Carboplatin and Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Patients With Advanced or Metastatic Solid Tumors

A Phase I Trial of Carboplatin and Abraxane in Patients With Solid Tumors

RATIONALE: Drugs used in chemotherapy such as paclitaxel albumin-stabilized nanoparticle formulation and carboplatin work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving paclitaxel albumin-stabilized nanoparticle formulation together with carboplatin may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects, the best way to give, and the best dose of paclitaxel albumin-stabilized nanoparticle formulation when given together with carboplatin in treating patients with advanced or metastatic solid tumors.

Study Overview

• Status: Completed
• Conditions: Unspecified Adult Solid Tumor, Protocol Specific
• Intervention / Treatment: Drug: Carboplatin; Drug: Abraxane; Drug: Abraxane; Drug: Abraxane

Detailed Description

OBJECTIVES:

Primary

• Determine the maximum tolerated dose (MTD) of paclitaxel albumin-stabilized nanoparticle formulation given once weekly for 3 weeks when administered with carboplatin given once every 4 weeks.
• Determine the MTD of paclitaxel albumin-stabilized nanoparticle formulation given once every 3 weeks when administered with carboplatin given once every 3 weeks.
• Determine the MTD of paclitaxel albumin-stabilized nanoparticle formulation given in weeks 1 and 2 when administered with carboplatin given once every 3 weeks.
• Evaluate sequence-dependent effects on toxicity and pharmacokinetics in the combination of paclitaxel albumin-stabilized nanoparticle formulation and carboplatin.

Secondary

• Explore the antitumor activity of paclitaxel albumin-stabilized nanoparticle formulation given once weekly or once every 3 weeks.

OUTLINE: Patients are assigned to 1 of 3 treatment arms.

• Arm I: Patients receive carboplatin IV over 30 minutes on day 1 and paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive carboplatin IV over 30 minutes on day 1 and paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
• Arm III: Patients receive carboplatin IV over 30 minutes on day 1 and paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients in arms I and II undergo blood sample collection periodically for pharmacokinetic studies.

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

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

Inclusion criteria:

• Histologically or cytologically confirmed solid tumor

  • Advanced or metastatic disease
• Measurable or evaluable disease

• Must meet 1 of the following criteria:

  • Failed a standard therapy
  • Not a candidate for standard therapy
  • Have a disease for which there is no defined standard therapy

Exclusion criteria:

• Symptomatic brain metastases

PATIENT CHARACTERISTICS:

Inclusion criteria:

• ECOG performance status 0-2
• Life expectancy ≥ 8 weeks
• Absolute neutrophil count > 1,500/mm^3
• Platelet count > 100,000/mm^3
• Hemoglobin > 8.0 g/dL
• Total bilirubin normal
• Serum creatinine normal OR creatinine clearance ≥ 60 mL/min
• AST and ALT ≤ 2.5 x upper limit of normal
• Negative pregnancy test

Exclusion criteria:

• Pregnant or lactating
• Prior anaphylactic reaction or severe allergic reaction to paclitaxel and/or docetaxel
• Active infection that requires treatment with antibiotics for > 4 weeks
• Uncontrolled congestive heart failure
• Symptomatic coronary artery disease or heart block
• Myocardial infarction within the past 3 months
• Peripheral neuropathy ≥ grade 2 from any cause

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy, radiotherapy, or any other therapy for malignancy within the past 3 weeks
• No concurrent filgrastim, pegfilgrastim, or sargramostim during the first course of therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Weekly Arm; Carboplatin day 1, abraxane days 1, 8, 15 every 28 day cycle	Drug: Carboplatin; standard dose of area under the curve (AUC) AUC of 6 in all arms; Other Names: Paraplatin; Drug: Abraxane; 75mg/m2 - 150 mg/m2 given on days 1, 8, 15 of every 28 day cycle; Other Names: Paclitaxil; Drug: Abraxane; 180mg/m2 - 340mg/m2, repeated every 21 days; Other Names: Paclitaxil; Drug: Abraxane; 100mg/m2 - 175/mg/m2 given on days 1, 8 of every 21 day cycle; Other Names: Paclitaxil
Experimental: Every 3 week Arm; Carboplatin day 1, abraxane day 1, every 21 day cycle	Drug: Carboplatin; standard dose of area under the curve (AUC) AUC of 6 in all arms; Other Names: Paraplatin; Drug: Abraxane; 75mg/m2 - 150 mg/m2 given on days 1, 8, 15 of every 28 day cycle; Other Names: Paclitaxil; Drug: Abraxane; 180mg/m2 - 340mg/m2, repeated every 21 days; Other Names: Paclitaxil; Drug: Abraxane; 100mg/m2 - 175/mg/m2 given on days 1, 8 of every 21 day cycle; Other Names: Paclitaxil
Experimental: Arm C; Carboplatin day 1, abraxane day 1, 8 every 21 day cycle	Drug: Carboplatin; standard dose of area under the curve (AUC) AUC of 6 in all arms; Other Names: Paraplatin; Drug: Abraxane; 75mg/m2 - 150 mg/m2 given on days 1, 8, 15 of every 28 day cycle; Other Names: Paclitaxil; Drug: Abraxane; 180mg/m2 - 340mg/m2, repeated every 21 days; Other Names: Paclitaxil; Drug: Abraxane; 100mg/m2 - 175/mg/m2 given on days 1, 8 of every 21 day cycle; Other Names: Paclitaxil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Tolerated Dose (MTD) of Abraxane	To determine the maximum tolerated dose (MTD) of Abraxane weekly days 1, 8, 15 with a carboplatin dose of AUC=6 given on day 1 of a 28 day cycle	28 days
Maximum Tolerated Dose (MTD) of Abraxane given with Carboplatin	To determine the MTD of Abraxane given every 3 weeks with carboplatin given on day 1 of a 21 day cycle	21 days
Sequence-dependent toxicity	To determine if there is any correlation to toxicity based on the order Abraxane and carboplatin are adminstered	28 days

Collaborators and Investigators

• Sponsor: UNC Lineberger Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: December 1, 2004
• Primary Completion (Actual): May 1, 2006
• Study Completion (Actual): September 1, 2007

Study Registration Dates

• First Submitted: August 21, 2007
• First Submitted That Met QC Criteria: August 21, 2007
• First Posted (Estimate): August 23, 2007

Study Record Updates

• Last Update Posted (Estimate): March 6, 2012
• Last Update Submitted That Met QC Criteria: March 5, 2012
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Keywords: unspecified adult solid tumor, protocol specific
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Carboplatin; Paclitaxel; Albumin-Bound Paclitaxel
• Other Study ID Numbers: LCCC0412; CDR0000561620 (Other Identifier: PDQ number)