Single Agent Erlotinib in Chemotherapy-naive Androgen Independent Prostate Cancer

• Sponsor: Oncology Specialists, S.C. (Other)
• Overall Status: Completed
• CT.gov ID: NCT00272038
• Collaborator: (none)
• Enrollment: 29
• Location: 1
• Arm: 1
• Duration (Months): 58
• Patients Per Site Per Month: 0.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: Tarceva	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 29 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study Investigating the Efficacy and Activity of Single Agent Erlotinib in Chemotherapy-Naive Androgen Independent Prostate Cancer
• Study Start Date: Dec 1, 2005
• Actual Primary Completion Date: Oct 1, 2010
• Actual Study Completion Date: Oct 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tarceva Tarceva 150 mg QD	Drug: Tarceva; 150mg QD; Other Names: erlotinib

Outcome Measures

Primary Outcome Measures

1. Overall Clinical Benefit of Tarceva in CRPC. [5 years]

   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).

Secondary Outcome Measures

1. Overall Survival [during study]

   One year survival rate.

2. Time to Disease Progression [25 months]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Oncology Specialists, SC	Park Ridge	Illinois	United States	60068

Sponsors and Collaborators

• Oncology Specialists, S.C.

Investigators

• Principal Investigator: Chadi Nabhan, MD, Oncology Specialists, SC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Dr. Sigrun Hallmeyer, Sigrun Hallmeyer, MD Director of Research; Chadi Nabhan, MD Principal Investigator, Oncology Specialists, S.C.
• ClinicalTrials.gov Identifier: NCT00272038
• Other Study ID Numbers: OSI3652S (0513); NCT00321841
• First Posted: Jan 4, 2006
• Last Update Posted: Jun 27, 2018
• Last Verified: May 1, 2018

• Additional relevant MeSH terms: Prostatic Neoplasms; Erlotinib Hydrochloride

Study Results

Participant Flow

Recruitment Details	Eligible patients were those who met the criteria of Castration Resistant Prostate Cancer (CRPC)who had not yet received chemotherapy.
Pre-assignment Detail	Patients must have had adquate bone marrow function and, Eastern Cooperative Oncology Group (ECOG) <3, and measurable disease.

Arm/Group Title	Tarceva
Arm/Group Description	Tarceva 150 mg orally every day
Period Title: Overall Study
STARTED	29
COMPLETED	22
NOT COMPLETED	7

Baseline Characteristics

Arm/Group Title	Tarceva
Arm/Group Description	Tarceva 150 mg QD
Overall Participants	29
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	2 6.9%
>=65 years	27 93.1%
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	29 100%
Region of Enrollment (participants) [Number]
United States	29 100%

Outcome Measures

1. Primary Outcome

Title	Overall Clinical Benefit of Tarceva in CRPC.
Description	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).
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tarceva
Arm/Group Description	Tarceva 150 mg QD
Measure Participants	22
Number [percentage of pts w/clinical benefit]	36

2. Secondary Outcome

Title	Overall Survival
Description	One year survival rate.
Time Frame	during study

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tarceva
Arm/Group Description	Tarceva 150 mg QD
Measure Participants	22
Number [% of partcipants alive at one year]	58

3. Secondary Outcome

Title	Time to Disease Progression
Description	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.
Time Frame	25 months

Outcome Measure Data

Analysis Population Description

29 participants enrolled. only 22 were evaluable, 4 withdrew consent, 2 had rapid PSA increase & 1 had cord compression

Arm/Group Title	Tarceva
Arm/Group Description	Tarceva 150 mg QD Tarceva: 150mg QD
Measure Participants	22
Median (Full Range) [months]	2

Adverse Events

Arm/Group Title	Tarceva
Arm/Group Description	Tarceva 150 mg QD
All Cause Mortality
	Tarceva
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Tarceva
	Affected / at Risk (%)	# Events
Total	12/29 (41.4%)
Cardiac disorders
Congestive Heart Failure	1/29 (3.4%)
Gastrointestinal disorders
Gastro Intestinal Bleed	1/29 (3.4%)
Diarrhea	1/29 (3.4%)
Bowel Obstruction	1/29 (3.4%)
General disorders
Weakness	2/29 (6.9%)
Dehydration	2/29 (6.9%)
Decompensation	1/29 (3.4%)
Infections and infestations
Cellulitis	1/29 (3.4%)
Musculoskeletal and connective tissue disorders
Chest Pain	1/29 (3.4%)
Involuntary Movement of Hands and Arms	1/29 (3.4%)
Spinal Cord Compression	1/29 (3.4%)
Renal and urinary disorders
Hematuria	5/29 (17.2%)
Renal Failure	1/29 (3.4%)
Respiratory, thoracic and mediastinal disorders
Shortness of Breath	1/29 (3.4%)
Hypoxia	1/29 (3.4%)
Pneumonia	1/29 (3.4%)
Pulmonary Emboli	1/29 (3.4%)
Other (Not Including Serious) Adverse Events
	Tarceva
	Affected / at Risk (%)	# Events
Total	29/29 (100%)
Blood and lymphatic system disorders
Alkaline Phosphatase High Grade 3 & 4	2/29 (6.9%)
Aspartate Aminotransferase Elevated Grade 1 - 4	2/29 (6.9%)
Anemia Grade 1 & 2	12/29 (41.4%)
Lymphopenia Grade 1 - 4	6/29 (20.7%)
Potassium Decreased Grade 1 & 2	2/29 (6.9%)
Potassium Increased Grade 1 & 2	2/29 (6.9%)
Gastrointestinal disorders
Diarrhea Grade 3 & 4	3/29 (10.3%)
Appetite decreased Grade 1 & 2	15/29 (51.7%)
Calcium Low Grade 1 & 2	6/29 (20.7%)
Constipation Grade 1 & 2	5/29 (17.2%)
Dehydration Grade 1 - 4	5/29 (17.2%)
Diarrhea Grade 1 & 2	22/29 (75.9%)
Gastroesophageal Reflux Disease Grade 1 & 2	4/29 (13.8%)
Hyperglycemia Grade 1 - 4	6/29 (20.7%)
Mouth Sores Grade 1 & 2	7/29 (24.1%)
Mouth Dry Grade 1 & 2	11/29 (37.9%)
Protein Decreased Grade 1 & 2	2/29 (6.9%)
Swallowing Difficulty Grade 1 & 2	2/29 (6.9%)
Sodium Decreased Grade 1 & 2	2/29 (6.9%)
Taste Change Grade 1 & 2	2/29 (6.9%)
General disorders
Fatigue Grade 3 & 4	2/29 (6.9%)
Rash Grade 3 & 4	2/29 (6.9%)
Chest Pain Grade 1 & 2	4/29 (13.8%)
Chills Grade 1 & 2	5/29 (17.2%)
Edema Grade 1 & 2	4/29 (13.8%)
Fatigue Grade 1 - 4	14/29 (48.3%)
Hematuria Grade 1 & 2	5/29 (17.2%)
Hot Flashes Grade 1 & 2	5/29 (17.2%)
Libido decreased Grade 1 & 2	4/29 (13.8%)
Eyes dry Grade 1 & 2	2/29 (6.9%)
Eyes Watery Grade 1 & 2	2/29 (6.9%)
Memory Loss Grade 1 & 2	2/29 (6.9%)
Infections and infestations
Pneumonia Grade 3 & 4	2/29 (6.9%)
Fever Grade 1 & 2	4/29 (13.8%)
Fungal Infection Grade 1 & 2	3/29 (10.3%)
Infection Grade 1 & 2	7/29 (24.1%)
Urinary Tract Infection Grade 1 & 2	2/29 (6.9%)
Nervous system disorders
Arthralgia Grade 1 & 2	9/29 (31%)
Headache Grade 1 & 2	6/29 (20.7%)
Lightheadedness Grade 1 & 2	8/29 (27.6%)
Psychiatric disorders
Depression Grade 1 & 2	10/29 (34.5%)
Insomnia Grade 1 & 2	5/29 (17.2%)
Renal and urinary disorders
Low Creatinine Grade 3 & 4	2/29 (6.9%)
Anxiety Grade 1 & 2	9/29 (31%)
Alkaline Phosphatase Increased Grade 1 & 2	3/29 (10.3%)
Renal Insufficiency Grade 1 - 4	3/29 (10.3%)
Blood Urea Nitrogen increased Grade 1 & 2	2/29 (6.9%)
Creatinine Increased Grade 1 & 2	2/29 (6.9%)
Respiratory, thoracic and mediastinal disorders
Cough Grade 1 & 2	5/29 (17.2%)
Dsynea on Exertion Grade 1 & 2	3/29 (10.3%)
Hemoptesis Grade 1 & 2	3/29 (10.3%)
Wheezing Grade 1 & 2	2/29 (6.9%)
Skin and subcutaneous tissue disorders
Hand Foot Syndrome Grade 1 - 4	3/29 (10.3%)
Hives Grade 1 & 2	5/29 (17.2%)
Itching Grade 1 & 2	7/29 (24.1%)
Nail changes Grade 1 & 2	2/29 (6.9%)
Vascular disorders
Bruises easily	5/29 (17.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.