CP-868,596 And CP-868,596 Plus AG-013736 In Combination With Docetaxel In Advanced Solid Tumors

Phase I Study To Determine The Maximally Tolerated Dose Of Oral, Daily CP-868,596 And CP-868,596 Plus AG-013736 When Given In Combination With Docetaxel Administered Every 3 Weeks To Patients With Advanced Solid Tumors

A5301005 is a phase 1 study in patients with solid tumors which is testing the safety and tolerability of adding targeted agents to a standard chemotherapy. CP-868,596 is a platelet-derived growth factor receptor inhibitor (PDGFR) and AG-13736 is a vascular endothelial growth factor receptor inhibitor (VEGFR). This study will test the use of docetaxel (the standard chemotherapy) with either CP-868,596 or the combination of CP-868,596 and AG-13736.

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: CP-868,596; Drug: Docetaxel; Drug: CP-868,596; Drug: Docetaxel; Drug: AG-013736

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • East Melbourne, Victoria, Australia, 3002
      • Pfizer Investigational Site
• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Pfizer Investigational Site

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

Inclusion Criteria:

• Be ≥18 years old and with histologically or cytologically confirmed advanced solid tumors refractory/resistant to currently available therapies or for which there is no standard therapy.
• Patients with primary brain tumors are not eligible.
• Have at least one site of measurable disease.

Exclusion Criteria:

• Received chemotherapy (including targeted agents such as erlotinib), radiotherapy, immunotherapy or any investigational therapy within 3 weeks of study entry (within 6 weeks for previous treatments with nitrosoureas or mitomycin C).
• Received tamoxifen within 4 weeks prior to study entry.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; 60 mg BID/ 75 mg/m2	Drug: CP-868,596; Oral tablet 60 mg BID continuous; Drug: Docetaxel; Intravenous 75 mg/m2 every three weeks; Drug: CP-868,596; Oral tablet 100 mg BID continuous; Drug: Docetaxel; Intravenous 100 mg/m2 every three weeks
Experimental: Cohort 2; 100 mg BID/75 mg/m2	Drug: CP-868,596; Oral tablet 60 mg BID continuous; Drug: Docetaxel; Intravenous 75 mg/m2 every three weeks; Drug: CP-868,596; Oral tablet 100 mg BID continuous; Drug: Docetaxel; Intravenous 100 mg/m2 every three weeks
Experimental: Cohort 3; 100 mg BID/100 mg/m2	Drug: CP-868,596; Oral tablet 60 mg BID continuous; Drug: Docetaxel; Intravenous 75 mg/m2 every three weeks; Drug: CP-868,596; Oral tablet 100 mg BID continuous; Drug: Docetaxel; Intravenous 100 mg/m2 every three weeks
Experimental: Cohort 4b; CP-868,596 + AG-013736 + TXT 75	Drug: CP-868,596; Oral tablet 60 mg BID continuous; Drug: Docetaxel; Intravenous 75 mg/m2 every three weeks; Drug: CP-868,596; Oral tablet 100 mg BID continuous; Drug: Docetaxel; Intravenous 100 mg/m2 every three weeks; Drug: AG-013736; Oral tablet 5 mg BID continuous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
First-cycle Dose Limiting Toxicities	2.5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Determine the safety and tolerability of the combination of daily CP-868,596 and docetaxel on an every 3-week schedule	2.5 years
Determine the safety and tolerability of the combination of daily CP-868,596 plus daily AG-013736 plus docetaxel on an every 3-week schedule	2.5 years
To evaluate the pharmacokinetics (PK) of CP-868,596 and docetaxel when given in combination	2.5 years
To evaluate the pharmacokinetics (PK) of CP-868,596, AG-013736 and docetaxel when given in combination	2.5 years
Conduct biomarker investigations on plasma/serum samples to explore critical events in pharmacodynamic response to CP-868,596 (eg, VEGF, phospho-SHP, etc.)	2.5 years
To explore the relationship between polymorphisms in genes involved in the metabolism and transport of CP-868,596 and pharmacokinetic/pharmacodynamic parameters	2.5 years
To explore the effects of CP-868,596 on tumor blood flow and permeability via DCE-MRI	2.5 years
To assess any preliminary clinical evidence of anti-tumor activity using RECIST	2.5 years

Collaborators and Investigators

• Sponsor: Arog Pharmaceuticals, Inc.

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: December 1, 2005
• Primary Completion (Actual): June 1, 2008
• Study Completion (Actual): June 1, 2008

Study Registration Dates

• First Submitted: July 24, 2009
• First Submitted That Met QC Criteria: July 28, 2009
• First Posted (Estimate): July 30, 2009

Study Record Updates

• Last Update Posted (Estimate): January 19, 2012
• Last Update Submitted That Met QC Criteria: January 18, 2012
• Last Verified: August 1, 2011

More Information

Terms related to this study

• Keywords: targeted therapy; PDGFr Inhibition;; VEGFr inhibition
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Protein Kinase Inhibitors; Docetaxel; Axitinib; Crenolanib
• Other Study ID Numbers: A5301005