Clinical trial NCT00147550: MEK Inhibitor PD-325901 To Treat Advanced Breast Cancer, Colon Cancer, And Melanoma.
Official title: A Multicenter, Open-Label, Noncomparative Phase 1-2 Clinical And Pharmacokinetic Study Of Oral PD 0325901 In Patients With Advanced Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Melanoma
Colonic Neoplasms
Breast Neoplasms
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2005-09-07
Enrollment: 79
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Objective Response Rate, Safety.
timeFrame: duration of trial
Secondary outcomes:
measure: Time to progression, overall survival, patient reported outcomes.
timeFrame: duration of trial
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Pfizer Investigational Site
state: Alabama
city: Birmingham
country: United States
facility: Pfizer Investigational Site
state: Alabama
city: Birmingham
country: United States
facility: Pfizer Investigational Site
state: Alabama
city: La Jolla
country: United States
facility: Pfizer Investigational Site
state: California
city: La Jolla
country: United States
facility: Pfizer Investigational Site
state: California
city: La Mesa
country: United States
facility: Pfizer Investigational Site
state: California
city: Los Angeles
country: United States
facility: Pfizer Investigational Site
state: California
city: San Diego
country: United States
facility: Pfizer Investigational Site
state: California
city: San Diego
country: United States
facility: Pfizer Investigational Site
state: California
city: Santa Monica
country: United States
facility: Pfizer Investigational Site
state: California
city: Tampa
country: United States
facility: Pfizer Investigational Site
state: Florida
city: Detroit
country: United States
facility: Pfizer Investigational Site
state: Michigan
city: Detroit
country: United States
facility: Pfizer Investigational Site
state: Michigan
city: Rochester
country: United States
facility: Pfizer Investigational Site
state: Minnesota
city: New York
country: United States
facility: Pfizer Investigational Site
state: New York
city: New York
country: United States
facility: Pfizer Investigational Site
state: New York
city: Cleveland
country: United States
facility: Pfizer Investigational Site
state: Ohio
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: 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.