Clinical Trials Logo

Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT00983398
Other study ID # IRB00005056
Secondary ID NCI-2013-00790OH
Status Active, not recruiting
Phase Phase 1/Phase 2
First received
Last updated
Start date July 9, 2009
Est. completion date December 31, 2022

Study information

Verified date October 2021
Source OHSU Knight Cancer Institute
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This phase I/II trial studies the side effects and best dose of melphalan when given together with carboplatin, mannitol, and sodium thiosulfate, and to see how well they work in treating patients with central nervous system (CNS) embryonal or germ cell tumors that is growing, spreading, or getting worse (progressive) or has come back (recurrent). Drugs used in chemotherapy, such as melphalan and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Osmotic blood-brain barrier disruption (BBBD) uses mannitol to open the blood vessels around the brain and allow cancer-killing substances to be carried directly to the brain. Sodium thiosulfate may help lessen or prevent hearing loss and toxicities in patients undergoing chemotherapy with carboplatin and BBBD. Giving melphalan together with carboplatin, mannitol, and sodium thiosulfate may be an effective treatment for recurrent or progressive CNS embryonal or germ cell tumors.


Description:

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) of intra-arterial (IA) melphalan given with IA carboplatin, osmotic BBBD and delayed intravenous (IV) sodium thiosulfate (STS) in subjects with recurrent or progressive embryonal and germ cell tumors of the CNS. (Phase I) II. To estimate the response rate in subjects with recurrent or progressive CNS embryonal and germ cell tumors treated with IA carboplatin, IA melphalan, osmotic BBBD and delayed IV STS. (Phase II) SECONDARY OBJECTIVES: I. To describe 2-year progression-free survival (PFS) and overall survival (OS) rates in subjects with recurrent or progressive CNS embryonal and germ cell tumors treated with IA carboplatin, IA melphalan, osmotic BBBD and delayed IV STS. (Phase II) II. To describe neuropsychological and audiology outcomes in subjects with recurrent or progressive CNS embryonal and germ cell tumors treated with IA carboplatin, IA melphalan, osmotic BBBD and delayed IV STS. (Phase II) III. To describe the overall toxicity of IA carboplatin and IA melphalan in conjunction with osmotic BBBD and delayed STS chemoprotection in subjects with recurrent or progressive CNS embryonal or germ cell tumors. (Phase II) OUTLINE: This is a phase I, dose-escalation study of melphalan followed by a phase II study. Patients receive mannitol IA over 30 seconds, melphalan IA over 10 minutes, and carboplatin IA over 10 minutes. Patients then receive sodium thiosulfate IV over 15 minutes at 4 and 8 hours after carboplatin. Treatment repeats every 4-6 weeks for up to 12 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 1 year, every 6 months for 1 year, and then annually for 3 years.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 17
Est. completion date December 31, 2022
Est. primary completion date December 31, 2021
Accepts healthy volunteers No
Gender All
Age group 18 Years to 45 Years
Eligibility Inclusion Criteria: - Subjects with histologically confirmed CNS embryonal tumor (primitive neuroectodermal tumor [PNET], medulloblastoma, atypical teratoid rhabdoid tumor [ATRT], medulloepithelioma, pineoblastoma or ependymoblastoma), or germ cell tumor, are eligible; subjects may be enrolled on study as first-line treatment; diagnosis will be made on the basis of computed tomography (CT)-assisted or stereotactic biopsy, open biopsy, surgical resection, cerebrospinal fluid (CSF) cytology, or elevated tumor markers - Subjects may be enrolled as part of first-line treatment; those subjects who enroll as first-line treatment will not be restricted from traditional treatments in the future; at least 14 days must have elapsed since completion of cranial radiotherapy and 28 days since completion of chemotherapy; at least 28 days must have elapsed since completion of total spine radiotherapy - Subjects with no previous radiotherapy treatment must have a consultation with a radiation oncologist or providers must have a discussion in the context of Neuro-Oncology Tumor Board within 60 days prior to start of IA/BBBD chemotherapy to determine the need for radiotherapy prior to or after IA/BBBD - Glomerular filtration rate (GFR) or creatinine clearance (CrCl) (24 hour urine) greater than 30 ml/min corrected for body surface area - Absolute granulocyte count >= 1.0 x 10^3/mm^3 - Platelets >= 100 x 10^3/mm^3 - Creatinine < 1.5 - Total bilirubin < 2.0 mg/dl - Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 2.5 x upper limits of normal - Subject's Karnofsky performance status (KPS) must be >= 50% (Eastern Cooperative Oncology Group [ECOG] performance score < 3) - Subjects or their legal guardian must sign a written informed consent in accordance with institutional guidelines - Sexually active women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study treatment and for the duration of study treatment; should a female become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately - For the phase II portion of the study, subjects must have disease that is evaluable for response; subjects who have had radiation to all sites of disease are not eligible unless there is imaging evidence of active tumor, ie: increased blood volume Exclusion Criteria: - Subjects with radiographic signs of excessive intracranial mass effect with associated rapid neurologic deterioration and/or spinal cord block - Subjects at significant risk with general anesthesia - Subjects with uncontrolled (over the last 30 days) clinically significant confounding medical conditions - Subject is pregnant or is lactating - Subjects who have contraindications to carboplatin, melphalan, or STS

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Carboplatin
Given IA
Mannitol
Given IA
Melphalan
Given IA
Other:
Quality-of-Life Assessment
Ancillary studies
Questionnaire Administration
Ancillary studies
Drug:
Sodium Thiosulfate
Given IV

Locations

Country Name City State
United States University of Minnesota/Masonic Cancer Center Minneapolis Minnesota
United States OHSU Knight Cancer Institute Portland Oregon

Sponsors (3)

Lead Sponsor Collaborator
OHSU Knight Cancer Institute National Institute of Neurological Disorders and Stroke (NINDS), Oregon Health and Science University

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Maximum tolerated dose (Phase I) Will be assessed based on the incidence of dose-limiting toxicity, graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. All toxicities will be tabulated by event and by overall. The toxicities will also be tabulated by highest grade. The recovery from toxicities (i.e. hematologic toxicities) will also be summarized. 6 weeks
Primary Response rate (Phase II) Descriptive statistics will be estimated. Up to 5 years
Secondary Progression free survival rate (Phase II) Estimation made using Kaplan-Meier product limit estimation. A Cox proportional hazards regression model will be fit to the data to estimate the association of progression free survival and overall survival with baseline demographic and disease characteristics. Time from first study treatment to evidence of first progression, assessed at 2 years
Secondary Overall survival rate (Phase II) Estimation made using Kaplan-Meier product limit estimation. A Cox proportional hazards regression model will be fit to the data to estimate the association of progression free survival and overall survival with baseline demographic and disease characteristics. Time from time of first study treatment until death, assessed at 2 years
Secondary Change in neurocognitive assessment scores (Phase II) Quantitative scores, whenever possible, will be derived from each measure and converted to measure-specific Z scores using normative data. Post-treatment Z scores will be subtracted from pre-treatment Z scores to calculate absolute change in neuropsychological test performance. Significant change will be defined as change of 1 standard deviation. These data will be summarized descriptively. Baseline to 90 days after completion of study treatment
Secondary Proportion of patients with ototoxicity (Phase II) Will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Estimated using proportions with associated confidence intervals. Up to 30 days after completion of study treatment
See also
  Status Clinical Trial Phase
Active, not recruiting NCT01326104 - Vaccine Immunotherapy for Recurrent Medulloblastoma and Primitive Neuroectodermal Tumor Phase 2
Recruiting NCT04081701 - 68-Ga DOTATATE PET/MRI in the Diagnosis and Management of Somatostatin Receptor Positive CNS Tumors. Phase 4
Completed NCT03273712 - Dosimetry-Guided, Peptide Receptor Radiotherapy (PRRT) With 90Y-DOTA- tyr3-Octreotide (90Y-DOTATOC) Phase 2
Completed NCT00994071 - A Phase I Study of ABT-888, an Oral Inhibitor of Poly(ADP-ribose) Polymerase and Temozolomide in Children With Recurrent/Refractory CNS Tumors Phase 1
Active, not recruiting NCT02875314 - HeadStart4: Newly Diagnosed Children (<10 y/o) With Medulloblastoma and Other CNS Embryonal Tumors Phase 4
Completed NCT02441062 - Impact of Ga-68 DOTATOC PET-CT Imaging in Management of Neuroendocrine Tumors Phase 2
Completed NCT01171469 - Vaccination With Dendritic Cells Loaded With Brain Tumor Stem Cells for Progressive Malignant Brain Tumor Phase 1
Completed NCT00520936 - A Study of Pemetrexed in Children With Recurrent Cancer Phase 2
Completed NCT03257631 - A Study of Pomalidomide Monotherapy for Children and Young Adults With Recurrent or Progressive Primary Brain Tumors Phase 2
Recruiting NCT04541082 - Phase I Study of Oral ONC206 in Recurrent and Rare Primary Central Nervous System Neoplasms Phase 1
Recruiting NCT04337177 - Flavored, Oral Irinotecan VAL-413 (Orotecan®) Given With Temozolomide for Treatment of Recurrent Pediatric Solid Tumors Phase 1
Completed NCT02502708 - Study of the IDO Pathway Inhibitor, Indoximod, and Temozolomide for Pediatric Patients With Progressive Primary Malignant Brain Tumors Phase 1
Completed NCT01208831 - An East Asian Study of LDE225 Phase 1
Completed NCT01505569 - Auto Transplant for High Risk or Relapsed Solid or CNS Tumors N/A
Recruiting NCT04049669 - Pediatric Trial of Indoximod With Chemotherapy and Radiation for Relapsed Brain Tumors or Newly Diagnosed DIPG Phase 2
Recruiting NCT05125666 - Efficacy of Dual Task Training on Children With Ataxia After Medulloblastoma Resection Phase 2
Completed NCT03043391 - Phase 1b Study PVSRIPO for Recurrent Malignant Glioma in Children Phase 1
Recruiting NCT05278208 - Lutathera for Treatment of Recurrent or Progressive High-Grade CNS Tumors Phase 1/Phase 2
Active, not recruiting NCT02724579 - Reduced Craniospinal Radiation Therapy and Chemotherapy in Treating Younger Patients With Newly Diagnosed WNT-Driven Medulloblastoma Phase 2
Recruiting NCT04402073 - Personalized Risk-Adapted Therapy in Post-Pubertal Patients With Newly-Diagnosed Medulloblastoma Phase 2