Zoledronic Acid (ZOMETA) With Cyclophosphamide With Neuroblastoma and Cortical Bone Involvement

NCT00206388 | Completed Phase 1 DMC

• 2 other identifiers: 16758ZOMETA
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 8

Brief Summary

The purposes of this study are:

1. 1.To find the highest dose of monthly intravenous Zometa that can be given with daily low doses of cyclophosphamide by mouth to children with recurrent or refractory neuroblastoma without causing severe side effects.
2. 2.To find out the side effects seen by giving Zometa and cyclophosphamide on this schedule at different dose levels.
3. 3.To measure blood and urine levels of Zometa during treatment
4. 4.To preliminarily evaluate the antitumor activity of Zometa and concomitant oral cyclophosphamide in children with recurrent and/or refractory neuroblastoma within the confines of a Phase I study.
5. 5.To measure the effects of Zometa on markers of bone breakdown found in urine, blood, and bone marrow
6. 6.To measure the effects of Zometa on the immune system.

Conditions

NEUROBLASTOMA

Keywords

NEUROBLASTOMA; RECURRENT; REFRACTORY; CORTICAL; BONE

Outcome Measures

Primary Outcomes (2)

• Toxicity

  28 days, lifetime for delayed toxicities

• Maximum tolerated dose (MTD)

  28 days

Secondary Outcomes (3)

• Anti tumor activity

  1-2 months post treatment

• Pharmacokinetics

  prior to infusion of first dose and 24h post

• Biologic activity

  during courses 1-4

Study Arms (1)

Zolendric acid with Cyclophosphamide

EXPERIMENTAL

Zometa will be administered intravenously every 28 days beginning on day 0. Cyclophosphamide will be administered daily without interruption (unless toxicity supervenes) beginning day 0. Each course of therapy will be 28 days. On day 0 of each cycle, cyclophosphamide should be given first, followed by Zometa with a separation between the two drugs of at least one hour. All patients are required to take calcium and Vitamin D supplementation for the duration of study participation.

Drug: Zolendric acid; Drug: Cyclophosphamide

Interventions

Zolendric acid DRUG

IV, 2mg/m2/dose on day 0

Also known as: Zometa

Zolendric acid with Cyclophosphamide

Cyclophosphamide DRUG

fixed dose of 25mg/m2/dose days 0-27

Also known as: CTX, Cytoxan

Zolendric acid with Cyclophosphamide

Eligibility Criteria

• Age: Up to 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Less than or equal to 30 years of age when enrolled on study.
• A diagnosis of neuroblastoma either by histologic verification of neuroblastoma and/or demonstration of tumor cells in the bone marrow with increased urinary catecholamines.
• High-risk neuroblastoma with at least ONE of the following: 1. Recurrent/progressive disease. 2. Refractory disease (i.e. less than a partial response to frontline therapy). No biopsy is required for eligibility for study. 3. Persistent disease after at least a partial response to frontline therapy (i.e. patient has had at least a partial response to frontline therapy but still has residual disease by MIBG, CT/MRI, or bone marrow). Patients in this category are REQUIRED to have a biopsy of at least one residual site demonstrating viable neuroblastoma.
• Bone disease demonstrated by uptake on MIBG scan. If the patient's tumor is known to be non-avid for MIBG then the patient must have evidence of either new lesions or progression of prior lesions on bone scan or plain radiographs.
• A Karnofsky or Lansky performance status of greater than or equal to 50%. Patients who are unable to walk because of paralysis or tumor pain, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• Life expectancy of greater than 2 months.
• Fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study. 1. Must not have received within 3 weeks of entry onto this study (4 weeks if prior nitrosourea). 2. Patients must not have received radiation for a minimum of four weeks prior to study entry at the site of any lesion that was biopsied to document study eligibility. A minimum of six weeks is required following prior large field radiation therapy (ie: TBI, craniospinal therapy, whole abdomen, total lung, or over 50% marrow space). 3. Patients must not have had an autologous stem cell transplant within 3 months of entry onto this study. Patients status post-allogeneic stem cell transplant are excluded. 4. A minimum of six weeks is required following prior therapeutic doses of MIBG. 5. Must not have received factors that support platelet or white cell number or function within 7 days of study entry. 6 Must not have received bisphosphonate therapy.
• Must not be receiving any other anti-cancer agents or radiotherapy at the time of study entry or while on study.
• Organ Function Requirements Adequate Bone Marrow Function: a. ANC greater than or equal to 750 b. Platelet count greater than or equal to 50,000, transfusion independent (defined as no platelet transfusion for one week). NOTE: hematologic criteria must be met by all patients, regardless of neuroblastoma involvement in bone marrow. Adequate Renal Function a. Glomerular Filtration Rate of greater than or equal to 70 ml/min/1.73 m2, OR b. Age-adjusted normal serum creatinine for age Adequate Liver Function a. Total bilirubin less than or equal to 1.5 x normal for age, and b. SGPT (ALT) and SGOT (AST) less than 5 x normal for age.
• Ionized serum calcium greater than or equal to 1.0 mmol/L (Patients are allowed to be on calcium supplements if serum calcium is stable)
• Urinalysis with less than or equal to 1+ heme.
• Reproductive Function: Negative serum beta-HCG in females and use of effective contraception in females and males of child-bearing potential.

You may not qualify if:

• Status post-ALLOGENEIC stem cell transplant.
• Received prior bisphosphonate therapy.
• Receiving other investigational agents.
• Have an uncontrolled infection.
• Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.
• Pregnancy or breast feeding.

Sponsors & Collaborators

• Baylor College of Medicine: lead
• New Approaches to Neuroblastoma Therapy Consortium: collaborator

Study Sites (8)

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

USCF School of Medicine

San Francisco, California, 94143, United States

Location

Lucille Salter Packer Children's Hospital

Stanford, California, 94305, United States

Location

Indiana University-Riley Children's Hospital

Indianapolis, Indiana, 46202, United States

Location

Cincinnati Children's Hospital

Cincinnati, Ohio, 45229, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Texas Children's Cancer Center

Houston, Texas, 77030, United States

Location

University of Wisconsin Medical Center

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Neuroblastoma; Recurrence

Interventions

Zoledronic Acid; Cyclophosphamide

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides

Study Officials

• Peter Zage, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: September 14, 2005
• First Posted: September 21, 2005
• Study Start: April 1, 2005
• Primary Completion: April 1, 2008
• Study Completion: May 1, 2013
• Last Updated: August 2, 2013

Record last verified: 2013-08

Locations

US (8)