Intrathecal Radioimmunotherapy, Radiation Therapy, and Chemotherapy After Surgery in Treating Patients With Medulloblastoma

• Sponsor: Memorial Sloan Kettering Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00058370
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 6
• Locations: 2
• Arm: 1
• Actual Duration (Months): 195.9
• Patients Per Site: 3
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Radioimmunotherapy uses radiolabeled monoclonal antibodies to locate tumor cells and deliver radioactive tumor-killing substances to them without harming normal cells. Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining intrathecal radioimmunotherapy and radiation therapy with combination chemotherapy may kill any tumor cells remaining after surgery.

PURPOSE: Phase II trial to study the effectiveness of combining intrathecal radioimmunotherapy and radiation therapy with combination chemotherapy in treating patients who have undergone surgery for medulloblastoma.

Condition or Disease	Intervention/Treatment	Phase
Brain and Central Nervous System Tumors	Drug: cisplatin; Drug: lomustine; Drug: vincristine sulfate; Procedure: adjuvant therapy; Radiation: iodine I 131 monoclonal antibody 3F8; Radiation: radiation therapy	N/A

Detailed Description

OBJECTIVES:

• Determine the feasibility of combining post-operative intrathecal radioimmunotherapy, craniospinal radiotherapy with intensity-modulated radiotherapy boost, and chemotherapy in patients with standard-risk medulloblastoma.

• Determine whether this regimen can maintain or exceed the current progression-free survival rate while decreasing long-term serious morbidity in these patients.

• Determine the long-term morbidities, most specifically neuropsychological, neuroendocrine, audiometric, and growth outcomes, in patients treated with this regimen.

OUTLINE:

• Radioimmunotherapy: Patients receive intrathecal iodine I 131 monoclonal antibody 3F8 on days 1 and 8.

• Radiotherapy: Beginning as soon as possible after radioimmunotherapy, patients undergo external-beam and intensity-modulated radiotherapy 5 days a week for 6 weeks.

• Chemotherapy: Patients receive vincristine IV once weekly for 8 weeks concurrently with radiotherapy. Beginning about 6 weeks after completion of radiotherapy (4 weeks after vincristine), patients receive cisplatin IV over 6 hours and oral lomustine on day 0 and vincristine IV on days 0, 7, and 14. Treatment repeats every 6 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 6-20 patients will be accrued for this study within 3.2 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Trial Of Radioimmunotherapy, Reduced-Dose External Beam Craniospinal Radiation Therapy With IMRT Boost, And Chemotherapy For Patients With Standard-Risk Medulloblastoma
• Actual Study Start Date: Feb 1, 2003
• Actual Primary Completion Date: Jun 1, 2019
• Actual Study Completion Date: Jun 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: histologic proof of medulloblastoma This is a single-arm study of post-operative radioimmunotherapy (intrathecal 131-I-3F8), reduced-dose craniospinal radiation therapy (1800 cGy), primary site boost (to 5400 cGy) via IMRT and standard chemotherapy.	Drug: cisplatin; Drug: lomustine; Drug: vincristine sulfate; Procedure: adjuvant therapy; Radiation: iodine I 131 monoclonal antibody 3F8; Radiation: radiation therapy

Outcome Measures

Primary Outcome Measures

1. Feasibility [2 years]

2. Progression-free Survival [2 years]

3. Morbidity [2 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 3 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

INCLUSION CRITERIA:

• Patients must have histologic proof of medulloblastoma reviewed by the Department of Pathology at the Memorial Sloan-Kettering Cancer Center.

• Patients must begin study prescribed therapy within 42 days of neurosurgical resection of the tumor

• Age ≥ 3-years-old. Post-operative head MRI must confirm ≤ 1.5 cm2 of residual tumor is present.

• Head and spine MRI and lumbar CSF cytology must not show any definitive evidence of leptomeningeal dissemination (Chang stage M-0).

• Examinations evaluating extra-neural sites will not be mandated, but any performed for clinical indications must be free of metastatic disease.

• No prior RT or chemotherapy for the medulloblastoma is permitted Patients must have adequate CSF flow (defined as lack of compartmentalization) on an 111-Indium DTPA flow study.

• Patients must have adequate organ function as defined by:

• Hepatic: total bilirubin < 2.0 mg/dl, AST < 3 x the upper limit of normal.

• Renal: Calculated creatinine clearance or nuclear GFR ≥ 70 ml/min/1.73 m^2.

• The patient, or for minors, a parent or legal guardian, must give informed written consent indicating they are aware of the investigational nature of this study.

EXCLUSION CRITERIA:

• Unable to start study prescribed therapy within 42 days of neurosurgical resection of the tumor

• Age less than 3 years > 1.5 cm2 residual tumor on post-operative head MRI

• Evidence of leptomeningeal dissemination on head or spine MRI or CSF cytology positivity

• Evidence of extra-neural metastases

• Prior radiation therapy or chemotherapy for the medulloblastoma

• Inadequate CSF flow on 111-Indium DTPA flow study Patients with signs or symptoms suggestive of increased intracranial pressure (headache, emesis, ocular paresis) will not be eligible until they are cleared by neurology and/or neurosurgery.

• Pregnancy

• Total bilirubin ≥ 2.0 mg/dl

• AST ≥ 3 x the upper limit of normal

• Creatinine clearance and GFR < 70 ml/min/1.73 m^2

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center	New York	New York	United States	10032
2	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065

Sponsors and Collaborators

• Memorial Sloan Kettering Cancer Center
• National Cancer Institute (NCI)

Investigators

• Study Chair: Ira Dunkel, MD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 26, 2008

More Information

Additional Information:

• Memorial Sloan Kettering Cancer Center

Publications

None provided.

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT00058370
• Other Study ID Numbers: 02-088; MSKCC-02088
• First Posted: Apr 9, 2003
• Last Update Posted: May 11, 2020
• Last Verified: Jun 1, 2019

• Keywords provided by Memorial Sloan Kettering Cancer Center: adult medulloblastoma; untreated childhood medulloblastoma
• Additional relevant MeSH terms: Nervous System Neoplasms; Central Nervous System Neoplasms; Medulloblastoma; Vincristine; Lomustine; Antibodies; Antibodies, Monoclonal

Study Results

Participant Flow

Arm/Group Title	Histologic Proof of Medulloblastoma
Arm/Group Description	This is a single-arm study of post-operative radioimmunotherapy (intrathecal 131-I-3F8), reduced-dose craniospinal radiation therapy (1800 cGy), primary site boost (to 5400 cGy) via IMRT and standard chemotherapy.
Period Title: Overall Study
STARTED	6
COMPLETED	6
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Histologic Proof of Medulloblastoma
Arm/Group Description	This is a single-arm study of post-operative radioimmunotherapy (intrathecal 131-I-3F8), reduced-dose craniospinal radiation therapy (1800 cGy), primary site boost (to 5400 cGy) via IMRT and standard chemotherapy.
Overall Participants	6
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	6
Sex: Female, Male (Count of Participants)
Female	3 50%
Male	3 50%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	6 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	6 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	6 100%

Outcome Measures

1. Primary Outcome

Title	Feasibility
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

No data were collected

Arm/Group Title	Histologic Proof of Medulloblastoma
Arm/Group Description	This is a single-arm study of post-operative radioimmunotherapy (intrathecal 131-I-3F8), reduced-dose craniospinal radiation therapy (1800 cGy), primary site boost (to 5400 cGy) via IMRT and standard chemotherapy.
Measure Participants	0

2. Primary Outcome

Title	Progression-free Survival
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Data were not collected

Arm/Group Title	Histologic Proof of Medulloblastoma
Arm/Group Description	This is a single-arm study of post-operative radioimmunotherapy (intrathecal 131-I-3F8), reduced-dose craniospinal radiation therapy (1800 cGy), primary site boost (to 5400 cGy) via IMRT and standard chemotherapy.
Measure Participants	0

3. Primary Outcome

Title	Morbidity
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Histologic Proof of Medulloblastoma
Arm/Group Description	This is a single-arm study of post-operative radioimmunotherapy (intrathecal 131-I-3F8), reduced-dose craniospinal radiation therapy (1800 cGy), primary site boost (to 5400 cGy) via IMRT and standard chemotherapy.
Measure Participants	6
Deceased	3 50%
Alive	3 50%

Adverse Events

Time Frame	1 year
Arm/Group Title	Histologic Proof of Medulloblastoma
Arm/Group Description	This is a single-arm study of post-operative radioimmunotherapy (intrathecal 131-I-3F8), reduced-dose craniospinal radiation therapy (1800 cGy), primary site boost (to 5400 cGy) via IMRT and standard chemotherapy.
All Cause Mortality
	Histologic Proof of Medulloblastoma
	Affected / at Risk (%)	# Events
Total	3/6 (50%)
Serious Adverse Events
	Histologic Proof of Medulloblastoma
	Affected / at Risk (%)	# Events
Total	2/6 (33.3%)
Gastrointestinal disorders
Constipation	1/6 (16.7%)
General disorders
Fever	1/6 (16.7%)
Infections and infestations
Infection w.out neutropenia	2/6 (33.3%)
Investigations
Leukocytes	1/6 (16.7%)
Lymphopenia	1/6 (16.7%)
Neutrophils/gran	1/6 (16.7%)
Other (Not Including Serious) Adverse Events
	Histologic Proof of Medulloblastoma
	Affected / at Risk (%)	# Events
Total	6/6 (100%)
Eye disorders
Ocular-Vision other	1/6 (16.7%)
Gastrointestinal disorders
Nausea	4/6 (66.7%)
Vomiting	3/6 (50%)
Stomatitis/pharyn	2/6 (33.3%)
Abdominal pain/cramping	1/6 (16.7%)
Constipation	1/6 (16.7%)
Diarrhea (Pts w/out col)	1/6 (16.7%)
Mucositis/Rad	1/6 (16.7%)
General disorders
Fatigue	3/6 (50%)
Fever	2/6 (33.3%)
Pain, other	2/6 (33.3%)
Immune system disorders
Allergic Reaction/Hyper	1/6 (16.7%)
Investigations
SGOT (AST)	1/6 (16.7%)
Weight loss	1/6 (16.7%)
Metabolism and nutrition disorders
Anorexia	2/6 (33.3%)
Dehydration	1/6 (16.7%)
Musculoskeletal and connective tissue disorders
Bone pain	2/6 (33.3%)
Nervous system disorders
Headache	2/6 (33.3%)
Ataxia	1/6 (16.7%)
Neuropathy-motor	1/6 (16.7%)
Neuropathy-sensory	1/6 (16.7%)
Psychiatric disorders
Mood alteration-anxiety	1/6 (16.7%)
Respiratory, thoracic and mediastinal disorders
Cough	1/6 (16.7%)
Skin and subcutaneous tissue disorders
Alopecia	2/6 (33.3%)
Derm, skin other	1/6 (16.7%)
Dry skin	1/6 (16.7%)
Rash, desquamation	1/6 (16.7%)
Sweating	1/6 (16.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.