MEK Inhibitor PD-325901 To Treat Advanced Breast Cancer, Colon Cancer, And Melanoma.

A Multicenter, Open-Label, Noncomparative Phase 1-2 Clinical And Pharmacokinetic Study Of Oral PD 0325901 In Patients With Advanced Cancer

MEK is a critical member of the MAPK pathway involved in growth and survival of cancer cells. PD-325901 is a new drug designed to block this pathway and kill cancer cells. The purpose of this study is to study the effectiveness of PD-325901 in patients with colon cancer, breast cancer, and melanoma. PD-325901 will be given by mouth as a pill twice a day, CT scans will be done and biopsies will be taken of a tumor before and once during treatment to measure the effects of the drug. Blood samples will be taken to measure the amount of drug in the blood.

Study Overview

• Status: Terminated
• Conditions: Melanoma; Breast Neoplasms; Colonic Neoplasms
• Intervention / Treatment: Drug: PD-0325901

Detailed Description

The study prematurely discontinued on March 15, 2007 due to a safety concern, specifically ocular and neurological toxicity presented at 10 mg twice-a-day and higher doses.

• Study Type: Interventional
• Enrollment (Actual): 79
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Pfizer Investigational Site
    • Birmingham, Alabama, United States, 35294
      • Pfizer Investigational Site
    • Birmingham, Alabama, United States, 35233-2115
      • Pfizer Investigational Site
  • California
    • La Jolla, California, United States, 92037
      • Pfizer Investigational Site
    • La Jolla, California, United States, 92093
      • Pfizer Investigational Site
    • La Mesa, California, United States, 91942
      • Pfizer Investigational Site
    • Los Angeles, California, United States, 90025
      • Pfizer Investigational Site
    • San Diego, California, United States, 92103
      • Pfizer Investigational Site
    • San Diego, California, United States, 92123
      • Pfizer Investigational Site
    • Santa Monica, California, United States, 90404
      • Pfizer Investigational Site
  • Florida
    • Tampa, Florida, United States, 33612
      • Pfizer Investigational Site
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Pfizer Investigational Site
    • Detroit, Michigan, United States, 48201
      • Pfizer Investigational Site
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Pfizer Investigational Site
  • New York
    • New York, New York, United States, 10021
      • Pfizer Investigational Site
    • New York, New York, United States, 10022
      • Pfizer Investigational Site
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • 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:

• Age >= 18 years old
• Tumor accessible for biopsy and willingness to undergo baseline and 1 post treatment biopsy
• Biopsiable, histologically or cytologically confirmed metastatic or inoperable breast cancer, colon cancer, or melanoma. Prior treatment requirement : i) no more than 2 prior cytotoxic chemotherapy regimens for metastatic disease for patients with breast or colon cancers; ii) No prio cytotoxic therapy for patients with melanoma, or iii) measurable lesion (s) that have not been irradiated.
• Adequate renal, liver, and bone marrow function, determined within 2 weeks prior to the first treatment, defined as the following: Serum creatinine <1.5 x ULN, total bilirubin <2 x ULN, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) <3 x ULN (<5 x ULN for patients with liver involvement); absolute neutrophil count (ANC) >1500/ul; and platelet >100,000/ul
• Hemoglobin >9.0 g/dL. Treatment with transfusions or erythropoietin to elevate the hemoglobin level for eligibility purposes is not permitted. Patients must have discontinued erythropoietin at least 2 weeks prior to the first dose of study medication
• Serum calcium <1 x ULN and phosphorus <1 x ULN
• Patients having reproductive potential must use adequate method of birth control. Patients may not be pregnant or breastfeeding.
• ECOG Status of 0,1, or 2.
• Must be able to swallow intact study medication and have no gastrointestinal disorders that may affect absorption of the drug
• Must be able to follow instructions or protocol specified procedures, or have a daily care giver who will be responsible for administering study medication.
• Must be able to give written informed consent.

Exclusion Criteria:

• No parathyroid disorder or history of malignancy associated hypercalcemia
• No ongoing radiation therapy or radio-cytotoxic therapy within prior 4 weeks; No immunotherapy, biologic therapy, hormonal, or molecular targeted therapy within prior 2 weeks
• No concurrent serious infection or life-threatening illness (unrelated to tumor)
• No history of any cancer other than the present condition (except nonmelanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission and off all therapy for that disease for a minimum of 3 years
• No untreated brain metastases.

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

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: PD-0325901; Administered orally either once or twice a day; several dosing schedules evaluated; current dosing schedule is 5 days on-drug, 2-days off drug for 3 weeks in a 28-day cycle. Doses evaluated ranged from 1 mg once a day to 30 mg twice daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Objective Response Rate, Safety.	duration of trial

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to progression, overall survival, patient reported outcomes.	duration of trial

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Boasberg PD, Redfern CH, Daniels GA, Bodkin D, Garrett CR, Ricart AD. Pilot study of PD-0325901 in previously treated patients with advanced melanoma, breast cancer, and colon cancer. Cancer Chemother Pharmacol. 2011 Aug;68(2):547-52. doi: 10.1007/s00280-011-1620-1. Epub 2011 Apr 24.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start: February 1, 2004
• Primary Completion (Actual): May 1, 2007
• Study Completion (Actual): July 1, 2013

Study Registration Dates

• First Submitted: September 2, 2005
• First Submitted That Met QC Criteria: September 2, 2005
• First Posted (Estimate): September 7, 2005

Study Record Updates

• Last Update Posted (Estimate): September 13, 2013
• Last Update Submitted That Met QC Criteria: September 11, 2013
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Skin Diseases; Neoplasms by Histologic Type; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Breast Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Colorectal Neoplasms; Neuroendocrine Tumors; Nevi and Melanomas; Neoplasms; Breast Neoplasms; Melanoma; Colonic Neoplasms
• Other Study ID Numbers: A4581001