Solid TumorPhase 1VITACNCT00786669
A Pilot Study of the Addition of Bevacizumab to VOIT Regimen for Relapsed/Refractory Pediatric Solid Tumors
A Phase 1 study testing Bevacizumab, Temozolomide and Vincristine in people with Solid Tumor, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.
Trial summary
The purpose of this research study is to test the safety and of adding bevacizumab to the established regimen of vincristine, oral irinotecan, and temozolomide (VOIT) and see what effects it has in pediatric patients with relapsed or refractory solid tumors. Read more about this study
- Who is it for?
- Ages 1 year to 30 years
- Conditions the study is for
- Solid Tumor
- What is being tested?
- Bevacizumab, Temozolomide and Vincristine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2008to Nov 2012
- 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 1 year to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Between 1 and 30 years of age, inclusive, at the time of study entry
- Histologic verification of a solid tumor or CNS tumor at either original diagnosis or relapse. Exceptions to the requirement for biopsy include patients with primary brainstem or optic pathway tumors.
- Current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life.
- Karnofsky ≥ 50% for patients > 10 years of age and Lansky ≥ 50 for patients < 10 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score. Life expectancy must be ≥ 8 weeks.
- Agreement to use an effective contraception method during and for 30 days after treatment.
- Prior treatment with vincristine, temozolomide, or irinotecan is allowed, although patients must not have had disease progression while receiving either irinotecan or temozolomide. Prior treatment with bevacizumab is not allowed.
- Adequate Bone Marrow (Peripheral ANC ≥ 750/uL, PLT ≥ 75,000/uL transfusion independent, Hgb ≥ 8.0 gm/dL), renal (negative urine dipstick for protein, OR < 1000 mg protein/24-hour urine collection, Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2), and liver function (Bilirubin ≤ 1.5 ULN, SGPT ≤ 5 ULN, Serum albumin ≥ 2 g/dL).
- Adequate blood clotting (INR, Fibrinogen, and PTT < grade 2).
Who cannot join
- Concomitant Medications: Growth factors that support platelet or white cell number or function administered within the past 3 days, currently receiving investigational drugs, or who have received an investigational drug within the last 7 days, currently receiving other anti-cancer agents, currently taking phenobarbital, phenytoin, carbamazepine, oxcarbazepine (Trileptal), rifampin, voriconazole, itraconazole, ketoconazole or other systemically-administered azole antifungal drugs, aprepitant (Emend), or St. John's Wort, requiring antihypertensive agents at the time of enrollment, receiving medications known to inhibit platelet function or known to selectively inhibit cyclooxygenase activity, with the exception of acetaminophen.
- Require IV antibiotics at time of enrollment, or who are currently receiving treatment for Clostridium difficile infection.
- Must not have been previously diagnosed with a deep venous or arterial thrombosis (including pulmonary embolism), and must not have a known thrombophilic condition.
- Experienced arterial thromboembolic events, including transient ischemic attacks or cerebrovascular accidents, within the last year. Must not have a history of myocardial infarction, severe or unstable angina, or clinically significant peripheral vascular disease.
- Documented, chronic non-healing wound, ulcer, or bone fracture, as well as patients who have had a major surgical procedure or significant traumatic injury within 28 days prior to beginning therapy.
- Recent (within last 6 months) hemoptysis (≥ ½ teaspoon of red blood).
Trial locations and contacts
1 site in 1 country.
United States1 site
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
About this study
Official title: A Pilot Study of the Addition of Bevacizumab to Vincristine, Oral Irinotecan, and Temozolomide (VOIT Regimen) for Relapsed/Refractory Pediatric Solid Tumors
The purpose of this research study is to test the safety and of adding bevacizumab to the established regimen of vincristine, oral irinotecan, and temozolomide (VOIT) and see what effects it has in pediatric patients with relapsed or refractory solid tumors.
Read the detailed description
A recent Children's Oncology Group study evaluated the 3-drug combination of vincristine, oral irinotecan, and temozolomide (VOIT), and found it to be safe and tolerable in pediatric patients. This VOIT regimen may be useful for a variety of childhood cancers.
Additional data suggests that the beneficial effects of irinotecan can be improved by giving it with bevacizumab. Bevacizumab is a monoclonal antibody that works against a protein called "vascular endothelial growth factor" (VEGF). In cancer treatment, it is used to reduce tumor growth by blocking the formation of new blood vessels.
All of the drugs used in this study have been approved by the Food and Drug Administration (FDA) for use in adults with certain cancer types. However, the combination of drugs in this study is considered experimental because the FDA has not approved them to be used together.
Each drug has been given by itself to children before, and the combination of temozolomide, irinotecan, and vincristine has been given to children in more than one clinical trial. This is the first study in which all four of the drugs (vincristine, oral irinotecan, temozolomide, and bevacizumab) will be given together to children.
Up to 20 pediatric patients will receive therapy. The previously established bevacizumab dose of 15 mg/kg will be administered by intravenous infusion on day 1 at the start of every 3-week course. Intravenous vincristine will be given on day 1, oral irinotecan on days 1-5, and oral temozolomide on days 1-5. Courses will be repeated as frequently as every three weeks in patients who do not have evidence of disease progression and who have adequate recovery from previous courses. Cephalosporin antibiotics will be used to reduce irinotecan-associated diarrhea.
Patients will be monitored on the study for toxicity and response for up to 6 courses.
- Conditions
- Solid Tumor
- Being tested
- Bevacizumab, Temozolomide, Vincristine, Irinotecan, Cefixime
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BevacizumabDrug
Also called rhuMAb VEGF, Avastin
Bevacizumab (IV) 15 mg/Kg on day 1 every 3 weeks for up to 6 cycles
TemozolomideDrug
Also called Temodar, TEM
100 mg/m2/day po on Days 1-5 every 3 weeks for up to 6 cycles. For patients under 0.5 m2 BSA, TEM = 3.3 mg/kg/day po on Days 1-5.
VincristineDrug
Also called VCR, Oncovin
1.5 mg/m2 on Day 1 (max dose 2 mg) administered as an IV bolus every 3 weeks for up to 6 cycles. For patients <0.5 m2 BSA, VCR dose = 0.05 mg/kg (maximum dose 2 mg).
IrinotecanDrug
Also called CPT-11, Camptothecin-11, Camptosar®, IRN
90 mg/m2/day po on Days 1-5 every 3 weeks for up to 6 cycles
CefiximeDrug
Also called Suprax®, Vantin®, Cefpodoxime, CEF
8 mg/kg/day (max. daily dose 400 mg) of cefixime or 5 mg/kg/dose bid (max. daily dose 400 mg) of cefpodoxime starting Day -1 BEFORE chemotherapy and continuing EVERY DAY while on study, or for 2 days after last dose of chemotherapy if treatment stopped early for disease progression or toxicity
| Study group | Role | What they receive |
|---|---|---|
| Bevacizumab+TEM/VCR/IRN/CEF | Experimental | Bevacizumab(IV) 15 mg/Kg on day 1 every 3 weeks for up to 6 cycles
Temozolomide (TEM) 100 mg/m2/day po on Days 1-5 every 3 weeks for up to 6 cycles. For patients under 0.5 m2 BSA, TEM = 3.3 mg/kg/day po on Days 1-5.
Vincristine (VCR) 1.5 mg/m2 on Day 1 (max dose 2 mg) administered as an IV bolus every 3 weeks for up to 6 cycles. For patients <0.5 m2 BSA, VCR dose = 0.05 mg/kg (maximum dose 2 mg).
Irinotecan (IRN) 90 mg/m2/day po on Days 1-5 every 3 weeks for up to 6 cycles
Cefexime (CEF) 8 mg/kg/day (max. daily dose 400 mg) of cefixime or 5 mg/kg/dose bid (max. daily dose 400 mg) of cefpodoxime starting Day -1 BEFORE chemotherapy and continuing EVERY DAY while on study, or for 2 days after last dose of chemotherapy if treatment stopped early for disease progression or toxicity Receives: Drug: Bevacizumab; Drug: Temozolomide; Drug: Vincristine; Drug: Irinotecan; Drug: Cefixime |
What is being measured
The primary outcome is the main question the study is designed to answer.
Toxicities of adding bevacizumab to the established VOIT regimen using cefixime to reduce irinotecan-associated diarrhea.
Define the toxicities of adding bevacizumab to the established vincristine, oral irinotecan, and temozolomide (VOIT) regimen using cefixime to reduce irinotecan-associated diarrhea.
Measured: During treatment course
Secondary outcomes (3)
Preliminarily definition of the antitumor activity of this drug combination within the confines of a small pilot trial.
Preliminarily define the antitumor activity of this drug combination within the confines of a small pilot trial.
Measured: Two years
Feasibility assessment of the collection and analysis of serum DNA for methylation of the MGMT promotor.
To assess the feasibility of collecting and analyzing serum Deoxyribonucleic acid (DNA) for methylation of the methylguanine-deoxyribonucleic acid methyltransferase (MGMT) promotor.
Measured: Two years
Comparison of free and total levels of VEGF in serum following treatment with bevacizumab.
Compare free and total levels of Vascular endothelial growth factor (VEGF) in serum following treatment with bevacizumab.
Measured: Two Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2008 (estimated)
- Study startOct 2008
- Primary completionNov 2012
- Study completionNov 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid TumorStudies of the same condition, open and under way.
- More trials run by Children's Hospital Medical Center, CincinnatiThe sponsor's other registered studies.
- 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
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Medical Center, Cincinnati
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Brian Turpin, D.O., Study chair, Children's Hospital Medical Center, Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00786669
- Sponsor's protocol ID
- VITAC
- Acronym
- VITAC
- Status last verified
- Feb 2015
- First submitted
- 5 Nov 2008
- Last updated
- 10 Feb 2021
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of the Addition of Bevacizumab to Vincristine, Oral Irinotecan, and Temozolomide (VOIT Regimen) for Relapsed/Refractory Pediatric Solid Tumors
- ClinicalTrials.gov ID
- NCT00786669
- Acronym / sponsor ID
- VITAC / VITAC
- Conditions
- Solid Tumor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
- Study start
- Oct 2008
- Primary completion
- Nov 2012 (actual)
- Study completion
- Nov 2012 (actual)
- First posted
- 6 Nov 2008 (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.
The purpose of this research study is to test the safety and of adding bevacizumab to the established regimen of vincristine, oral irinotecan, and temozolomide (VOIT) and see what effects it has in pediatric patients with relapsed or refractory solid tumors.
Detailed description
A recent Children's Oncology Group study evaluated the 3-drug combination of vincristine, oral irinotecan, and temozolomide (VOIT), and found it to be safe and tolerable in pediatric patients. This VOIT regimen may be useful for a variety of childhood cancers.
Additional data suggests that the beneficial effects of irinotecan can be improved by giving it with bevacizumab. Bevacizumab is a monoclonal antibody that works against a protein called "vascular endothelial growth factor" (VEGF). In cancer treatment, it is used to reduce tumor growth by blocking the formation of new blood vessels.
All of the drugs used in this study have been approved by the Food and Drug Administration (FDA) for use in adults with certain cancer types. However, the combination of drugs in this study is considered experimental because the FDA has not approved them to be used together.
Each drug has been given by itself to children before, and the combination of temozolomide, irinotecan, and vincristine has been given to children in more than one clinical trial. This is the first study in which all four of the drugs (vincristine, oral irinotecan, temozolomide, and bevacizumab) will be given together to children.
Up to 20 pediatric patients will receive therapy. The previously established bevacizumab dose of 15 mg/kg will be administered by intravenous infusion on day 1 at the start of every 3-week course. Intravenous vincristine will be given on day 1, oral irinotecan on days 1-5, and oral temozolomide on days 1-5. Courses will be repeated as frequently as every three weeks in patients who do not have evidence of disease progression and who have adequate recovery from previous courses. Cephalosporin antibiotics will be used to reduce irinotecan-associated diarrhea.
Patients will be monitored on the study for toxicity and response for up to 6 courses.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bevacizumab+TEM/VCR/IRN/CEF | Experimental | Drug: Bevacizumab, Drug: Temozolomide, Drug: Vincristine, Drug: Irinotecan, Drug: CefiximeBevacizumab(IV) 15 mg/Kg on day 1 every 3 weeks for up to 6 cycles Temozolomide (TEM) 100 mg/m2/day po on Days 1-5 every 3 weeks for up to 6 cycles. For patients under 0.5 m2 BSA, TEM = 3.3 mg/kg/day po on Days 1-5. Vincristine (VCR) 1.5 mg/m2 on Day 1 (max dose 2 mg) administered as an IV bolus every 3 weeks for up to 6 cycles. For patients <0.5 m2 BSA, VCR dose = 0.05 mg/kg (maximum dose 2 mg). Irinotecan (IRN) 90 mg/m2/day po on Days 1-5 every 3 weeks for up to 6 cycles Cefexime (CEF) 8 mg/kg/day (max. daily dose 400 mg) of cefixime or 5 mg/kg/dose bid (max. daily dose 400 mg) of cefpodoxime starting Day -1 BEFORE chemotherapy and continuing EVERY DAY while on study, or for 2 days after last dose of chemotherapy if treatment stopped early for disease progression or toxicity |
Who may qualify
- Ages
- 1 year to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (8 listed)
- Between 1 and 30 years of age, inclusive, at the time of study entry
- Histologic verification of a solid tumor or CNS tumor at either original diagnosis or relapse. Exceptions to the requirement for biopsy include patients with primary brainstem or optic pathway tumors.
- Current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life.
- Karnofsky ≥ 50% for patients > 10 years of age and Lansky ≥ 50 for patients < 10 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score. Life expectancy must be ≥ 8 weeks.
- Agreement to use an effective contraception method during and for 30 days after treatment.
Key exclusion criteria (6 listed)
- Concomitant Medications: Growth factors that support platelet or white cell number or function administered within the past 3 days, currently receiving investigational drugs, or who have received an investigational drug within the last 7 days, currently receiving other anti-cancer agents, currently taking phenobarbital, phenytoin, carbamazepine, oxcarbazepine (Trileptal), rifampin, voriconazole, itraconazole, ketoconazole or other systemically-administered azole antifungal drugs, aprepitant (Emend), or St. John's Wort, requiring antihypertensive agents at the time of enrollment, receiving medications known to inhibit platelet function or known to selectively inhibit cyclooxygenase activity, with the exception of acetaminophen.
- Require IV antibiotics at time of enrollment, or who are currently receiving treatment for Clostridium difficile infection.
- Must not have been previously diagnosed with a deep venous or arterial thrombosis (including pulmonary embolism), and must not have a known thrombophilic condition.
- Experienced arterial thromboembolic events, including transient ischemic attacks or cerebrovascular accidents, within the last year. Must not have a history of myocardial infarction, severe or unstable angina, or clinically significant peripheral vascular disease.
- Documented, chronic non-healing wound, ulcer, or bone fracture, as well as patients who have had a major surgical procedure or significant traumatic injury within 28 days prior to beginning therapy.
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 |
|---|---|---|
| BevacizumabAlso: rhuMAb VEGF, AvastinBevacizumab (IV) 15 mg/Kg on day 1 every 3 weeks for up to 6 cycles | Drug | Bevacizumab+TEM/VCR/IRN/CEF |
| TemozolomideAlso: Temodar, TEM100 mg/m2/day po on Days 1-5 every 3 weeks for up to 6 cycles. For patients under 0.5 m2 BSA, TEM = 3.3 mg/kg/day po on Days 1-5. | Drug | Bevacizumab+TEM/VCR/IRN/CEF |
| VincristineAlso: VCR, Oncovin1.5 mg/m2 on Day 1 (max dose 2 mg) administered as an IV bolus every 3 weeks for up to 6 cycles. For patients <0.5 m2 BSA, VCR dose = 0.05 mg/kg (maximum dose 2 mg). | Drug | Bevacizumab+TEM/VCR/IRN/CEF |
| IrinotecanAlso: CPT-11, Camptothecin-11, Camptosar®, IRN90 mg/m2/day po on Days 1-5 every 3 weeks for up to 6 cycles | Drug | Bevacizumab+TEM/VCR/IRN/CEF |
| CefiximeAlso: Suprax®, Vantin®, Cefpodoxime, CEF8 mg/kg/day (max. daily dose 400 mg) of cefixime or 5 mg/kg/dose bid (max. daily dose 400 mg) of cefpodoxime starting Day -1 BEFORE chemotherapy and continuing EVERY DAY while on study, or for 2 days after last dose of chemotherapy if treatment stopped early for disease progression or toxicity | Drug | Bevacizumab+TEM/VCR/IRN/CEF |
Primary outcome
Toxicities of adding bevacizumab to the established VOIT regimen using cefixime to reduce irinotecan-associated diarrhea.
Time frame: During treatment course
Define the toxicities of adding bevacizumab to the established vincristine, oral irinotecan, and temozolomide (VOIT) regimen using cefixime to reduce irinotecan-associated diarrhea.
3 secondary outcomes
Preliminarily definition of the antitumor activity of this drug combination within the confines of a small pilot trial.
Time frame: Two years
Feasibility assessment of the collection and analysis of serum DNA for methylation of the MGMT promotor.
Time frame: Two years
Comparison of free and total levels of VEGF in serum following treatment with bevacizumab.
Time frame: Two Years
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 10 Feb 2021.
Related trials for Solid Tumor
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Neoplasms
Active, not recruitingPhase 3
A Safety and Efficacy Extension Study of Pertuzumab in Patients With Solid Tumors Previously Enrolled in a Hoffmann-La Roche-Sponsored Pertuzumab Clinical Trial
Solid Tumors
RecruitingPhase 1
IL-12 Genetically Engineered Myeloid Cells in Participants With Relapsed, Refractory Solid Tumors
Relapsed Solid Tumor Malignancies, Refractory Solid Tumor Malignancies
RecruitingObservational study
Immune Checkpoint Inhibitor Toxicity Risk Prediction in Solid Tumors
Malignant Solid Neoplasm
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.
Brian Turpin, D.O. study chair
Children's Hospital Medical Center, Cincinnati
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 Bevacizumab, Temozolomide and Vincristine in people with Solid Tumor, run by Children's Hospital Medical Center, Cincinnati 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?
The sponsor lists 8 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 10 Feb 2021. 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.
What does the primary outcome measure?
Toxicities of adding bevacizumab to the established VOIT regimen using cefixime to reduce irinotecan-associated diarrhea. (time frame: During treatment course). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 10 Feb 2021.