Breast CancerPhase 1/2NCT00616122
Sunitinib, Cyclophosphamide, and Methotrexate in Treating Patients With Metastatic Breast Cancer
A Phase 1/2 study testing cyclophosphamide, methotrexate and sunitinib malate in people with Breast Cancer, run by University of California, San Francisco at 1 site in United States.
Trial summary
RATIONALE: Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cyclophosphamide and methotrexate, 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 18 to 120 years
- Conditions the study is for
- Breast Cancer
- What is being tested?
- cyclophosphamide, methotrexate and sunitinib malate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Mar 2006to 1 Dec 2012
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Pathologically confirmed diagnosis of breast cancer with documented progressive disease
- Metastatic disease
- Measurable disease as defined by RECIST criteria or evaluable disease
- Must have received at least one prior chemotherapy regimen for metastatic breast cancer
- Patients refusing all other chemotherapy for breast cancer may enroll without prior treatment
- Patients with HER2-overexpression disease must have been previously treated with trastuzumab (Herceptin®)
- Patients with stable brain metastases are eligible
- Hormone receptor status not specified
PATIENT CHARACTERISTICS:
- Menopausal status not specified
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Life expectancy ≥ 12 weeks
- Absolute Neutrophil Count (ANC) ≥ 1,000/mm³
- Platelet count ≥ 100,000/mm³
- Creatinine ≤ 1.5 times upper limit of normal (ULN)
- aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times ULN (≤ 5 times ULN in the presence of liver metastases)
- Total bilirubin ≤ 1.5 times ULN
- Able to take oral medications and maintain hydration
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 6 months after treatment
- No severe concurrent illness including, but not limited to, any of the following:
- Congestive heart failure
- Significant cardiac disease
- Uncontrolled hypertension
- Must be able to read and speak English
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- At least 2 weeks since prior treatment, including chemotherapy, hormonal therapy, trastuzumab (Herceptin®), or other targeted therapies
- Prior bevacizumab allowed if discontinued for any reason other than toxicity
- No potent inducers or inhibitors of CYP3A4 enzymes that effect the metabolism of sunitinib malate
- No prior sunitinib malate
- No other concurrent investigational therapy
- No concurrent radiotherapy
- Concurrent bisphosphonates allowed
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, San Francisco
San Francisco, California, 94115
About this study
Official title: Phase I/II Study of SU11248 (Sutent) in Combination With Metronomic Dosing of Cyclophosphamide and Methotrexate in Patients With Metastatic Breast Cancer
RATIONALE: Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cyclophosphamide and methotrexate, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving sunitinib together with combination chemotherapy may kill more tumor cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of sunitinib when given together with cyclophosphamide and methotrexate to see how well they work in treating patients with metastatic breast cancer.
Read the detailed description
OBJECTIVES:
Primary
- To determine the maximum tolerated dose of the combination of metronomic dose cyclophosphamide and methotrexate with continuous dosing sunitinib malate. (Phase I)
- To determine the time to disease progression in patients with metastatic breast cancer treated with metronomic dose chemotherapy with cyclophosphamide and methotrexate combined with continuous dosing of sunitinib malate. (Phase II)
Secondary
- To determine the response rate in patients receiving this treatment.
- To determine the duration of response in patients receiving this treatment.
- To determine the toxicity of this regimen in these patients.
- To determine the feasibility by assessment of toxicities of this regimen and number of voluntary withdrawals from the study.
- To correlate outcome measures with possible surrogate markers including serial measurements of circulating tumor cells and circulating endothelial cells.
OUTLINE: This is a dose-escalation study of sunitinib malate.
- Phase I: Patients receive oral sunitinib malate once daily. Beginning 14 days later, patients also receive oral cyclophosphamide once daily on days 1-21 and oral methotrexate twice daily on days 1, 2, 8, 9, 15, and 16. Treatment with sunitinib malate, cyclophosphamide, and methotrexate repeats every 21 days* in the absence of disease progression or unacceptable toxicity.
- Phase II: Patients receive sunitinib malate at the maximum tolerated dose determined in phase I and cyclophosphamide and methotrexate as in phase I.
NOTE: *Course 1 includes 2 weeks of sunitinib malate alone followed by sunitinib malate, cyclophosphamide, and methotrexate for 21 days
Blood samples are collected periodically for measurement of circulating tumor cells, circulating endothelial cells, and vascular endothelial growth factor (VEGF) levels.
After completion of study treatment, patients are followed for 30 days and then every 2 months for 1 year.
- Conditions
- Breast Cancer
- Being tested
- cyclophosphamide, methotrexate, sunitinib malate, laboratory biomarker analysis
- Keywords
- recurrent breast cancer, stage IV breast cancer, male breast cancer
- Medical subject headings
- Breast Neoplasms, Breast Neoplasms, Male
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cyclophosphamideDrug
methotrexateDrug
sunitinib malateDrug
laboratory biomarker analysisOther
| Study group | Role | What they receive |
|---|---|---|
| Sunitinib, Cyclophosphamide, and Methotrexate | Experimental | Not described Receives: Drug: cyclophosphamide; Drug: methotrexate; Drug: sunitinib malate; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose of Sunitinib (Phase I)
Patients in each cohort were followed for DLT for at least 8 weeks (2 week lead-in with sunitinib and 6 weeks of treatment with sunitinib and metronomic cyclophosphamide and methotrexate) before opening accrual to the next dose level. Dose limiting toxicity (DLT) defined as: 1) ≥ grade 3 anemia that does not resolve with appropriate growth factors afebrile grade 4 neutropenia that does not resolve with growth factor support after ≥ 7 days 2) grade 4 neutropenia associated with fever (1 reading of oral temperature > 38.5 degrees Celsius or 3 readings of oral temperature > 38.0 degrees Celsius in a 24 hour period) 3) ≥ grade 3 thrombocytopenia 4) ≥ grade 3 non-hematologic toxicities, except those that can be controlled to grade 2 or less with appropriate treatment.
- Inability to resume treatment with any of the study medications within 14 days of stopping due to treatment related toxicity.
Measured: 8 weeks
Patients With Progression-free Survival (PFS) Greater Than or Equal to 12 Weeks (Phase II)
Progression defined as: 25% increase or an increase of 10 sq. cm (whichever is smaller) in the sum of products of measurable lesions over smallest sum observed (over baseline if no decrease), or appearance of any lesion which had disappeared, or clear worsening of any evaluable disease, or appearance of any new lesion/site, or failure to return for evaluation due to deteriorating condition (unless deterioration is clearly unrelated to this cancer).
Measured: up to 12 weeks after treatment start date
Secondary outcomes (2)
Overall Response Rate
Per Response Evaluation Criteria in Solid Tumors (RECIST): Complete Response (CR): Complete disappearance of all measurable and evaluable disease. No new lesions.
Partial Response (PR): greater than or equal to 50% decrease under baseline in the sum of the products of perpendicular diameters of all measurable lesions. No progression of evaluable disease. No new lesions.
Stable: Does not qualify for complete response, partial response or progression.
Measured: until disease progression, up to 13 months post treatment
Duration of Response
Duration of response refers to duration of single partial response observed per Response Evaluation Criteria in Solid Tumors (RECIST):
Complete Response (CR): Complete disappearance of all measurable and evaluable disease. No new lesions.
Partial Response (PR): greater than or equal to 50% decrease under baseline in the sum of the products of perpendicular diameters of all measurable lesions. No progression of evaluable disease. No new lesions.
Stable: Does not qualify for complete response, partial response or progression.
Progression: 25% increase or an increase of 10 sq. cm (whichever is smaller) in the sum of products of measurable lesions over smallest sum observed (over baseline if no decrease), OR appearance of any lesion which had disappeared, or clear worsening of any evaluable disease, or appearance of any new lesion/site, or failure to return for evaluation due to deteriorating condition (unless deterioration is clearly unrelated to this cancer).
Measured: until disease progression up to 13 months post treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2008 (estimated)
- Study start1 Mar 2006
- Primary completion1 Mar 2011
- Study completion1 Dec 2012
Why it stopped: Risk to benefit ratio not acceptable
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Hope S. Rugo, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00616122
- Sponsor's protocol ID
- 057519
- Other IDs
- NCI-2011-01275
- Status last verified
- Dec 2019
- First submitted
- 14 Feb 2008
- Last updated
- 13 Jan 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study of SU11248 (Sutent) in Combination With Metronomic Dosing of Cyclophosphamide and Methotrexate in Patients With Metastatic Breast Cancer
- ClinicalTrials.gov ID
- NCT00616122
- Acronym / sponsor ID
- 057519
- Conditions
- Breast Cancer
- Keywords
- recurrent breast cancer, stage IV breast cancer, male breast cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Risk to benefit ratio not acceptable
- Enrolment
- 32 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 1 Mar 2006 (actual)
- Primary completion
- 1 Mar 2011 (actual)
- Study completion
- 1 Dec 2012 (actual)
- First posted
- 15 Feb 2008 (estimated)
- Results
- Posted 12 Feb 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cyclophosphamide and methotrexate, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving sunitinib together with combination chemotherapy may kill more tumor cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of sunitinib when given together with cyclophosphamide and methotrexate to see how well they work in treating patients with metastatic breast cancer.
Detailed description
OBJECTIVES:
Primary
- To determine the maximum tolerated dose of the combination of metronomic dose cyclophosphamide and methotrexate with continuous dosing sunitinib malate. (Phase I)
- To determine the time to disease progression in patients with metastatic breast cancer treated with metronomic dose chemotherapy with cyclophosphamide and methotrexate combined with continuous dosing of sunitinib malate. (Phase II)
Secondary
- To determine the response rate in patients receiving this treatment.
- To determine the duration of response in patients receiving this treatment.
- To determine the toxicity of this regimen in these patients.
- To determine the feasibility by assessment of toxicities of this regimen and number of voluntary withdrawals from the study.
- To correlate outcome measures with possible surrogate markers including serial measurements of circulating tumor cells and circulating endothelial cells.
OUTLINE: This is a dose-escalation study of sunitinib malate.
- Phase I: Patients receive oral sunitinib malate once daily. Beginning 14 days later, patients also receive oral cyclophosphamide once daily on days 1-21 and oral methotrexate twice daily on days 1, 2, 8, 9, 15, and 16. Treatment with sunitinib malate, cyclophosphamide, and methotrexate repeats every 21 days* in the absence of disease progression or unacceptable toxicity.
- Phase II: Patients receive sunitinib malate at the maximum tolerated dose determined in phase I and cyclophosphamide and methotrexate as in phase I.
NOTE: *Course 1 includes 2 weeks of sunitinib malate alone followed by sunitinib malate, cyclophosphamide, and methotrexate for 21 days
Blood samples are collected periodically for measurement of circulating tumor cells, circulating endothelial cells, and vascular endothelial growth factor (VEGF) levels.
After completion of study treatment, patients are followed for 30 days and then every 2 months for 1 year.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sunitinib, Cyclophosphamide, and Methotrexate | Experimental | Drug: cyclophosphamide, Drug: methotrexate, Drug: sunitinib malate, Other: laboratory biomarker analysis |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older 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 |
|---|---|---|
| cyclophosphamide | Drug | Sunitinib, Cyclophosphamide, and Methotrexate |
| methotrexate | Drug | Sunitinib, Cyclophosphamide, and Methotrexate |
| sunitinib malate | Drug | Sunitinib, Cyclophosphamide, and Methotrexate |
| laboratory biomarker analysis | Other | Sunitinib, Cyclophosphamide, and Methotrexate |
Primary outcome
Maximum Tolerated Dose of Sunitinib (Phase I)
Time frame: 8 weeks
Patients in each cohort were followed for DLT for at least 8 weeks (2 week lead-in with sunitinib and 6 weeks of treatment with sunitinib and metronomic cyclophosphamide and methotrexate) before opening accrual to the next dose level. Dose limiting toxicity (DLT) defined as: 1) ≥ grade 3 anemia that does not resolve with appropriate growth factors afebrile grade 4 neutropenia that does not resolve with growth factor support after ≥ 7 days 2) grade 4 neutropenia associated with fever (1 reading of oral temperature > 38.5 degrees Celsius or 3 readings of oral temperature > 38.0 degrees Celsius in a 24 hour period) 3) ≥ grade 3 thrombocytopenia 4) ≥ grade 3 non-hematologic toxicities, except those that can be controlled to grade 2 or less with appropriate treatment. 5) Inability to resume treatment with any of the study medications within 14 days of stopping due to treatment related toxicity.
Patients With Progression-free Survival (PFS) Greater Than or Equal to 12 Weeks (Phase II)
Time frame: up to 12 weeks after treatment start date
Progression defined as: 25% increase or an increase of 10 sq. cm (whichever is smaller) in the sum of products of measurable lesions over smallest sum observed (over baseline if no decrease), or appearance of any lesion which had disappeared, or clear worsening of any evaluable disease, or appearance of any new lesion/site, or failure to return for evaluation due to deteriorating condition (unless deterioration is clearly unrelated to this cancer).
2 secondary outcomes
Overall Response Rate
Time frame: until disease progression, up to 13 months post treatment
Duration of Response
Time frame: until disease progression up to 13 months post treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Hope S. Rugo, MD principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing cyclophosphamide, methotrexate and sunitinib malate in people with Breast Cancer, run by University of California, San Francisco 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: stopped early, as of the sponsor's last update on 13 Jan 2020. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Feb 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 Sunitinib (Phase I) (time frame: 8 weeks). 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?
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 13 Jan 2020.