Solid TumorsPhase 1NCT01135563
Study of Vinblastine and Sirolimus in Children With Recurrent/Refractory Solid Tumours Including CNS Tumours
A Phase 1 study testing Vinblastine and Sirolimus in people with Solid Tumors and Central Nervous System Tumors, run by The Hospital for Sick Children at 5 sites in 2 countries.
Trial summary
This study is a Phase I study using vinblastine and sirolimus in patients with relapsed solid tumors including selected brain tumors and lymphoma. The investigators hypothesis is that the combination administration of weekly vinblastine and sirolimus is safe. Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Solid Tumors, Central Nervous System Tumors
- What is being tested?
- Vinblastine and Sirolimus
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 5 sitesin 2 countries
- Study dates
- Apr 2010to Apr 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 Up to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age: 0-21 years at the time of diagnosis
- Diagnosis: Histologic verification at either the time of original diagnosis or relapse of solid tumor including CNS tumors or lymphomas
- Disease Status: All refractory/recurrent solid tumors including CNS tumors (all Diffuse Intrinsic Brain Stem Gliomas excluded) and lymphomas that have relapsed after, or are refractory to, a chemotherapy-containing treatment regimen
- Measurable disease:
- Measurable tumor by CT or MRI defined as >10 mm by spiral CT in at least one dimension
- Current disease state must be one for which there is currently no known curative therapy
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- A negative urine pregnancy test is required for female participants of child bearing potential
- Organ Function Requirements:
- adequate liver function as defined by AST or ALT < 5 x upper limit of normal, bilirubin ≤1.5 X upper limit of normal
- adequate renal function: Serum creatinine < 1.5 X upper limit of normal for age
- Adequate Bone Marrow Function Defined as:
- ANC ≥ 1000/mm3, platelets ≥ 75,000/mm3 and hemoglobin ≥ 90 g/L
- Transfusions are permitted to meet these platelet and Hgb criteria, if the patient is known to have a history of bone marrow involvement with tumor
- Patients with platelet counts < 75,000/ mm3 who are refractory to platelet transfusions are not eligible for this study
- Patients requiring transfusions of platelets or RBC to meet eligibility criteria will not be evaluable for platelet or hgb/hct hematological toxicity
- Lansky Play Score (for patients < 16 years of age) must be more than 50 and/or ECOG performance status (for patients ≥ 16 years of age) must be 0 to 2
- Specific requirements for Neuroblastoma patients Stratum:
- MIBG scan with positive uptake at minimum of one site (MIBG not required if subject's neuroblastoma is previously determined to not uptake MIBG and no measurable disease)
- Bone marrow with tumor cells seen on routine morphology (not by NSE staining only) of bilateral aspirate and /or biopsy on one bone marrow sample
- Written informed consent
Who cannot join
- Lansky score <50%
- Investigational Drugs: Patients who are currently receiving another investigational drug(s)
- Previous treatment with Vinblastine and/or mTor inhibitors
- Anti-cancer Agents: Patients who are currently receiving other anticancer agents. Patients must have fully recovered from the effects of prior chemotherapy, generally at least 3 weeks from the most recent administration (6 weeks for nitrosoureas)
- Infection: Patients who have an uncontrolled infection are not eligible until the infection is judged to be well controlled
- Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study, or in whom compliance is likely to be suboptimal
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- One week from usage of hematopoietic Growth Factor
- Patients who are refractory to platelet transfusions
- Brain Stem Glioma patients
Trial locations and contacts
5 sites in 2 countries.
5 sites in 2 countries
United States3 sites
Fletcher Allen Health Care
Burlington, Vermont, 05401
Rady Children's Hospital-San Diego
San Diego, California, 92123
SSM Cardinal Glennon Children's Medical Center
St Louis, Missouri, 63104
Canada2 sites
CHU Sainte-Justine
Montreal, Quebec, H3T 1C5
The Hospital for Sick Children
Toronto, Ontario, M5G 1X8
About this study
Official title: A Phase I Study of Vinblastine and Sirolimus in Pediatric Patients With Recurrent or Refractory Solid Tumors Including CNS Tumors
This study is a Phase I study using vinblastine and sirolimus in patients with relapsed solid tumors including selected brain tumors and lymphoma. The investigators hypothesis is that the combination administration of weekly vinblastine and sirolimus is safe.
Read the detailed description
Published data demonstrating a survival advantage of the vinblastine-sirolimus regimen vs single agent in an orthopotic neuroblastoma mouse model and our unpublished data support a VBL in vitro pro-apoptotic plasma concentration of 1-2 nM range and an anti angiogenic concentration of 2pM. These plasma concentrations are achievable with a 6 mg/m2 (apoptosis) and 1 mg/m2 VBL regimen (anti-angiogenesis) weekly regimen. We expect that vinblastine delivered at any given dose, as described in the protocol, will carry both anti-apoptotic and antiangiogenic activity. Safety and preliminary efficacy of both drugs in pediatric tumors support the development of a clinical trial.
- Conditions
- Solid Tumors, Central Nervous System Tumors
- Being tested
- Vinblastine and Sirolimus
- Keywords
- pediatrics, Solid Tumors, CNS Tumors, Vinblastine, Sirolimus, Recurrent, Refractory
- Medical subject headings
- Central Nervous System Neoplasms, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vinblastine and SirolimusDrug
Also called Vinblastine Sulfate Injection, Rapamune
Patients will be enrolled to receive vinblastine and sirolimus in 28 day cycles. Using the 3+3 standard Phase1 design, vinblastine will be administered via IV push on Days 1, 8, 15, 22. The starting dose of 4 mg/m2 (Dose Level 1) is 67% of the established MTD (6 mg/m2) for this schedule in pediatrics. Dose escalation will take place in a standard 3+3 design, in which doses will increase by approximately 20 to 25% in successive 3-patient cohorts.
Sirolimus (rapamycin) will be given by mouth (tablet or suspension) once daily throughout the cycle. Ideally patients will remain on the same dose form (tablet or suspension) for the duration of the study. All patients will be assigned a target sirolimus serum trough
| Study group | Role | What they receive |
|---|---|---|
| Vinblastine and Sirolimus | Experimental | The standard 3+3 Phase 1 trial design will be used for the conduct of this study. Three to six patients can be concurrently enrolled onto a dose level. Accrual is suspended when a cohort of three has been enrolled until toxicity data for that cohort have been reported, or when the study endpoints have been met. Receives: Drug: Vinblastine and Sirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose of vinblastine in combination with sirolimus
Maximum tolerated dose (as defined by protocol) of vinblastine in combination with sirolimus
Measured: 12 months
Secondary outcomes (2)
Safety data
Safety data will be described for all patients receiving at least one dose of vinblastine and sirolimus. Safety data will include values for hematology, serum chemistry, vital signs, and adverse events. The proportion of patients experiencing adverse events, serious adverse events, dose limiting toxicities and treatment delays will be summarized for each dosing cohort.
Measured: 12 months
Response Rate
The proportion of patients experiencing progressive disease, stable disease, partial responses or complete responses will be summarized in tabular format. Progression free survival and duration of any responses will also be summarized.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2010 (estimated)
- Study startApr 2010
- Primary completionApr 2012
- Study completionApr 2012
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 Solid TumorsStudies of the same condition, open and under way.
- More trials run by The Hospital for Sick ChildrenThe 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
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Hospital for Sick Children
- Sponsor type
- University, hospital or other
- Collaborators
- Solving Kids' Cancer
- Responsible party
- Principal investigator, Sylvain Baruchel, The Hospital for Sick Children
- Investigators
- Sylvain Baruchel, MD, Principal investigator, The Hospital for Sick Children, Toronto Canada
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01135563
- Sponsor's protocol ID
- 1000016324
- Status last verified
- Sep 2019
- First submitted
- 1 Jun 2010
- Last updated
- 20 Sep 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Morgenstern DA, Marzouki M, Bartels U, Irwin MS, Sholler GL, Gammon J, Yankanah R, Wu B, Samson Y, Baruchel S. Phase I study of vinblastine and sirolimus in pediatric patients with recurrent or refractory solid tumors. Pediatr Blood Cancer. 2014 Jan;61(1):128-33. doi: 10.1002/pbc.24656. Epub 2013 Aug 17.
PubMed 23956145
Study at a glance
From the registry record, last updated by the sponsor on 20 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Vinblastine and Sirolimus in Pediatric Patients With Recurrent or Refractory Solid Tumors Including CNS Tumors
- ClinicalTrials.gov ID
- NCT01135563
- Acronym / sponsor ID
- 1000016324
- Conditions
- Solid Tumors, Central Nervous System Tumors
- Keywords
- pediatrics, Solid Tumors, CNS Tumors, Vinblastine, Sirolimus, Recurrent, Refractory
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- The Hospital for Sick ChildrenUniversity, hospital or other
- Collaborators
- Solving Kids' Cancer
- Study start
- Apr 2010
- Primary completion
- Apr 2012 (actual)
- Study completion
- Apr 2012 (actual)
- First posted
- 2 Jun 2010 (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.
This study is a Phase I study using vinblastine and sirolimus in patients with relapsed solid tumors including selected brain tumors and lymphoma. The investigators hypothesis is that the combination administration of weekly vinblastine and sirolimus is safe.
Detailed description
Published data demonstrating a survival advantage of the vinblastine-sirolimus regimen vs single agent in an orthopotic neuroblastoma mouse model and our unpublished data support a VBL in vitro pro-apoptotic plasma concentration of 1-2 nM range and an anti angiogenic concentration of 2pM. These plasma concentrations are achievable with a 6 mg/m2 (apoptosis) and 1 mg/m2 VBL regimen (anti-angiogenesis) weekly regimen. We expect that vinblastine delivered at any given dose, as described in the protocol, will carry both anti-apoptotic and antiangiogenic activity. Safety and preliminary efficacy of both drugs in pediatric tumors support the development of a clinical trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Vinblastine and Sirolimus | Experimental | Drug: Vinblastine and SirolimusThe standard 3+3 Phase 1 trial design will be used for the conduct of this study. Three to six patients can be concurrently enrolled onto a dose level. Accrual is suspended when a cohort of three has been enrolled until toxicity data for that cohort have been reported, or when the study endpoints have been met. |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (20 listed)
- Age: 0-21 years at the time of diagnosis
- Diagnosis: Histologic verification at either the time of original diagnosis or relapse of solid tumor including CNS tumors or lymphomas
- Disease Status: All refractory/recurrent solid tumors including CNS tumors (all Diffuse Intrinsic Brain Stem Gliomas excluded) and lymphomas that have relapsed after, or are refractory to, a chemotherapy-containing treatment regimen
- Measurable disease:
- Current disease state must be one for which there is currently no known curative therapy
Key exclusion criteria (9 listed)
- Lansky score <50%
- Investigational Drugs: Patients who are currently receiving another investigational drug(s)
- Previous treatment with Vinblastine and/or mTor inhibitors
- Anti-cancer Agents: Patients who are currently receiving other anticancer agents. Patients must have fully recovered from the effects of prior chemotherapy, generally at least 3 weeks from the most recent administration (6 weeks for nitrosoureas)
- Infection: Patients who have an uncontrolled infection are not eligible until the infection is judged to be well controlled
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 |
|---|---|---|
| Vinblastine and SirolimusAlso: Vinblastine Sulfate Injection, RapamunePatients will be enrolled to receive vinblastine and sirolimus in 28 day cycles. Using the 3+3 standard Phase1 design, vinblastine will be administered via IV push on Days 1, 8, 15, 22. The starting dose of 4 mg/m2 (Dose Level 1) is 67% of the established MTD (6 mg/m2) for this schedule in pediatrics. Dose escalation will take place in a standard 3+3 design, in which doses will increase by approximately 20 to 25% in successive 3-patient cohorts. Sirolimus (rapamycin) will be given by mouth (tablet or suspension) once daily throughout the cycle. Ideally patients will remain on the same dose form (tablet or suspension) for the duration of the study. All patients will be assigned a target sirolimus serum trough | Drug | Vinblastine and Sirolimus |
Primary outcome
Maximum tolerated dose of vinblastine in combination with sirolimus
Time frame: 12 months
Maximum tolerated dose (as defined by protocol) of vinblastine in combination with sirolimus
2 secondary outcomes
Safety data
Time frame: 12 months
Response Rate
Time frame: 12 months
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 20 Sep 2019.
- Background: PubMed 23956145Morgenstern DA, Marzouki M, Bartels U, Irwin MS, Sholler GL, Gammon J, Yankanah R, Wu B, Samson Y, Baruchel S. Phase I study of vinblastine and sirolimus in pediatric patients with recurrent or refractory solid tumors. Pediatr Blood Cancer. 2014 Jan;61(1):128-33. doi: 10.1002/pbc.24656. Epub 2013 Aug 17.
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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.
Sylvain Baruchel, MD principal investigator
The Hospital for Sick Children, Toronto Canada
5 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Vinblastine and Sirolimus in people with Solid Tumors and Central Nervous System Tumors, run by The Hospital for Sick Children at 5 sites in 2 countries.
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 20 inclusion and 9 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 20 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States, Canada. 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?
Maximum tolerated dose of vinblastine in combination with sirolimus (time frame: 12 months). 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 NCT01135563, 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 20 Sep 2019.