Arsenic Trioxide in Treating Patients With Advanced Neuroblastoma or Other Childhood Solid Tumors

• Sponsor: Memorial Sloan Kettering Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00024258
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 22
• Location: 1
• Arm: 1
• Duration (Months): 98
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase II trial to study the effectiveness of arsenic trioxide in treating children who have advanced neuroblastoma or other solid tumors.

Condition or Disease	Intervention/Treatment	Phase
Brain and Central Nervous System Tumors; Childhood Germ Cell Tumor; Extragonadal Germ Cell Tumor; Kidney Cancer; Liver Cancer; Neuroblastoma; Ovarian Cancer; Retinoblastoma; Sarcoma	Drug: arsenic trioxide	Phase 2

Detailed Description

OBJECTIVES:

• Determine the response rates of patients with advanced neuroblastoma or other pediatric solid tumors treated with arsenic trioxide.

• Determine the toxicity of this drug in these patients.

OUTLINE: Patients are stratified according to type of disease (neuroblastoma with progressive disease vs neuroblastoma with stable refractory disease vs other solid tumor).

Patients receive arsenic trioxide IV over 1-4 hours on days 1-5 and 8-12. Treatment repeats every 28 days for a maximum of 6 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 2-3 months for 1 year and then annually thereafter.

Study Design

• Study Type: Interventional
• Actual Enrollment: 22 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Arsenic Trioxide in Neuroblastoma and Other Pediatric Solid Tumors
• Study Start Date: Mar 1, 2001
• Actual Primary Completion Date: May 1, 2009
• Actual Study Completion Date: May 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arsenic Trioxide Patients receive arsenic trioxide IV over 1-4 hours on days 1-5 and 8-12. Treatment repeats every 28 days for a maximum of 6 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 2-3 months for 1 year and then annually thereafter.	Drug: arsenic trioxide

Outcome Measures

Primary Outcome Measures

1. Response Rate After Every 3 Courses During Treatment and Then Every 2-3 Months for 1 Year After Completion of Treatment [1 year]

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 40 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically confirmed neuroblastoma or other pediatric solid tumor (nonmyeloid and nonlymphoid) including the following:

• Ewing's family of tumors/primitive neuroectodermal tumor

• Retinoblastoma

• Nephroblastoma

• Osteosarcoma

• Rhabdomyosarcoma

• Desmoplastic small round-cell tumor

• Hepatoblastoma

• Germ cell tumors

• Medulloblastoma

• Relapsed from or resistant to prior standard anticancer therapy and/or no known standard therapy available

• Measurable disease (e.g., solid mass with definable dimensions) OR

• Evaluable disease (e.g., bone marrow involvement or malignant pleural effusion)

PATIENT CHARACTERISTICS:

Age:

• 40 and under

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Bilirubin no greater than 2.5 times upper limit of normal (ULN)

Renal:

• Creatinine no greater than 2.5 times ULN

Cardiovascular:

• Absolute QT interval no greater than 460 msec in the presence of adequate potassium and magnesium levels

Other:

• No pre-existing neurotoxicity/neuropathy grade 2 or greater

• No pre-existing convulsive disorder

• No active serious infections uncontrolled by antibiotics

• Negative pregnancy test

• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• More than 3 weeks since prior cytotoxic chemotherapy

• No other concurrent cytotoxic chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• Concurrent radiotherapy allowed provided measurable or evaluable disease exists outside radiation field

Surgery:

• Not specified

Other:

• No other concurrent investigational agents

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021

Sponsors and Collaborators

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

Investigators

• Study Chair: Brian H. Kushner, MD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT00024258
• Other Study ID Numbers: 01-042; P30CA008748; MSKCC-01042; CTI-1059; NCI-G01-2014
• First Posted: Jan 27, 2003
• Last Update Posted: Nov 25, 2015
• Last Verified: Oct 1, 2015

• Keywords provided by Memorial Sloan Kettering Cancer Center: metastatic osteosarcoma; recurrent childhood rhabdomyosarcoma; regional neuroblastoma; disseminated neuroblastoma; stage 4S neuroblastoma; recurrent neuroblastoma; stage III childhood liver cancer; stage IV childhood liver cancer; recurrent childhood liver cancer; childhood hepatoblastoma; stage III Wilms tumor; stage IV Wilms tumor; stage V Wilms tumor; recurrent Wilms tumor and other childhood kidney tumors; intraocular retinoblastoma; extraocular retinoblastoma; recurrent retinoblastoma; recurrent osteosarcoma; childhood germ cell tumor; metastatic childhood soft tissue sarcoma; recurrent childhood soft tissue sarcoma; localized unresectable neuroblastoma; previously untreated childhood rhabdomyosarcoma; childhood desmoplastic small round cell tumor; untreated childhood medulloblastoma; recurrent childhood medulloblastoma; previously treated childhood rhabdomyosarcoma; metastatic Ewing sarcoma/peripheral primitive neuroectodermal tumor; recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor; childhood teratoma; childhood malignant testicular germ cell tumor; childhood malignant ovarian germ cell tumor; childhood extragonadal germ cell tumor; recurrent childhood malignant germ cell tumor
• Additional relevant MeSH terms: Neoplasms; Sarcoma; Liver Neoplasms; Neuroblastoma; Neoplasms, Germ Cell and Embryonal; Nervous System Neoplasms; Central Nervous System Neoplasms; Retinoblastoma; Arsenic Trioxide

Study Results

Participant Flow

Arm/Group Title	Arsenic Trioxide
Arm/Group Description	Patients receive arsenic trioxide IV over 1-4 hours on days 1-5 and 8-12. Treatment repeats every 28 days for a maximum of 6 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 2-3 months for 1 year and then annually thereafter.
Period Title: Overall Study
STARTED	22
COMPLETED	13
NOT COMPLETED	9

Baseline Characteristics

Arm/Group Title	Arsenic Trioxide
Arm/Group Description	Patients receive arsenic trioxide IV over 1-4 hours on days 1-5 and 8-12. Treatment repeats every 28 days for a maximum of 6 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 2-3 months for 1 year and then annually thereafter.
Overall Participants	22
Age (Count of Participants)
<=18 years	19 86.4%
Between 18 and 65 years	3 13.6%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	6 27.3%
Male	16 72.7%
Region of Enrollment (participants) [Number]
United States	22 100%

Outcome Measures

1. Primary Outcome

Title	Response Rate After Every 3 Courses During Treatment and Then Every 2-3 Months for 1 Year After Completion of Treatment
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arsenic Trioxide
Arm/Group Description	Patients receive arsenic trioxide IV over 1-4 hours on days 1-5 and 8-12. Treatment repeats every 28 days for a maximum of 6 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 2-3 months for 1 year and then annually thereafter.
Measure Participants	21
Progression of Disease	16 72.7%
Stable Disease	5 22.7%

Adverse Events

Arm/Group Title	Arsenic Trioxide
Arm/Group Description	Patients receive arsenic trioxide IV over 1-4 hours on days 1-5 and 8-12. Treatment repeats every 28 days for a maximum of 6 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 2-3 months for 1 year and then annually thereafter.
All Cause Mortality
	Arsenic Trioxide
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Arsenic Trioxide
	Affected / at Risk (%)	# Events
Total	12/22 (54.5%)
Blood and lymphatic system disorders
Febrile Neutropenia	1/22 (4.5%)	1
Anemia	1/22 (4.5%)	1
Gastrointestinal disorders
Vomiting	1/22 (4.5%)	1
Infections and infestations
Catheter related infection	1/22 (4.5%)	1
Infection NOS	4/22 (18.2%)	4
Investigations
Alanine aminotransferase increased	1/22 (4.5%)	1
Aspartate aminotransferase increased	1/22 (4.5%)	1
Blood bilirubin increased	1/22 (4.5%)	1
Neutrophil count decrease	3/22 (13.6%)	4
Electrocardiogram QT corrected interval prolonged	1/22 (4.5%)	1
Metabolism and nutrition disorders
Dehydration	1/22 (4.5%)	1
Hypercalcemia	1/22 (4.5%)	1
Hyperkalemia	1/22 (4.5%)	1
Hypocalcemia	1/22 (4.5%)	1
Nervous system disorders
Neuralgia	1/22 (4.5%)	1
Renal and urinary disorders
Renal failure	1/22 (4.5%)	1
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders - Other, specify Respiratory disorder	2/22 (9.1%)	2
Other (Not Including Serious) Adverse Events
	Arsenic Trioxide
	Affected / at Risk (%)	# Events
Total	14/22 (63.6%)
Blood and lymphatic system disorders
Febrile Neutropenia	1/22 (4.5%)	1
Anemia	3/22 (13.6%)	3
Cardiac disorders
Sinus tachycardia	1/22 (4.5%)	1
Eye disorders
Conjunctivitis	1/22 (4.5%)	1
Dry Eye	1/22 (4.5%)	1
Gastrointestinal disorders
Constipation	3/22 (13.6%)	3
Gastrointestinal other	2/22 (9.1%)	2
Nausea	3/22 (13.6%)	3
Mucositis	1/22 (4.5%)	1
Vomiting	3/22 (13.6%)	4
General disorders
Edema	3/22 (13.6%)	3
Fatigue	1/22 (4.5%)	1
Fever	2/22 (9.1%)	2
Pain, other	3/22 (13.6%)	4
Infections and infestations
Infection w/o neutropenia	4/22 (18.2%)	4
Injury, poisoning and procedural complications
Bruising	1/22 (4.5%)	1
Investigations
Blood bilirubin increased	1/22 (4.5%)	15
White blood cell decreased	1/22 (4.5%)	4
Neutrophil count decreased	2/22 (9.1%)	6
Platelet count decreased	2/22 (9.1%)	3
Alanine aminotransferase increased	1/22 (4.5%)	1
Weight loss	1/22 (4.5%)	1
Metabolism and nutrition disorders
Anorexia	2/22 (9.1%)	2
Hyperglycemia	1/22 (4.5%)	1
Hypermagnesemia	1/22 (4.5%)	1
Musculoskeletal and connective tissue disorders
Bone pain	4/22 (18.2%)	4
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain	2/22 (9.1%)	2
Nervous system disorders
Neurology, other	1/22 (4.5%)	1
Psychiatric disorders
Anxiety	2/22 (9.1%)	2
Renal and urinary disorders
Urinary retention	1/22 (4.5%)	1
Respiratory, thoracic and mediastinal disorders
Cough	3/22 (13.6%)	4
Dyspnea	2/22 (9.1%)	2
Pleural effusion	1/22 (4.5%)	1
Skin and subcutaneous tissue disorders
Purpura	1/22 (4.5%)	1
Vascular disorders
Hypertension	1/22 (4.5%)	1

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.