors (2)

Lead Sponsor Collaborator
Memorial Sloan Kettering Cancer Center National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Maximum tolerated dose (MTD) after 1 course of treatment Yes
Primary Dose-limiting toxicities as assessed by hematology and biochemistry testing on days 1, 8, and 28 of each course Yes
Secondary Antitumor activity as measured by radiographic response using RECIST criteria after every 2 courses of treatment No
Secondary Antitumor activity as measured by pathologic response using the Huvos grading system to evaluate post-treatment tumor necrosis at time of tumor resection after completion of study treatment No
See also
  Status Clinical Trial Phase
Recruiting NCT04986748 - Using QPOP to Predict Treatment for Sarcomas and Melanomas
Recruiting NCT04457258 - 68Ga-FAPi-46 PET/CT Scan in Imaging Patients With Sarcoma Early Phase 1
Completed NCT04474678 - Quality Improvement Project - "My Logbook! - I Know my Way Around!"; ("Mein Logbuch - Ich Kenne Mich Aus!") N/A
Recruiting NCT05415098 - Study of Safety, Pharmacokinetic and Efficacy of APG-5918 in Advanced Solid Tumors or Lymphomas Phase 1
Recruiting NCT04535713 - GALLANT: Metronomic Gemcitabine, Doxorubicin, Docetaxel and Nivolumab for Advanced Sarcoma Phase 2
Completed NCT03521531 - Burden and Medical Care of Sarcoma in Germany
Completed NCT02496520 - Dendritic Cell-based Immunotherapy for Advanced Solid Tumours of Children and Young Adults Phase 1/Phase 2
Terminated NCT02054104 - Adjuvant Tumor Lysate Vaccine and Iscomatrix With or Without Metronomic Oral Cyclophosphamide and Celecoxib in Patients With Malignancies Involving Lungs, Esophagus, Pleura, or Mediastinum Phase 1/Phase 2
Terminated NCT00788125 - Dasatinib, Ifosfamide, Carboplatin, and Etoposide in Treating Young Patients With Metastatic or Recurrent Malignant Solid Tumors Phase 1/Phase 2
Active, not recruiting NCT04383210 - Study of Seribantumab in Adult Patients With NRG1 Gene Fusion Positive Advanced Solid Tumors Phase 2
Active, not recruiting NCT04577014 - Retifanlimab (Anti-PD-1 Antibody) With Gemcitabine and Docetaxel in Patients With Advanced Soft Tissue Sarcoma Phase 1/Phase 2
Completed NCT04052334 - Lymphodepletion Plus Adoptive Cell Therapy With High Dose IL-2 in Adolescent and Young Adult Patients With Soft Tissue Sarcoma Phase 1
Completed NCT01593748 - A Phase II Trial Comparing Gemcitabine and Pazopanib Versus Gemcitabine and Docetaxel for Patients With Advanced Soft Tissue Sarcoma Phase 2
Completed NCT00199849 - NY-ESO-1 Plasmid DNA (pPJV7611) Cancer Vaccine Phase 1
Recruiting NCT04367779 - Research of Biomarkers of Response to Proton Beam Therapy in Pediatric and Adult Patients.
Completed NCT01879085 - Study of Vorinostat in Combination With Gemcitabine and Docetaxel in Advanced Sarcoma Phase 1/Phase 2
Recruiting NCT04553692 - Phase 1a/1b Study of Aplitabart (IGM-8444) Alone or in Combination in Participants With Relapsed, Refractory, or Newly Diagnosed Cancers Phase 1
Completed NCT01209598 - PD0332991 (Palbociclib) in Patients With Advanced or Metastatic Liposarcoma Phase 2
Completed NCT04553471 - Palliative Lattice Stereotactic Body Radiotherapy (SBRT) for Patients With Sarcoma, Thoracic, Abdominal, and Pelvic Cancers N/A
Withdrawn NCT04906876 - A Phase 2 Study of 9-ING-41Combined With Chemotherapy in Adolescents and Adults With Advanced Sarcomas Phase 2