Brain and Central Nervous System TumorsPhase 1NCT00303940
Talabostat Combined With Temozolomide or Carboplatin in Treating Young Patients With Relapsed or Refractory Brain Tumors or Other Solid Tumors
A Phase 1 study testing carboplatin, talabostat mesylate and temozolomide in people with Brain and Central Nervous System Tumors and Childhood Germ Cell Tumor, run by National Institutes of Health Clinical Center (CC) at 1 site in United States.
Trial summary
RATIONALE: Talabostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as temozolomide and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Read more about this study
- Who is it for?
- Ages 2 to 18 years
- Conditions the study is for
- Brain and Central Nervous System Tumors, Childhood Germ Cell Tumor, Kidney Cancer
- What is being tested?
- carboplatin, talabostat mesylate and temozolomide
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2005to Feb 2010
- 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 2 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
DISEASE CHARACTERISTICS:
- Histologically confirmed solid tumors, including, but not limited to, any of the following:
- Rhabdomyosarcoma and other soft tissue sarcomas
- Ewing's sarcoma family of tumors
- Osteosarcoma
- Neuroblastoma
- Wilms' tumor
- Hepatic tumors
- Germ cell tumors
- Primary brain tumors
- In patients with brainstem or optic gliomas, requirement for histological confirmation can be waived if biopsy was not performed
- Patients with brainstem gliomas that did not respond to therapy but that are without radiographic evidence of disease progression must have clinical evidence of progression
- Patients with brain tumors must be on stable or tapering dose of corticosteroids for 7 days prior to study entry
- Measurable or evaluable disease
- Relapsed or failed to respond to frontline curative therapy, including any of the following:
- Surgery
- Radiotherapy
- Chemotherapy
- Combination of modalities
- No other potentially curative treatment options available
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- Absolute neutrophil count ≥ 1,500/mm^3
- Hemoglobin ≥ 8 mg/dL
- Platelet count ≥ 100,000/mm^3 (platelet transfusion independent)
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- SGPT ≤ 2.5 times ULN
- Creatinine clearance ≥ 60 mL/min OR age-adjusted creatinine* as follows:
- No more than 0.8 mg/dL (for patients ≤ 5 years of age)
- No more than 1.0 mg/dL (for patients 6 to 10 years of age)
- No more than 1.2 mg/dL (for patients 11 to 15 years of age)
- No more than 1.5 mg/dL (for patients > 15 years of age) NOTE: *For patients receiving carboplatin a nuclear glomerular filtration rate study, 24-hour urine collection, and serum creatinine for estimation of creatinine clearance is required if under 15 years of age OR serum creatinine and weight for estimation of creatinine clearance is required if 15-18 years of age
- Patients with history of seizures eligible if seizures controlled by anticonvulsants
- No clinically significant, unrelated systemic illness, including either of the following:
- Serious infections
- Hepatic, renal, or other organ dysfunction that would preclude study treatment
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No generalized pitting peripheral edema
- No sensitivity to valine-proline boronic acid
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Recovered to ≤ grade 1 from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to study entry
- Any number of prior chemotherapy regimens allowed
- Prior temozolomide or carboplatin as frontline therapy or in the adjuvant setting allowed provided patient did not experience severe toxicities related to the drug and tumor progressed during this therapy
- At least 3 weeks since last dose of all myelosuppressive chemotherapy
- At least 7 days since last dose of anticancer biologic agents (e.g., retinoids)
- At least 30 days since prior investigational agents
- At least 4 weeks since prior radiotherapy to > 25% of marrow-containing bones (pelvis, spine, or skull) (2 weeks for palliative [limited-port] radiotherapy)
- At least 2 months since prior autologous stem cell transplantation and recovered
- At least 1 week since prior filgrastim (G-CSF), sargramostim (GM-CSF), or epoetin alfa
- At least 2 weeks since prior pegfilgrastim
- No history of allogeneic stem cell transplantation
- No other concurrent anticancer chemotherapy, radiation therapy, or immunotherapy
- No other concurrent investigational agents
Trial locations and contacts
1 site in 1 country.
United States1 site
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, Maryland, 20892-1182
About this study
Official title: A Phase I Trial and Pharmacokinetic Study of Talabostat (PT-100, Val-Boro-Pro) in Combination With Temozolomide or Carboplatin in Pediatric Patients With Relapsed or Refractory Solid Tumors Including Brain Tumors
RATIONALE: Talabostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as temozolomide and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving talabostat together with temozolomide or carboplatin may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of talabostat when given together with temozolomide or carboplatin in treating young patients with relapsed or refractory brain tumors or other solid tumors.
Read the detailed description
OBJECTIVES:
Primary
- Determine the dose of talabostat, when used in combination with either temozolomide or carboplatin, at which maximum plasma dipeptidyl peptidase IV enzyme inhibition is achieved (in the absence of talabostat-related dose-limiting toxicity) in pediatric patients with refractory or relapsed solid tumors, including brain tumors.
- Determine the maximum tolerated dose of talabostat, when used in combination with temozolomide or carboplatin in pediatric patients, if dose-limiting toxicity attributed to talabostat is observed.
- Define the toxicity profile of talabostat when used in combination with temozolomide or carboplatin.
- Describe the pharmacokinetic profile of talabostat in pediatric patients.
Secondary
- Study levels, at baseline and after drug administration, of serum cytokines (interleukin [IL]-2, IL-6, IL-10, filgrastim [G-CSF], tumor necrosis factor-α, IL-1β, IL-8, IP10, and thrombospondin) that may be important in the immune-mediated antitumor effect of talabostat.
- Evaluate the antitumor effect of talabostat in combination with temozolomide or carboplatin on pediatric solid tumors by direct assessment of tumor response.
- Study the effect of talabostat on neutrophil function.
- Evaluate the expression of fibroblast activation protein (FAP) in pediatric tumors using immunohistochemistry to detect FAP in paraffin-embedded tissue sections from existing tumor specimens, when available.
OUTLINE: This is a dose-escalation study of talabostat. Patients are stratified according to tumor histology and prior therapy.
Based on stratification, patients receive either oral temozolomide on days 1-5 or carboplatin IV over 30 minutes on days 1-2. Patients also receive oral talabostat on days 7-20. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. (Closed to accrual as of 5/25/2009)
Cohorts of 2-6 patients receive escalating doses of talabostat until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 or < 4 of 12 patients experience dose-limiting toxicity during the first course of therapy.
PROJECTED ACCRUAL: A total of 26 patients will be accrued for this study.
- Conditions
- Brain and Central Nervous System Tumors, Childhood Germ Cell Tumor, Kidney Cancer, Liver Cancer, Neuroblastoma, Ovarian Cancer
- Being tested
- carboplatin, talabostat mesylate, temozolomide, pharmacological study
- Keywords
- unspecified childhood solid tumor, protocol specific, recurrent childhood rhabdomyosarcoma, recurrent childhood soft tissue sarcoma, recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor, recurrent osteosarcoma, recurrent neuroblastoma, recurrent Wilms tumor and other childhood kidney tumors, recurrent childhood malignant germ cell tumor, recurrent childhood liver cancer, recurrent childhood brain stem glioma, recurrent childhood cerebellar astrocytoma, recurrent childhood cerebral astrocytoma, recurrent childhood ependymoma, recurrent childhood medulloblastoma, recurrent childhood supratentorial primitive neuroectodermal tumor, childhood atypical teratoid/rhabdoid tumor, childhood low-grade cerebral astrocytoma, childhood high-grade cerebral astrocytoma, childhood choroid plexus tumor, childhood craniopharyngioma
- Medical subject headings
- Central Nervous System Neoplasms, Kidney Neoplasms, Liver Neoplasms, Neuroblastoma, Ovarian Neoplasms, Sarcoma, Neuroectodermal Tumors, Primitive, Peripheral, Osteosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
carboplatinDrug
talabostat mesylateDrug
temozolomideDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2006 (estimated)
- Study startDec 2005
- Study completionFeb 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Brain and Central Nervous System TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Enrolment
- 26 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Institutes of Health Clinical Center (CC)
- Sponsor type
- US National Institutes of Health
- Collaborators
- National Cancer Institute (NCI)
- Investigators
- Holly Meany, MD, Study chair, National Cancer Institute (NCI)Elizabeth Fox, MD, Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00303940
- Sponsor's protocol ID
- 050239
- Other IDs
- 05-C-0239, NCI-P6672, CDR0000462620
- Status last verified
- Mar 2012
- First submitted
- 15 Mar 2006
- Last updated
- 15 Mar 2012
- Results posted
- No
Publications
Meany H, Balis FM, Aikin A, Whitcomb P, Murphy RF, Steinberg SM, Widemann BC, Fox E. Pediatric phase I trial design using maximum target inhibition as the primary endpoint. J Natl Cancer Inst. 2010 Jun 16;102(12):909-12. doi: 10.1093/jnci/djq174. Epub 2010 May 11.
PubMed 20460632
Study at a glance
From the registry record, last updated by the sponsor on 15 Mar 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial and Pharmacokinetic Study of Talabostat (PT-100, Val-Boro-Pro) in Combination With Temozolomide or Carboplatin in Pediatric Patients With Relapsed or Refractory Solid Tumors Including Brain Tumors
- ClinicalTrials.gov ID
- NCT00303940
- Acronym / sponsor ID
- 050239
- Conditions
- Brain and Central Nervous System Tumors, Childhood Germ Cell Tumor, Kidney Cancer, Liver Cancer, Neuroblastoma, Ovarian Cancer
- Keywords
- unspecified childhood solid tumor, protocol specific, recurrent childhood rhabdomyosarcoma, recurrent childhood soft tissue sarcoma, recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor, recurrent osteosarcoma, recurrent neuroblastoma, recurrent Wilms tumor and other childhood kidney tumors, recurrent childhood malignant germ cell tumor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (estimated)
- Lead sponsor
- National Institutes of Health Clinical Center (CC)US National Institutes of Health
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Dec 2005
- Study completion
- Feb 2010 (actual)
- First posted
- 17 Mar 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Talabostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as temozolomide and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving talabostat together with temozolomide or carboplatin may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of talabostat when given together with temozolomide or carboplatin in treating young patients with relapsed or refractory brain tumors or other solid tumors.
Detailed description
OBJECTIVES:
Primary
- Determine the dose of talabostat, when used in combination with either temozolomide or carboplatin, at which maximum plasma dipeptidyl peptidase IV enzyme inhibition is achieved (in the absence of talabostat-related dose-limiting toxicity) in pediatric patients with refractory or relapsed solid tumors, including brain tumors.
- Determine the maximum tolerated dose of talabostat, when used in combination with temozolomide or carboplatin in pediatric patients, if dose-limiting toxicity attributed to talabostat is observed.
- Define the toxicity profile of talabostat when used in combination with temozolomide or carboplatin.
- Describe the pharmacokinetic profile of talabostat in pediatric patients.
Secondary
- Study levels, at baseline and after drug administration, of serum cytokines (interleukin [IL]-2, IL-6, IL-10, filgrastim [G-CSF], tumor necrosis factor-α, IL-1β, IL-8, IP10, and thrombospondin) that may be important in the immune-mediated antitumor effect of talabostat.
- Evaluate the antitumor effect of talabostat in combination with temozolomide or carboplatin on pediatric solid tumors by direct assessment of tumor response.
- Study the effect of talabostat on neutrophil function.
- Evaluate the expression of fibroblast activation protein (FAP) in pediatric tumors using immunohistochemistry to detect FAP in paraffin-embedded tissue sections from existing tumor specimens, when available.
OUTLINE: This is a dose-escalation study of talabostat. Patients are stratified according to tumor histology and prior therapy.
Based on stratification, patients receive either oral temozolomide on days 1-5 or carboplatin IV over 30 minutes on days 1-2. Patients also receive oral talabostat on days 7-20. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. (Closed to accrual as of 5/25/2009)
Cohorts of 2-6 patients receive escalating doses of talabostat until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 or < 4 of 12 patients experience dose-limiting toxicity during the first course of therapy.
PROJECTED ACCRUAL: A total of 26 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 2 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| carboplatin | Drug | – |
| talabostat mesylate | Drug | – |
| temozolomide | Drug | – |
| pharmacological study | Other | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 2012.
- Results publication: PubMed 20460632Meany H, Balis FM, Aikin A, Whitcomb P, Murphy RF, Steinberg SM, Widemann BC, Fox E. Pediatric phase I trial design using maximum target inhibition as the primary endpoint. J Natl Cancer Inst. 2010 Jun 16;102(12):909-12. doi: 10.1093/jnci/djq174. Epub 2010 May 11.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Holly Meany, MD study chair
National Cancer Institute (NCI)
Elizabeth Fox, MD principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing carboplatin, talabostat mesylate and temozolomide in people with Brain and Central Nervous System Tumors and Childhood Germ Cell Tumor, run by National Institutes of Health Clinical Center (CC) at 1 site 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?
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 15 Mar 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00303940, which also lists 1 linked publication.
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 15 Mar 2012.