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NEUROBLASTOMAPhase 1NCT00206388

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

A Phase 1 study testing Zolendric acid and Cyclophosphamide in people with NEUROBLASTOMA, run by Baylor College of Medicine at 8 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purposes of this study are: 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. Read more about this study

Who is it for?
Ages Up to 30 years
Conditions the study is for
NEUROBLASTOMA
What is being tested?
Zolendric acid and Cyclophosphamide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
8 sitesUnited States
Study dates
Apr 2005to May 2013
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 30 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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.
Show all 12Show fewer
  • 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.

Who cannot join

  • 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.

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites

  • Cincinnati Children's Hospital

    Cincinnati, Ohio, 45229

  • Texas Children's Cancer Center

    Houston, Texas, 77030

  • Indiana University-Riley Children's Hospital

    Indianapolis, Indiana, 46202

  • Children's Hospital Los Angeles

    Los Angeles, California, 90027

  • University of Wisconsin Medical Center

    Madison, Wisconsin, 53792

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • USCF School of Medicine

    San Francisco, California, 94143

  • Lucille Salter Packer Children's Hospital

    Stanford, California, 94305

Other trials in United States

About this study

Official title: A Phase I Study of Zoledronic Acid (Zometa) With Cyclophosphamide in Children With Recurrent or Refractory Neuroblastoma and Cortical Bone Involvement (NANT 2004-01)

The purposes of this study are:

  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. To find out the side effects seen by giving Zometa and cyclophosphamide on this schedule at different dose levels.
  3. To measure blood and urine levels of Zometa during treatment
  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. To measure the effects of Zometa on markers of bone breakdown found in urine, blood, and bone marrow
  6. To measure the effects of Zometa on the immune system.
Read the detailed description

Zoledronic Acid (Zometa), a new generation, highly potent bisphosphonate used to treat osteoporosis and hypercalcemia of malignancy, is widely used in adult malignancies with potential for bone metastasis such as breast cancer, multiple myeloma and prostate cancer. Bisphosphonates modulate the bone environment by toxicity to osteoclasts resulting in decreased bone resorption. Zometa is the first bisphosphonate to affect both osteolytic and osteoblastic metastatic lesions. In several large randomized studies in adults with recurrent or advanced malignancies, patients randomized to Zometa had delay in progression of bone metastases and less morbidity (skeletal related events) when compared to either placebo or pamidronate. The toxicity profile of Zometa in adults has been tolerable and includes hypocalcemia, temperature rise, and nausea. The most concerning toxicity is decline in renal function that appears to be related to cumulative dose and the dose rate of administration. In our pre-clinical studies bisphosphonates delayed progression of osteolytic lesions in neuroblastoma tumors xenografted into immunocompromised mice while the combination of Zometa with low dose cyclophosphamide appeared to prolong overall survival. The primary aim of this study is to evaluate the maximum tolerated dose of Zometa combined with low dose oral cyclophosphamide in children with recurrent or refractory neuroblastoma. We will also evaluate the pharmacokinetics of Zometa in children with neuroblastoma and examine the effect of Zometa on markers of bone resorption, cytokines and bone-related growth factors.

Conditions
NEUROBLASTOMA
Being tested
Zolendric acid, Cyclophosphamide
Keywords
NEUROBLASTOMA, RECURRENT, REFRACTORY, CORTICAL, BONE
Medical subject headings
Neuroblastoma, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Zolendric acidDrug

    Also called Zometa

    IV, 2mg/m2/dose on day 0

  • CyclophosphamideDrug

    Also called CTX, Cytoxan

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

Study groups in NCT00206388
Study groupRoleWhat they receive
Zolendric acid with CyclophosphamideExperimentalZometa 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.
Receives: Drug: Zolendric acid; Drug: Cyclophosphamide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Toxicity

    Measured: 28 days, lifetime for delayed toxicities

  2. Maximum tolerated dose (MTD)

    Measured: 28 days

Secondary outcomes (3)

  1. Anti tumor activity

    Measured: 1-2 months post treatment

  2. Pharmacokinetics

    Measured: prior to infusion of first dose and 24h post

  3. Biologic activity

    Measured: during courses 1-4

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Sep 2005 (estimated)
  2. Study startApr 2005
  3. Primary completionApr 2008
  4. Study completionMay 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00206388
Sponsor's protocol ID
16758
Other IDs
ZOMETA
Status last verified
Aug 2013
First submitted
14 Sep 2005
Last updated
2 Aug 2013
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Zolendric acid and Cyclophosphamide in people with NEUROBLASTOMA, run by Baylor College of Medicine at 8 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Aug 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Toxicity (time frame: 28 days, lifetime for delayed toxicities). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00206388.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Aug 2013.

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