Single Agent Erlotinib in Chemotherapy-naive Androgen Independent Prostate Cancer

Study Overview
=================
Brief Summary
-----------------
Objectives to evaluate the activity of Erlotinib in prostate cancer patients who are hormone refractory and androgen independent and have not been exposed to chemotherapy.

Detailed Description
-----------------
This is a phase II open label single center study that evaluates the activity, efficacy, and toxicity of single agent Tarceva in chemotherapy-naive AIPC patients. Patients will receive single agent Tarceva at 150 mg daily without interruption until disease progression, unacceptable toxicity, or investigator's discretion. Eligible patients are those with documented prostate cancer (regardless of Gleason Score) who are considered hormone refractory as defined below. All patients must fail an anti-androgen withdrawal trial if they were already on such therapy. If patients were on LHRH analogues alone, they must fail the addition of an anti-androgen before being classified as hormone refractory. All patients must have adequate organ functions as specified below and have an ECOG performance status of 2 or less. It is hypothesized that 25 patients will be needed to adequately assess the activity of Tarceva in AIPC. The activity of Tarceva in other malignancies has been demonstrated with dosed ranging from 100 to 150 mg daily. It is acceptable not to interrupt therapy unless toxicity occurs of disease progression is documented. Starting patients at 150 mg daily seems to be the most logical step, but dose reductions will be implemented based on side effects and adverse events.

Official Title
-----------------
Phase II Study Investigating the Efficacy and Activity of Single Agent Erlotinib in Chemotherapy-Naive Androgen Independent Prostate Cancer

Conditions
-----------------
Prostate Cancer

Intervention / Treatment
-----------------
* Drug: Tarceva


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Documented prostate cancer regardless of Gleason score Patients should be considered hormone refractory and androgen independent. They must fail LHRH analogues, and anti-androgen withdrawal trial. Failure is confirmed by an increase in PSA value of 10% or more than the value immediately before, and confirmed by another assessment 2 weeks later. Patients have to have measurable disease either biochemically using rising PSA or/and with metastatic disease to the bone or visceral organs. Performance status of 2 or less using ECOG scale.· Adequate liver function tests with ALT/AST being < 3x normal, total bilirubin of 1.5 or less, and adequate renal function measured by a creatinine of 2.0 mg/dl or less. Alkaline phosphatase values are never exclusion criteria if it is deemed related to bone metastases. Patients need to have adequate bone marrow function. ANC of 1000 or above, Hgb of 9.0 g/dl or above, and platelets of 100,000 or above. If other causes are affecting plts counts such as autoimmune disorders, patients are allowed on study. Patients with inadequate bone marrow function that is deemed related to bone marrow involvement with prostate cancer are allowed at the investigator's discretion. Patients with other malignancies are allowed as long as there is no evidence of the other malignancy present at entry time, and it has been 3 years or more since the treatment for the other disorder was completed. Patients with prior exposure to investigational therapies including vaccines are allowed on this study as long as their last exposure was 4 weeks prior to study entry.Patients with known bone metastases are allowed to receive intravenous bisphosphonates such as aredia or zometa. Patients on oral bisphosphonates are also allowed. Chemo Naive Exclusion Criteria: Patients with prior exposure to Tarceva Patients who have received any prior systemic chemotherapy for prostate cancer. Exposure to chemotherapy for other malignancies is allowed as long as last chemotherapy was completed 3 years prior to study entry. Patients with prior malignancies are excluded except for those who have non-melanoma skin cancers or other cancers that are in remission with the last therapy given 3 years prior to enrollment. Prior exposure to any form of steroids is allowed and is not considered exclusion criteria. Performance status of 3 or above using ECOG scale. Known HIV positive status Known CNS involvement with prostate cancer
Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tarceva<br>Tarceva 150 mg QD | Drug: Tarceva<br>* 150mg QD<br>* Other names: erlotinib;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Clinical Benefit of Tarceva in CRPC. | Overall Clinical Benefit = percentage of partial responders (PR)+ the percentage of patients with stable disease (SD). Partial Response (PR) is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum. Stable Disease (SD)is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease, using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0). | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | One year survival rate. | during study | 
| Time to Disease Progression | Patients were evaluated for response biochemically and radiographically at each response assessment. RECIST 1.0 criteria were used for radiographic response. PSA measurement at a central laboratory was used to assess biochemical response. Patients must have had a baseline PSA of 5 ng/ml to be evaluated for PSA response. PSA was measured every 8 weeks. For patients with measurable disease radiographically, PSA progression was not considered as having progressive disease. Refer to study publication for details. | 25 months |