Unspecified Adult Solid Tumor, Protocol SpecificPhase 1NCT00884676
Ixabepilone and Sunitinib Malate in Treating Patients With Progressive Advanced Solid Tumors
A Phase 1 study testing Ixabepilone and Sunitinib in people with Unspecified Adult Solid Tumor, Protocol Specific, run by Jaime Merchan at 1 site in United States.
Trial summary
RATIONALE: Drugs used in chemotherapy, such as ixabepilone, 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
- Unspecified Adult Solid Tumor, Protocol Specific
- What is being tested?
- Ixabepilone and Sunitinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2008to Jul 2015
- 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 18 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Non-hematological malignancy that has progressed on standard therapy.
- Age > 18.
- ECOG Performance Status (PS) 0, 1, or 2.
- Life expectancy of > 3 months.
- More than three prior systemic therapy regimens (a period of 4 weeks from chemotherapy or immunotherapy ("washout period"), must have elapsed; and 2 weeks for prior tyrosine kinase inhibitors).
- Prior treatment with sunitinib in a 4 weeks on/2weeks off schedule is acceptable.
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- Women of Child Bearing Potential (WOCBP) must use adequate method of contraception throughout and up to 4 weeks after the study.
- Patients must have either measurable disease (defined in Section 9.0) or evaluable disease (bony lesions, pleural effusion, ascites)
- Required laboratory values obtained <= 7 days prior to registration:
- Granulocytes (ANC) >= 1500/mm3
- PLT >= 100,000/mm3
- Hgb >= 9.0 g/dL
- Direct bilirubin <= 1.0 x ULN
- Alkaline phosphatase <= 2.5 x ULN (<= 5 x if liver metastasis is present)
- AST/ALT <= 2.5 x ULN (<= 5 x if liver metastasis is present)
- Creatinine < 1.5 x ULN
- Pregnancy Test Negative (For WOCBP*)
- Urinalysis - Urine protein/creatinine ratio < 1, or < 1+ protein**
- TSH = WNL
- INR <= 1.5, unless the patient is on full dose warfarin or stable dose of LMW heparin with a therapeutic INR of > 1.5, <= 3.
- Urine protein should be screened by random urine protein:creatinine ratio. For urine protein: creatinine ratio >1.0, 24-hour urine protein should be obtained and the level should be < 1000 mg for patient enrollment.
- Capable of understanding the investigational nature, potential risks and benefits of the study and able to provide valid informed consent.
- Willingness to donate blood for correlative marker studies.
- If a patient is on full-dose anticoagulants, the following criteria should be met for enrollment:
- The subject must have an in-range INR (usually between 2 and 3) on a stable dose of warfarin or on stable dose of LMW heparin.
- No active bleeding or pathological conditions that carry high risk of bleeding (e.g. tumor involving major vessels, known varices).
Who cannot join
- Patients with symptomatic/untreated CNS metastases. Patients with known CNS metastases can be enrolled if:
- CNS metastases have been appropriately treated. Treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; Gamma Knife, LINAC, or equivalent) or resection as deemed appropriate by the treating physician. Patients who had surgical resection of CNS metastases or brain biopsy within 3 months prior to Day 1 will be excluded.
- No ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period.
- No evidence of progression or hemorrhage after treatment (brain imaging study within 4 weeks of treatment start).
- CTC Grade 2 or greater neuropathy (motor or sensory) at study entry.
- Inability to swallow capsules.
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- History of gastrointestinal disease, malabsorption, or requiring use of a feeding tube.
- Patients who have received any investigational compound within the past 28 days (within 2 weeks for prior RTKI treated patients).
- Patients who have received radiotherapy for any cause less than 4 weeks prior to study entry.
- Patients taking cytochrome P450 (CYP) 3A4 enzyme-inducing or enzyme-inhibitor medications like: antiepileptic drugs (phenytoin, carbamazepine or phenobarbital), St John's Wort, ketoconazole, dexamethasone, dysrhythmic drugs (terfenadine, quinidine, procainamide, sotalol, probucolol, bepridil, indapamide, or flecainide), haloperidol, risperidone, rifampin, grapefruit (or juice) within two weeks of registration and during the course of therapy. Topical and inhaled steroids are permitted. Please refer to Appendix VI for a complete list of CYP34A inducers and inhibitors.
- Patients with known HIV infection are excluded due to the possibility of unknown side effects on the immune system by these agents. The potential impact of pharmacokinetic interactions of anti-retroviral therapy with ixabepilone or sunitinib is unknown. Appropriate studies may be undertaken in patients with HIV and those receiving combination anti-retroviral therapy in the future.
- Invasive procedures defined as follows:
- Major surgical procedure, open biopsy or significant traumatic injury <= 28 days prior to registration.
- Anticipation of need for major surgical procedures during the course of the study.
- Core biopsy <= 7 days prior to registration.
- Port placement <= 7 days prior to registration.
- Serious or non-healing wound, ulcer or bone fracture.
- History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess <= 28 days.
- Evidence of bleeding diathesis or coagulopathy.
- Ongoing hemoptysis, or cerebrovascular accident <= previous 6 months, or peripheral vascular disease with claudication on < 1 block, or history of clinically significant bleeding.
- Significant cardiovascular disease defined as congestive heart failure (New York Heart Association Class II, III or IV), angina pectoris requiring nitrate therapy, or recent myocardial infarction (<= the last 6 months). Patients must have an absolute baseline left ventricular ejection fraction (LVEF) >= 50% by MUGA scan within 4 weeks prior to registration
- Uncontrolled hypertension (defined as a blood pressure of > 150 mmHg systolic and/or > 90 mmHg diastolic on medication).
- A currently active second malignancy other than non-melanoma skin cancer. Patients are not considered to have a currently active malignancy if they have completed anti-cancer therapy and are considered by their physician to be at less than 30% risk of relapse.
- Any of the following, as this regimen may be harmful to a developing fetus or nursing child:
- Pregnant women
- Breastfeeding women
- Men or women of childbearing potential or their sexual partners who are unwilling to employ adequate contraception (diaphragm, birth control pills, injections, intrauterine device [IUD], surgical sterilization, subcutaneous implants, or abstinence, etc.) NOTE: The effects of the agent(s) on the developing human fetus at the recommended therapeutic dose are unknown.
- Other uncontrolled serious medical or psychiatric condition (e.g. cardiac arrhythmias, diabetes, etc.)
- Patients must not have ongoing ventricular cardiac dysrhythmias of NCI CTCAE Version 3.0 grade >= 2. Patients with a history of serious ventricular arrhythmia (VT or VF >= 3 beats in a row) are also excluded. Additionally, patients with ongoing atrial fibrillation are not eligible.
- Patients must have a QTc interval < 500 msec on baseline EKG.
- Prior treatment with ixabepilone.
- History of chronic or recurrent infection that requires continuous use of anti-viral, anti-fungal or anti-bacterial therapy; or foreseeable need to receive anti-infective therapy within 14 days of Cycle 1 Day 1 treatment.
- History of Grade 3/4 hypersensitivity reaction to Cremophor EL or its derivatives (polyoxyethylated castor oil).
- Non-small cell lung cancer (NSCLC) of squamous cell type, or NSCLC of any histology that involves a major blood vessel (e.g. aorta, pulmonary artery, etc)
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Miami Sylvester Comprehensive Cancer Center
Miami, Florida, 33136
About this study
Official title: A Phase I Trial of Weekly and Every Three Weeks Ixabepilone and Sunitinib in Solid Tumor Patients
RATIONALE: Drugs used in chemotherapy, such as ixabepilone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.
PURPOSE: This phase I trial is studying the side effects and best dose of ixabepilone when given together with sunitinib malate in treating patients with progressive advanced solid tumors.
Read the detailed description
OBJECTIVES:
Primary
- To determine the safety and toxicity profile of ixabepilone in combination with sunitinib malate in patients with progressive, advanced non-hematologic malignancies.
- To determine the recommended phase II dose of ixabepilone given weekly versus once every three weeks in combination with a fixed dose of sunitinib malate in these patients.
Secondary
- To evaluate the pharmacokinetic profiles of the combination of ixabepilone and sunitinib malate and correlate them with activity and/or toxicity.
- To obtain preliminary efficacy data (complete response, partial response, or stable disease) of these treatment combinations.
- To correlate changes in angiogenesis biomarkers with clinical (safety and efficacy) and pharmacokinetic parameters in patients treated with these drug combinations.
- To estimate the optimal biological dose.
OUTLINE: This is a dose escalation study of ixabepilone. Patients are assigned to 1 of 2 treatment groups.
- Schedule A: Patients receive ixabepilone IV on days 1, 8, and 15. Beginning on day 8 of course 1, patients also receive oral sunitinib malate once daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
- Schedule B: Patients receive ixabepilone IV on day 1. Beginning on day 8 of course 1, patients also receive oral sunitinib malate once daily. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Blood samples are collected periodically for biomarker and pharmacokinetic studies by flow cytometry.
After completion of study therapy, patients are followed at 30 days and every 3 months for 1 year.
- Being tested
- Ixabepilone, Sunitinib
- Keywords
- unspecified adult solid tumor, protocol specific
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IxabepiloneDrug
Also called BMS-247550, Ixempra, Azaepothilone B, epothilone B lactam
Administered intravenously. Dosage assigned by Phase I center as determined by dose-escalation schedule:
- Schedule A: Weekly for 3 weeks each cycle (Days 1, 8 and 15)
- Schedule B: Day 1 of each 3-week cycle.
SunitinibDrug
Also called Sunitinib Malate, Sutent, Butanedioic acid
For both Schedules A and B, daily, orally, starting on Day 8 of Cycle 1
| Study group | Role | What they receive |
|---|---|---|
| Schedule A | Experimental | Schedule A: Ixabepilone - Weekly for 3 weeks each cycle (Days 1, 8 and 15) For both Schedules A and B, Sunitinib daily, orally, starting on Day 8 of Cycle 1 Receives: Drug: Ixabepilone; Drug: Sunitinib |
| Schedule B | Experimental | Ixabepilone - Day 1 of each 3-week cycle For both Schedules A and B, Sunitinib daily, orally, starting on Day 8 of Cycle 1. Receives: Drug: Ixabepilone; Drug: Sunitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and toxicity profile as assessed by NCI CTCAE version 3.0
Measured: Approximately 18-30 months
Recommended Phase II dose of Ixabepilone when administered with Sunitinib
Measured: Schedule A (12 - 18 months); Schedule B (6 -12 months after Schedule A)
Secondary outcomes (4)
Pharmacokinetic profiles of Ixabepilone and Sunitinib malate and correlation with activity and/or toxicity
Measured: Approximately 18-30 months
Efficacy data (complete response, partial response, or stable disease) of these treatment combinations
Measured: Approximately 18-30 months
Correlation of changes in angiogenesis biomarkers with clinical (safety and efficacy) and pharmacokinetic parameters
Measured: Approximately 18-30 months
Estimation of optimal biological dose
Measured: Approximately 18-30 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2009 (estimated)
- Study startNov 2008
- Primary completionNov 2013
- Study completionJul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Unspecified Adult Solid Tumor, Protocol SpecificStudies 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
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jaime Merchan
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb, Pfizer
- Responsible party
- Sponsor-investigator, Jaime Merchan, University of Miami
- Investigators
- Jaime R. Merchan, MD, Principal investigator, University of Miami
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00884676
- Sponsor's protocol ID
- 20080376
- Other IDs
- GA6181ZB, CA163159
- Status last verified
- Jul 2015
- First submitted
- 18 Apr 2009
- Last updated
- 9 Oct 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial of Weekly and Every Three Weeks Ixabepilone and Sunitinib in Solid Tumor Patients
- ClinicalTrials.gov ID
- NCT00884676
- Acronym / sponsor ID
- 20080376
- Keywords
- unspecified adult solid tumor, protocol specific
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Jaime MerchanUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb, Pfizer
- Study start
- Nov 2008
- Primary completion
- Nov 2013 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 21 Apr 2009 (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: Drugs used in chemotherapy, such as ixabepilone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.
PURPOSE: This phase I trial is studying the side effects and best dose of ixabepilone when given together with sunitinib malate in treating patients with progressive advanced solid tumors.
Detailed description
OBJECTIVES:
Primary
- To determine the safety and toxicity profile of ixabepilone in combination with sunitinib malate in patients with progressive, advanced non-hematologic malignancies.
- To determine the recommended phase II dose of ixabepilone given weekly versus once every three weeks in combination with a fixed dose of sunitinib malate in these patients.
Secondary
- To evaluate the pharmacokinetic profiles of the combination of ixabepilone and sunitinib malate and correlate them with activity and/or toxicity.
- To obtain preliminary efficacy data (complete response, partial response, or stable disease) of these treatment combinations.
- To correlate changes in angiogenesis biomarkers with clinical (safety and efficacy) and pharmacokinetic parameters in patients treated with these drug combinations.
- To estimate the optimal biological dose.
OUTLINE: This is a dose escalation study of ixabepilone. Patients are assigned to 1 of 2 treatment groups.
- Schedule A: Patients receive ixabepilone IV on days 1, 8, and 15. Beginning on day 8 of course 1, patients also receive oral sunitinib malate once daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
- Schedule B: Patients receive ixabepilone IV on day 1. Beginning on day 8 of course 1, patients also receive oral sunitinib malate once daily. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Blood samples are collected periodically for biomarker and pharmacokinetic studies by flow cytometry.
After completion of study therapy, patients are followed at 30 days and every 3 months for 1 year.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Schedule A | Experimental | Drug: Ixabepilone, Drug: SunitinibSchedule A: Ixabepilone - Weekly for 3 weeks each cycle (Days 1, 8 and 15) For both Schedules A and B, Sunitinib daily, orally, starting on Day 8 of Cycle 1 |
| Schedule B | Experimental | Drug: Ixabepilone, Drug: SunitinibIxabepilone - Day 1 of each 3-week cycle For both Schedules A and B, Sunitinib daily, orally, starting on Day 8 of Cycle 1. |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- Non-hematological malignancy that has progressed on standard therapy.
- Age > 18.
- ECOG Performance Status (PS) 0, 1, or 2.
- Life expectancy of > 3 months.
- More than three prior systemic therapy regimens (a period of 4 weeks from chemotherapy or immunotherapy ("washout period"), must have elapsed; and 2 weeks for prior tyrosine kinase inhibitors).
Key exclusion criteria (34 listed)
- Patients with symptomatic/untreated CNS metastases. Patients with known CNS metastases can be enrolled if:
- CNS metastases have been appropriately treated. Treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; Gamma Knife, LINAC, or equivalent) or resection as deemed appropriate by the treating physician. Patients who had surgical resection of CNS metastases or brain biopsy within 3 months prior to Day 1 will be excluded.
- No ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period.
- No evidence of progression or hemorrhage after treatment (brain imaging study within 4 weeks of treatment start).
- CTC Grade 2 or greater neuropathy (motor or sensory) at study entry.
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 |
|---|---|---|
| IxabepiloneAlso: BMS-247550, Ixempra, Azaepothilone B, epothilone B lactamAdministered intravenously. Dosage assigned by Phase I center as determined by dose-escalation schedule: * Schedule A: Weekly for 3 weeks each cycle (Days 1, 8 and 15) * Schedule B: Day 1 of each 3-week cycle. | Drug | Schedule A, Schedule B |
| SunitinibAlso: Sunitinib Malate, Sutent, Butanedioic acidFor both Schedules A and B, daily, orally, starting on Day 8 of Cycle 1 | Drug | Schedule A, Schedule B |
Primary outcome
Safety and toxicity profile as assessed by NCI CTCAE version 3.0
Time frame: Approximately 18-30 months
Recommended Phase II dose of Ixabepilone when administered with Sunitinib
Time frame: Schedule A (12 - 18 months); Schedule B (6 -12 months after Schedule A)
4 secondary outcomes
Pharmacokinetic profiles of Ixabepilone and Sunitinib malate and correlation with activity and/or toxicity
Time frame: Approximately 18-30 months
Efficacy data (complete response, partial response, or stable disease) of these treatment combinations
Time frame: Approximately 18-30 months
Correlation of changes in angiogenesis biomarkers with clinical (safety and efficacy) and pharmacokinetic parameters
Time frame: Approximately 18-30 months
Estimation of optimal biological dose
Time frame: Approximately 18-30 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 9 Oct 2015.
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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.
Jaime R. Merchan, MD principal investigator
University of Miami
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 Ixabepilone and Sunitinib in people with Unspecified Adult Solid Tumor, Protocol Specific, run by Jaime Merchan 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 26 inclusion and 34 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 Oct 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?
Safety and toxicity profile as assessed by NCI CTCAE version 3.0 (time frame: Approximately 18-30 months). 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 9 Oct 2015.