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

Sponsor

Pfizer (Industry)

Overall Status

Terminated

CT.gov ID

NCT00147550

Collaborator

(none)

Enrollment

Locations

Arm

113

Duration (Months)

4.6

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Melanoma Colonic Neoplasms Breast Neoplasms	Drug: PD-0325901	Phase 1/Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

79 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Feb 1, 2004

Actual Primary Completion Date :

May 1, 2007

Actual Study Completion Date :

Jul 1, 2013

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Objective Response Rate, Safety. [duration of trial]

Secondary Outcome Measures

Time to progression, overall survival, patient reported outcomes. [duration of trial]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Birmingham	Alabama	United States	35233-2115
2	Pfizer Investigational Site	Birmingham	Alabama	United States	35233
3	Pfizer Investigational Site	Birmingham	Alabama	United States	35294
4	Pfizer Investigational Site	La Jolla	California	United States	92037
5	Pfizer Investigational Site	La Jolla	California	United States	92093
6	Pfizer Investigational Site	La Mesa	California	United States	91942
7	Pfizer Investigational Site	Los Angeles	California	United States	90025
8	Pfizer Investigational Site	San Diego	California	United States	92103
9	Pfizer Investigational Site	San Diego	California	United States	92123
10	Pfizer Investigational Site	Santa Monica	California	United States	90404
11	Pfizer Investigational Site	Tampa	Florida	United States	33612
12	Pfizer Investigational Site	Detroit	Michigan	United States	48201
13	Pfizer Investigational Site	Detroit	Michigan	United States	48202
14	Pfizer Investigational Site	Rochester	Minnesota	United States	55905
15	Pfizer Investigational Site	New York	New York	United States	10021
16	Pfizer Investigational Site	New York	New York	United States	10022
17	Pfizer Investigational Site	Cleveland	Ohio	United States	44106