MP470 and Chemotherapy in Treating Patients With Cancer - Full Text View

Sponsor:	SuperGen
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00602875

Purpose

RATIONALE: MP470 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving MP470 together with chemotherapy may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of MP470 when given together with chemotherapy in treating patients with cancer.

Condition	Intervention	Phase
Unspecified Adult Solid Tumor, Protocol Specific	Drug: carboplatin Drug: docetaxel Drug: erlotinib hydrochloride Drug: etoposide Drug: multitargeted receptor tyrosine kinase inhibitor MP470 Drug: paclitaxel Drug: topotecan hydrochloride	Phase I

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	Safety and Dose Finding Study of Oral MP470, a Multi-Targeted Tyrosine Kinase Inhibitor, in Combination With Standard-of-Care Chemotherapy Regimens

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Tyrosine Paclitaxel Etoposide Carboplatin Docetaxel Etoposide phosphate Topotecan hydrochloride Topotecan Erlotinib hydrochloride Erlotinib

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Safety as assessed by patient-reported and investigator-observed adverse events, clinical laboratory tests (i.e., hematology, metabolic profile, and urinalysis), ECGs, echocardiograms or MUGA scans, and physical examination [ Designated as safety issue: Yes ]
Response to treatment as assessed by RECIST criteria [ Designated as safety issue: No ]
Effects of MP470 on pharmacokinetics of standard of care (SOC) agents as assessed by SOC concentrations in plasma before and after dosing with MP470 [ Designated as safety issue: No ]
Pharmacodynamic marker (Rad51 expression in skin biopsies) [ Designated as safety issue: No ]

Estimated Enrollment:	105
Study Start Date:	December 2007
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Regimen I: Experimental Patients receive paclitaxel IV over 3 hours and carboplatin IV over 1 hour on day 1. Patients also receive oral MP470 once daily on days 2-21 of course 1 and on days 1-21 of all subsequent courses.	Drug: multitargeted receptor tyrosine kinase inhibitor MP470 Given orally Drug: paclitaxel Given IV
Regimen II: Experimental Patients receive carboplatin IV over 1 hour on day 1 and etoposide IV over 2 hours on days 1-3. Patients also receive MP470 as in regimen I.	Drug: carboplatin Given IV Drug: etoposide Given IV Drug: multitargeted receptor tyrosine kinase inhibitor MP470 Given orally
Regimen III: Experimental Patients receive topotecan hydrochloride IV over 30 minutes on days 1-5. Patients also receive MP470 as in regimen I.	Drug: multitargeted receptor tyrosine kinase inhibitor MP470 Given orally Drug: topotecan hydrochloride Given IV
Regimen IV: Experimental Patients receive docetaxel IV over 1 hour on day 1. Patients also receive MP470 as in regimen I.	Drug: docetaxel Given IV Drug: multitargeted receptor tyrosine kinase inhibitor MP470 Given orally
Regimen V: Experimental Patients receive oral erlotinib hydrochloride once daily on days 1-21. Patients also receive oral MP470 once daily on days 16-21 of course 1 and on days 1-21 of all subsequent courses.	Drug: erlotinib hydrochloride Given orally Drug: multitargeted receptor tyrosine kinase inhibitor MP470 Given orally

Detailed Description:

OBJECTIVES:

Primary

To estimate the maximum tolerated dose of MP470 when administered in combination with standard of care (SOC) therapy in patients with malignant disease.
To define safety profiles of specific MP470 and SOC therapy combinations in these patients.

Secondary

To estimate therapeutic response rates in patients treated with these regimens.
To quantify the effect of MP470 on the pharmacokinetics of SOC agents.
To collect pharmacodynamic information.

OUTLINE: This is a multicenter, dose-escalation study of MP470. Patients are assigned to 1 of 5 treatment regimens.

Regimen I: Patients receive paclitaxel IV over 3 hours and carboplatin IV over 1 hour on day 1. Patients also receive oral MP470 once daily on days 2-21 of course 1 and on days 1-21 of all subsequent courses.
Regimen II: Patients receive carboplatin IV over 1 hour on day 1 and etoposide IV over 2 hours on days 1-3. Patients also receive MP470 as in regimen I.
Regimen III: Patients receive topotecan hydrochloride IV over 30 minutes on days 1-5. Patients also receive MP470 as in regimen I.
Regimen IV: Patients receive docetaxel IV over 1 hour on day 1. Patients also receive MP470 as in regimen I.
Regimen V: Patients receive oral erlotinib hydrochloride once daily on days 1-21. Patients also receive oral MP470 once daily on days 16-21 of course 1 and on days 1-21 of all subsequent courses.

In all arms, treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Patients undergo blood sample collection during courses 1 and 2 for pharmacokinetic studies. Patients also undergo skin punch biopsy periodically to assess Rad51 expression.

After completion of study treatment, patients are followed for 30 days.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Malignant disease appropriate for initiating treatment with carboplatin/paclitaxel, carboplatin/etoposide, topotecan hydrochloride, docetaxel, or erlotinib hydrochloride
No active CNS metastases
- Prior CNS metastases allowed provided the metastases are stable

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Hemoglobin ≥ 9 g/dL
ANC ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
Total serum bilirubin ≤ 2 mg/dL
AST and ALT ≤ 2.5 times upper limit of normal (ULN) (≤ 5 times ULN if due to hepatic metastases)
Serum creatinine ≤ 2 mg/dL
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 3 months after completion of study therapy
Willing and able to swallow MP470 capsules
Must have normal cardiac function, in the opinion of the investigator, as demonstrated by the following:
- LVEF ≥ 50% on screening echocardiogram or MUGA
- No significant abnormalities on screening ECG (e.g., left bundle branch block, third degree atrioventricular block, acute myocardial infarction, or QTc interval > 450 msec)
- No history of additional risk factors for torsades de pointes (e.g., heart failure, hypokalemia, or family history of long QT syndrome)
No known allergy to MP470 or SOC therapy
No life-threatening illness (other than the malignant disease), medical condition, or organ system dysfunction that, in the opinion of the investigator, could compromise the patient's safety, interfere with the absorption or metabolism of oral MP470, or put the study outcomes at risk
No serious, uncontrolled active infection that requires systemic treatment
No known HIV, HCV, or HBV infection
No significant cardiovascular disease, such as uncontrolled or symptomatic arrhythmias, congestive heart failure, and/or myocardial infarction within the past 12 months

PRIOR CONCURRENT THERAPY:

Recovered from prior anticancer therapy
- No toxicity ≥ grade 2 (other than alopecia)
At least 4 weeks since prior major surgery and recovered
No prior MP470
More than 3 weeks since prior anticancer agents, including investigational agents, immunotherapy, biologic therapy, or hormonal therapy (other than luteinizing hormone-releasing hormone agonists)
More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
More than 4 weeks since prior radiotherapy
No concurrent immunosuppressive agents other than corticosteroids appropriate for standard of care (SOC) therapy or those that have been at stable doses for at least 2 weeks
No concurrent radiotherapy
No other concurrent anticancer therapy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00602875

Locations

United States, Arizona
Premiere Oncology of Arizona	Recruiting
Scottsdale, Arizona, United States, 85260
Contact: Michael S. Gordon, MD 480-860-5000
United States, California
Premiere Oncology	Recruiting
Santa Monica, California, United States, 90404
Contact: Lee S. Rosen, MD 310-633-8400 lrosen@premiereoncology.com
United States, Texas
Cancer Therapy and Research Center	Recruiting
San Antonio, Texas, United States, 78229
Contact: Clinical Trials Office - Cancer Therapy and Research Center 210-616-5798
South Texas Accelerated Research Therapeutics	Recruiting
San Antonio, Texas, United States, 78229
Contact: Anthony W. Tolcher, MD 210-593-5255

Sponsors and Collaborators

SuperGen

Investigators

Study Chair:

Gregory Berk, MD

SuperGen

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000583053, SUPERGEN-SGI-0470-02
Study First Received:	January 25, 2008
Last Updated:	September 22, 2008
ClinicalTrials.gov Identifier:	NCT00602875 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:

Erlotinib
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Mitosis Modulators
Enzyme Inhibitors
Carboplatin
Antimitotic Agents
Protein Kinase Inhibitors

Pharmacologic Actions
Docetaxel
Paclitaxel
Therapeutic Uses
Tubulin Modulators
Topotecan
Etoposide
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on February 08, 2010