Refractory Solid TumorsPhase 1NCT00665990
Phase I Study of Bevacizumab and Sorafenib Combined With Low Dose Cyclophosphamide in Patients With Refractory Solid Tumors and Leukemia
A Phase 1 study testing Bevacizumab, Sorafenib and Cyclophosphamide in people with Refractory Solid Tumors and Leukemia, run by St. Jude Children's Research Hospital at 1 site in United States.
Trial summary
Phase I Study of Bevacizumab and Sorafenib Combined with Low Dose Cyclophosphamide in Patients with Refractory Solid Tumors and Leukemia. Patients with solid tumors (including central nervous tumors) that are recurrent or refractory to standard therapy, or for whom standard therapy is not available. Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Refractory Solid Tumors, Leukemia
- What is being tested?
- Bevacizumab, Sorafenib and Cyclophosphamide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2007to Aug 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 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- NOTE: As of May 2013, enrollment of solid tumor participants was completed. Participants with a diagnosis of leukemia continue to be enrolled.
- Diagnosis: Solid tumors, including central nervous system tumors and lymphomas, that are recurrent or refractory to standard therapy or for which there is no standard therapy. Histologic verification of diagnosis is required.
- Age: < or = 21 years of age at the time of original diagnosis
- Life expectancy: at least 8 weeks
- Performance status: Karnofsky > or = 50 for > 10 years of age; Lansky > or = 50 for children < or = 10 years of age.
- Organ Function: Must have adequate organ and marrow function
Show all 17Show fewer
- Prior Therapy: Patient must have fully recovered from the acute toxic effects of all prior therapy prior to enrolling on study.
- Must not have current or recent use of full-dose anticoagulants
- Must not have received medications known to inhibit platelet function or known to selectively inhibit cyclooxygenase-2 (COX-2) activity
- Bevacizumab and sorafenib should not be administered to pregnant women.
- Pregnancy tests must be obtained in girls who are > 10 years of age or post-menarchal.
- Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
- Breast feeding should be discontinued if a mother wishes to participate in this study.
- Patients with a documented, chronic non-healing wound, ulcer, or bone fracture or history of a major surgical procedure or significant traumatic injury within 28 days prior to beginning therapy should be excluded due to preclinical evidence supporting the potential for delayed wound healing.
- Patients must not have a deep venous or arterial thrombosis (including pulmonary embolism) within the last three months prior to study entry, and must not have a known thrombophilic condition
- Patients must not have a history of myocardial infarction, severe or unstable angina, or severe peripheral vascular disease.
- Ability to understand and willingness of research participant or legal guardian/representative to give written informed consent.
Who cannot join
- Body surface area < 0.3 m2
- Presence of a known bleeding diathesis or coagulopathy
- Patients with evidence of intra-tumoral central nervous system hemorrhage. in current scans. Patients are required to have a head CT or MRI within 2 weeks prior to study enrollment.
- Patients with known hypersensitivity to other recombinant human antibodies
- Patients who have an uncontrolled infection
- Patients with recurrent or refractory leukemia will be excluded from the dose escalation component of the phase I trial.
Trial locations and contacts
1 site in 1 country.
United States1 site
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
About this study
Phase I Study of Bevacizumab and Sorafenib Combined with Low Dose Cyclophosphamide in Patients with Refractory Solid Tumors and Leukemia. Patients with solid tumors (including central nervous tumors) that are recurrent or refractory to standard therapy, or for whom standard therapy is not available. Once a maximum tolerated dose (MTD) has been established in patients with recurrent or refractory solid tumors, the tolerability of this dose will be tested in patients with refractory or recurrent leukemia and an expanded cohort of patients with refractory or recurrent solid tumors.
Read the detailed description
Phase I Study of Bevacizumab and Sorafenib Combined with Low Dose Cyclophosphamide in Patients with Refractory Solid Tumors and Leukemia. Patients with solid tumors (including central nervous tumors) that are recurrent or refractory to standard therapy, or for whom standard therapy is not available. Once a maximum tolerated dose (MTD) has been established in patients with recurrent or refractory solid tumors, the tolerability of this dose will be tested in a maximum of 6 patients, in cohorts of 3, with refractory or recurrent leukemia and a maximum of 24 evaluable patients, in cohorts of 6, with refractory or recurrent solid tumors.
Approximately 21-24 patients with refractory solid tumors to define the maximum tolerated dose (MTD) and 6 patients with recurrent or refractory leukemia,12 patients with refractory or recurrent bone or soft tissue sarcomas and 12 patients with other refractory or recurrent solid tumors (including lymphomas) to test the tolerability of this MTD in patients with hematological malignancies. Bevacizumab will be administered intravenously at a starting dose of 5 mg/kg every 3 weeks with sorafenib by mouth every 12 hrs at a starting dose of 90 mg/m2 every 12 hours and cyclophosphamide by mouth daily at a dose of 50 mg/m2/day (dose level 1). A course of therapy will be considered to be of 21 days duration. Once a maximum tolerated dose of sorafenib (sMTD) in combination with bevacizumab and cyclophosphamide has been determined, 6 patients with recurrent or refractory leukemia will be then be evaluated at the solid tumor MTD to test the tolerability of this combination in patients with hematological malignancies.
- Conditions
- Refractory Solid Tumors, Leukemia
- Being tested
- Bevacizumab, Sorafenib, Cyclophosphamide
- Medical subject headings
- Leukemia
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(R)
Bevacizumab starting dose of 5 mg/kg every 3 weeks increasing in combination with Sorafenib and Cyclophosphamide until maximum tolerated dose
SorafenibDrug
Also called BAY-43-9006, Nexavar(R)
Sorafenib 90 mg/m2 PO every 12 hours increasing in combination with Bevacizumab and Cyclophosphamide until maximum tolerated dose
CyclophosphamideDrug
Also called Cytoxan(R)
Cyclophosphamide 50 mg/m2 PO once daily increasing in combination with Bevacizumab and Sorafenib until maximum tolerated dose
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Other | All participants will receive bevacizumab, sorafenib, and cyclophosphamide until maximum tolerated dose is reached. Receives: Drug: Bevacizumab; Drug: Sorafenib; Drug: Cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine the maximum tolerated dose and dose limiting toxicity of bevacizumab and sorafenib administered in combination with low dose cyclophosphamide to patients with refractory solid tumors.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2008 (estimated)
- Study startNov 2007
- Primary completionAug 2013
- Study completionAug 2013
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 Refractory Solid TumorsStudies of the same condition, open and under way.
- More trials run by St. Jude Children's Research HospitalThe 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
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Jude Children's Research Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sara Federico, MD, Principal investigator, St. Jude Children' Research Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00665990
- Sponsor's protocol ID
- ANGIO1
- Other IDs
- NCI-2011-01146
- Status last verified
- Jan 2015
- First submitted
- 22 Apr 2008
- Last updated
- 9 Jan 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
McCarville MB, Coleman JL, Guo J, Li Y, Li X, Honnoll PJ, Davidoff AM, Navid F. Use of Quantitative Dynamic Contrast-Enhanced Ultrasound to Assess Response to Antiangiogenic Therapy in Children and Adolescents With Solid Malignancies: A Pilot Study. AJR Am J Roentgenol. 2016 May;206(5):933-9. doi: 10.2214/AJR.15.15789. Epub 2016 Mar 21.
PubMed 26999488
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Bevacizumab and Sorafenib Combined With Low Dose Cyclophosphamide in Patients With Refractory Solid Tumors and Leukemia
- ClinicalTrials.gov ID
- NCT00665990
- Acronym / sponsor ID
- ANGIO1
- Conditions
- Refractory Solid Tumors, Leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- St. Jude Children's Research HospitalUniversity, hospital or other
- Study start
- Nov 2007
- Primary completion
- Aug 2013 (actual)
- Study completion
- Aug 2013 (actual)
- First posted
- 24 Apr 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.
Phase I Study of Bevacizumab and Sorafenib Combined with Low Dose Cyclophosphamide in Patients with Refractory Solid Tumors and Leukemia. Patients with solid tumors (including central nervous tumors) that are recurrent or refractory to standard therapy, or for whom standard therapy is not available. Once a maximum tolerated dose (MTD) has been established in patients with recurrent or refractory solid tumors, the tolerability of this dose will be tested in patients with refractory or recurrent leukemia and an expanded cohort of patients with refractory or recurrent solid tumors.
Detailed description
Phase I Study of Bevacizumab and Sorafenib Combined with Low Dose Cyclophosphamide in Patients with Refractory Solid Tumors and Leukemia. Patients with solid tumors (including central nervous tumors) that are recurrent or refractory to standard therapy, or for whom standard therapy is not available. Once a maximum tolerated dose (MTD) has been established in patients with recurrent or refractory solid tumors, the tolerability of this dose will be tested in a maximum of 6 patients, in cohorts of 3, with refractory or recurrent leukemia and a maximum of 24 evaluable patients, in cohorts of 6, with refractory or recurrent solid tumors.
Approximately 21-24 patients with refractory solid tumors to define the maximum tolerated dose (MTD) and 6 patients with recurrent or refractory leukemia,12 patients with refractory or recurrent bone or soft tissue sarcomas and 12 patients with other refractory or recurrent solid tumors (including lymphomas) to test the tolerability of this MTD in patients with hematological malignancies. Bevacizumab will be administered intravenously at a starting dose of 5 mg/kg every 3 weeks with sorafenib by mouth every 12 hrs at a starting dose of 90 mg/m2 every 12 hours and cyclophosphamide by mouth daily at a dose of 50 mg/m2/day (dose level 1). A course of therapy will be considered to be of 21 days duration. Once a maximum tolerated dose of sorafenib (sMTD) in combination with bevacizumab and cyclophosphamide has been determined, 6 patients with recurrent or refractory leukemia will be then be evaluated at the solid tumor MTD to test the tolerability of this combination in patients with hematological malignancies.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment | Other | Drug: Bevacizumab, Drug: Sorafenib, Drug: CyclophosphamideAll participants will receive bevacizumab, sorafenib, and cyclophosphamide until maximum tolerated dose is reached. |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (17 listed)
- NOTE: As of May 2013, enrollment of solid tumor participants was completed. Participants with a diagnosis of leukemia continue to be enrolled.
- Diagnosis: Solid tumors, including central nervous system tumors and lymphomas, that are recurrent or refractory to standard therapy or for which there is no standard therapy. Histologic verification of diagnosis is required.
- Age: < or = 21 years of age at the time of original diagnosis
- Life expectancy: at least 8 weeks
- Performance status: Karnofsky > or = 50 for > 10 years of age; Lansky > or = 50 for children < or = 10 years of age.
Key exclusion criteria (6 listed)
- Body surface area < 0.3 m2
- Presence of a known bleeding diathesis or coagulopathy
- Patients with evidence of intra-tumoral central nervous system hemorrhage. in current scans. Patients are required to have a head CT or MRI within 2 weeks prior to study enrollment.
- Patients with known hypersensitivity to other recombinant human antibodies
- Patients who have an uncontrolled infection
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, Avastin(R)Bevacizumab starting dose of 5 mg/kg every 3 weeks increasing in combination with Sorafenib and Cyclophosphamide until maximum tolerated dose | Drug | Treatment |
| SorafenibAlso: BAY-43-9006, Nexavar(R)Sorafenib 90 mg/m2 PO every 12 hours increasing in combination with Bevacizumab and Cyclophosphamide until maximum tolerated dose | Drug | Treatment |
| CyclophosphamideAlso: Cytoxan(R)Cyclophosphamide 50 mg/m2 PO once daily increasing in combination with Bevacizumab and Sorafenib until maximum tolerated dose | Drug | Treatment |
Primary outcome
Determine the maximum tolerated dose and dose limiting toxicity of bevacizumab and sorafenib administered in combination with low dose cyclophosphamide to patients with refractory solid tumors.
Time frame: 3 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 9 Jan 2015.
- Derived from this study: PubMed 26999488McCarville MB, Coleman JL, Guo J, Li Y, Li X, Honnoll PJ, Davidoff AM, Navid F. Use of Quantitative Dynamic Contrast-Enhanced Ultrasound to Assess Response to Antiangiogenic Therapy in Children and Adolescents With Solid Malignancies: A Pilot Study. AJR Am J Roentgenol. 2016 May;206(5):933-9. doi: 10.2214/AJR.15.15789. Epub 2016 Mar 21.
- St. Jude Children's Research HospitalLink provided by the sponsor.
- Clinical Trials Open at St. JudeLink provided by the sponsor.
Related trials for Refractory 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
Active, not recruitingPhase 2
Testing AZD5363 as a Potential Targeted Treatment in Cancers With AKT Genetic Changes (MATCH-Subprotocol Y)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm
Active, not recruitingPhase 2
Testing GDC-0032 (Taselisib) as a Potential Targeted Treatment in Cancers With PIK3CA Genetic Changes (MATCH-Subprotocol I)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm
RecruitingPhase 1
A Study With NKT3964 for Adults With Advanced/Metastatic Solid Tumors
Solid Tumor, Advanced Solid Tumor
Active, not recruitingPhase 2
Testing MLN0128 (TAK-228) as Potentially Targeted Treatment in Cancers With TSC1 or TSC2 Genetic Changes (MATCH - Subprotocol M)
Advanced Lymphoma, Advanced 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.
Sara Federico, MD principal investigator
St. Jude Children' Research Hospital
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, Sorafenib and Cyclophosphamide in people with Refractory Solid Tumors and Leukemia, run by St. Jude Children's Research Hospital 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 17 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 9 Jan 2015. 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?
Determine the maximum tolerated dose and dose limiting toxicity of bevacizumab and sorafenib administered in combination with low dose cyclophosphamide to patients with refractory solid tumors. (time frame: 3 years). 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 NCT00665990, 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 9 Jan 2015.