Ixabepilone and Sunitinib Malate in Treating Patients With Progressive Advanced Solid Tumors

NCT00884676 | Completed Phase 1 DMC

• 3 other identifiers: 20080376GA6181ZBCA163159
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Keywords

unspecified adult solid tumor, protocol specific

Outcome Measures

Primary Outcomes (2)

• Safety and toxicity profile as assessed by NCI CTCAE version 3.0

  Approximately 18-30 months

• Recommended Phase II dose of Ixabepilone when administered with Sunitinib

  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

  Approximately 18-30 months

• Efficacy data (complete response, partial response, or stable disease) of these treatment combinations

  Approximately 18-30 months

• Correlation of changes in angiogenesis biomarkers with clinical (safety and efficacy) and pharmacokinetic parameters

  Approximately 18-30 months

• Estimation of optimal biological dose

  Approximately 18-30 months

Study Arms (2)

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

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.

Drug: Ixabepilone; Drug: Sunitinib

Interventions

Ixabepilone DRUG

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.

Also known as: BMS-247550, Ixempra, Azaepothilone B, epothilone B lactam, Epothilone-B BMS 247550

Schedule A; Schedule B

Sunitinib DRUG

For both Schedules A and B, daily, orally, starting on Day 8 of Cycle 1

Also known as: Sunitinib Malate, Sutent, Butanedioic acid

Schedule A; Schedule B

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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)

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Jaime Merchan: lead
• Bristol-Myers Squibb: collaborator
• Pfizer: collaborator

Study Sites (1)

University of Miami Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

MeSH Terms

Interventions

ixabepilone; Sunitinib; Succinic Acid

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Succinates; Dicarboxylic Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals

Study Officials

• Jaime R. Merchan, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: April 18, 2009
• First Posted: April 21, 2009
• Study Start: November 1, 2008
• Primary Completion: November 1, 2013
• Study Completion: July 1, 2015
• Last Updated: October 9, 2015

Record last verified: 2015-07

Locations

US (1)