A Study of Imatinib and Docetaxel in Prostate Cancer

• Sponsor: Leonard Appleman (Other)
• Overall Status: Completed
• CT.gov ID: NCT00251225
• Collaborator: Novartis Pharmaceuticals (Industry)
• Enrollment: 49
• Location: 1
• Arm: 1
• Duration (Months): 103
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the effectiveness of two drugs, docetaxel and Gleevec®(also called imatinib), in prostate cancer that no longer responds to hormone therapy. The investigators are interested in finding out if the combination of these two drugs is more effective than docetaxel alone in the treatment of prostate cancer.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: Gleevec; Drug: Docetaxel	Phase 2

Detailed Description

This is a non-randomized multicenter Phase II trial of Gleevec and docetaxel in chemo naïve metastatic hormone refractory prostate cancer. The primary objective of this study is to assess the time to disease progression in patients with hormone refractory prostate cancer treated with daily oral imatinib and intravenous docetaxel, administered every three weeks. Secondary objectives include: 1) to assess the rate of response to imatinib and docetaxel, using Prostate Specific Antigen (PSA) and/or measurable disease; 2) to assess the overall survival of patients with hormone refractory prostate cancer treated with imatinib and docetaxel; and 3) to evaluate the qualitative and quantitative toxicities of this combination.

Study Design

• Study Type: Interventional
• Actual Enrollment: 49 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Imatinib and Docetaxel in Metastatic Hormone Refractory Prostate Cancer
• Study Start Date: Aug 1, 2005
• Actual Primary Completion Date: Mar 1, 2009
• Actual Study Completion Date: Mar 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Hormone Refractory Prostate Cancer Gleevec + Docetaxel: Daily Oral Gleevec in Combination with Every-Three-Week Intravenous Docetaxel	Drug: Gleevec; Imatinib-400mg po qd for 10 days to commence on day 3. On day 0, Docetaxel 60mg/m^2 administered IV; Other Names: Imatinib Imatinib Mesylate ST1571 ; Drug: Docetaxel; 60 mg/m^2 administered IV on day 0; Other Names: Taxotere

Outcome Measures

Primary Outcome Measures

1. Overall Time To Progression (TTP) [Up to 24 months]

   TTP is the amount of time from date of registration to date of first documentation of progression or symptomatic deterioration. For progression, one or more of the following must occur: (1) 20% increase in the sum of longest diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline. (2) Increase in PSA by at least 25% from baseline in patients whose PSA did not decrease, and of 50% from nadir in patients whose PSA decreased with a confirmation 3 weeks later. (3) Unequivocal progression of non-measurable disease in the opinion of the treating physician (an explanation must be provided). (4) Appearance of any new lesion/site. (5) Death due to disease without prior documentation of progression and without symptomatic deterioration, which is defined as global deterioration of health status requiring discontinuation of treatment without objective evidence of progression.

Secondary Outcome Measures

1. Prostate-Specific Antigen (PSA) Response Rate [Up to 12 months]

   PSA response rate is the number of participants who experienced a best response of: complete response, CR (PSA less than or equal to 0.2 ng/mL, documented two or more times, a minimum of four weeks apart), partial response, PR (a decline in PSA by at least 50%, confirmed by a second PSA value four or more weeks later) or stable disease (does not qualify for CR, PR, Progression or Symptomatic Deterioration, at least 6 weeks after registration) / total number of analyzable patients.

2. Overall Survival (OS) [Up to 60 months]

   OS is the amount of time in months from the date of registration to the date of death from any cause.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Must have a histologic diagnosis of adenocarcinoma of the prostate Stage D2 that is unresponsive or refractory to hormone therapy. Must have metastatic prostate cancer with a rising PSA, and deemed to be hormone refractory.

2. All subjects must have pre-study PSA within 28 days prior to registration

3. Subjects who have measurable disease must have had X-rays, scans or physical examinations used for tumor measurement completed within 28 days prior to registration. Subjects must have non-measurable disease assessed within 28 days (for PSA level) or 42 days (for imaging studies) prior to registration.

4. Subjects with bone metastases, as documented by X-ray, bone scan, MRI, or biopsy.

5. All subjects must have had a CT scan of the abdomen and pelvis within 28 days prior to registration.

6. Subjects must have been surgically or medically castrated. If the method of castration was LHRH (Luteinizing Hormone-Releasing Hormone) agonists, then the subject must be willing to continue the use of LHRH agonists.

7. If the subject has been treated with non-steroidal anti-androgens or other hormonal treatment these agents must have been stopped at least 28 days prior to enrollment for flutamide or ketoconazole, and at least 42 days prior to enrollment for bicalutamide or nilutamide; and the subjects must have demonstrated progression of disease since the agents were suspended.

8. Prior radiation therapy is allowed. At least 21 days must have elapsed since the completion of radiation therapy, and the subject must have recovered from the side effects of the radiation

9. 1. Due to the unknown side effects of imatinib, men of reproductive potential must agree to use an effective contraceptive method.

10. Subjects must have recovered from major infections and/or surgical procedures and, in the opinion of the investigator, not have significant active concurrent other medical illness precluding protocol treatment.

11. ECOG performance status of 0-1

12. ANC ≥ 1,500/mL and a platelet count of ³ 100,000/mL. These tests must be obtained within 7 days prior to registration.

13. Serum bilirubin ≤ 1.3, SGOT and SGPT ≤ 2 x institutional upper limit of normal, and a serum creatinine ≤ 1.8 mg/dl. These tests must be obtained within 7 days prior to registration. Testosterone level may be done 28 days prior to study entry. Testosterone level should be below 50 ng/dL.

Exclusion Criteria:

1. No prior chemotherapy for hormone-refractory disease is allowed. At least three weeks must have elapsed since the completion of any non-cytotoxic investigational therapy, and the patient must have recovered from the side effects of the therapy.

2. No other cytotoxics, biological response modifiers, radiation therapy, corticosteroid or hormonal concomitant therapy (other than continuing LHRH treatment) may be given during protocol treatment. Bisphosphonates may be given during protocol treatment. No unconventional therapy may be given during protocol treatment.

3. Subjects must NOT have Grade III/IV cardiac problems as defined by the New York Heart Association Criteria.

4. Subjects with known chronic liver disease are NOT eligible

5. Must NOT have a known diagnosis of human immunodeficiency virus (HIV) infection.

6. Subjects must NOT have known brain metastases.

7. No prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ carcinoma of any site, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hillman Cancer Center	Pittsburgh	Pennsylvania	United States	15232

Sponsors and Collaborators

• Leonard Appleman
• Novartis Pharmaceuticals

Investigators

• Principal Investigator: Leonard J Appleman, MD, University of Pittsburgh Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Leonard Appleman, MD, University of Pittsburgh
• ClinicalTrials.gov Identifier: NCT00251225
• Other Study ID Numbers: 05-019
• First Posted: Nov 9, 2005
• Last Update Posted: Aug 9, 2017
• Last Verified: Jul 1, 2017

• Keywords provided by Leonard Appleman, MD, University of Pittsburgh: prostate
• Additional relevant MeSH terms: Prostatic Neoplasms; Docetaxel; Imatinib Mesylate

Study Results

Participant Flow

Arm/Group Title	Hormone Refractory Prostate Cancer Patients
Arm/Group Description	Patients with hormone refractory prostate cancer treated with Docetaxel 60 mg/m^2 IV every 21 days + Imatinib 400 mg PO daily, or, for 10/21 days
Period Title: Overall Study
STARTED	49
COMPLETED	49
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Hormone Refractory Prostate Cancer Patients
Arm/Group Description	Docetaxel 60 mg/m^2 IV every 21 days + Imatinib 400 mg PO daily, or, for 10/21 days
Overall Participants	49
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	69
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	49 100%

Outcome Measures

1. Primary Outcome

Title	Overall Time To Progression (TTP)
Description	TTP is the amount of time from date of registration to date of first documentation of progression or symptomatic deterioration. For progression, one or more of the following must occur: (1) 20% increase in the sum of longest diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline. (2) Increase in PSA by at least 25% from baseline in patients whose PSA did not decrease, and of 50% from nadir in patients whose PSA decreased with a confirmation 3 weeks later. (3) Unequivocal progression of non-measurable disease in the opinion of the treating physician (an explanation must be provided). (4) Appearance of any new lesion/site. (5) Death due to disease without prior documentation of progression and without symptomatic deterioration, which is defined as global deterioration of health status requiring discontinuation of treatment without objective evidence of progression.
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

Patients with hormone refractory prostate cancer who received at least 1 cycle of Docetaxel + Imatinib

Arm/Group Title	Hormone Refractory Prostate Cancer Patients
Arm/Group Description	Docetaxel 60 mg/m^2 IV every 21 days + Imatinib 400 mg PO daily, or, for 10/21 days
Measure Participants	29
Median (95% Confidence Interval) [months]	6.4

2. Secondary Outcome

Title	Prostate-Specific Antigen (PSA) Response Rate
Description	PSA response rate is the number of participants who experienced a best response of: complete response, CR (PSA less than or equal to 0.2 ng/mL, documented two or more times, a minimum of four weeks apart), partial response, PR (a decline in PSA by at least 50%, confirmed by a second PSA value four or more weeks later) or stable disease (does not qualify for CR, PR, Progression or Symptomatic Deterioration, at least 6 weeks after registration) / total number of analyzable patients.
Time Frame	Up to 12 months

Outcome Measure Data

Analysis Population Description

Patients with hormone refractory prostate cancer who received at least 1 cycle of Docetaxel + Imatinib

Arm/Group Title	Hormone Refractory Prostate Cancer Patients
Arm/Group Description	Docetaxel 60 mg/m^2 IV every 21 days + Imatinib 400 mg PO daily, or, for 10/21 days
Measure Participants	29
Number [percentage of patients]	72.4

3. Secondary Outcome

Title	Overall Survival (OS)
Description	OS is the amount of time in months from the date of registration to the date of death from any cause.
Time Frame	Up to 60 months

Outcome Measure Data

Analysis Population Description

Patients with hormone refractory prostate cancer who received at least 1 cycle of Docetaxel + Imatinib

Arm/Group Title	Hormone Refractory Prostate Cancer Patients
Arm/Group Description	Docetaxel 60 mg/m^2 IV every 21 days + Imatinib 400 mg PO daily, or, for 10/21 days
Measure Participants	29
Median (95% Confidence Interval) [months]	23.1

Adverse Events

Arm/Group Title	Hormone Refractory Prostate Cancer Patients
Arm/Group Description	Patients with hormone refractory prostate cancer treated with Docetaxel 60 mg/m^2 IV every 21 days + Imatinib 400 mg PO daily, or, for 10/21 days
All Cause Mortality
	Hormone Refractory Prostate Cancer Patients
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Hormone Refractory Prostate Cancer Patients
	Affected / at Risk (%)	# Events
Total	35/49 (71.4%)
Blood and lymphatic system disorders
Hemoglobin	3/49 (6.1%)
Leukocytes (total WBC)	4/49 (8.2%)
Neutrophils/granulocytes (ANC/AGC)	11/49 (22.4%)
Cardiac disorders
Cardiac ischemia/infarction	1/49 (2%)
Cardiovascular/Arrhythmia-Other	1/49 (2%)
Cardiovascular/General-Other	1/49 (2%)
Ventricular arrhythmia, Ventricular fibrillation	1/49 (2%)
Gastrointestinal disorders
Nausea	1/49 (2%)
Vomiting	1/49 (2%)
Dehydration	3/49 (6.1%)
General disorders
Fever (in the absence of neutropenia, where neutropenia is defined as AGC<1.0 x 10e9/L)	1/49 (2%)
Heartburn/dyspepsia	1/49 (2%)
Hematochezia	1/49 (2%)
Secondary Malignancy-Other (excludes metastasis from initial primary)	1/49 (2%)
Infections and infestations
Infection - Other (Specify, __)	1/49 (2%)
Infection with normal ANC or Grade 1 or 2 neutrophils, Lung (pneumonia)	1/49 (2%)
Infection/Febrile Neutropenia-Other	1/49 (2%)
Febrile neutropenia (fever of unknown origin)(ANC <1.0 x 10e9/L, fever >=38.5 degrees C)	4/49 (8.2%)
Investigations
Alkaline phosphatase	1/49 (2%)
Calcium, serum-low (hypocalcemia)	1/49 (2%)
Hypocalcemia	1/49 (2%)
Renal and urinary disorders
Obstruction, GU, Ureter	1/49 (2%)
Urinary retention (including neurogenic bladder)	1/49 (2%)
Respiratory, thoracic and mediastinal disorders
Adult Respiratory Distress Syndrome (ARDS)	1/49 (2%)
Hypoxia	1/49 (2%)
Dyspnea (shortness of breath)	3/49 (6.1%)
Vascular disorders
Hemorrhage, GI, Duodenum	1/49 (2%)
Hemorrhage, GI, Upper GI NOS	1/49 (2%)
Hemorrhage/bleeding with grade 3 or 4 thrombocytopenia	1/49 (2%)
Hemorrhage-Other	1/49 (2%)
Other (Not Including Serious) Adverse Events
	Hormone Refractory Prostate Cancer Patients
	Affected / at Risk (%)	# Events
Total	48/49 (98%)
Blood and lymphatic system disorders
Lymphopenia	2/49 (4.1%)
Platelets	4/49 (8.2%)
Neutrophils/granulocytes (ANC/AGC)	14/49 (28.6%)
Hemoglobin	17/49 (34.7%)
Leukocytes (total WBC)	17/49 (34.7%)
Lymphatics - Other (Specify, __)	1/49 (2%)
Edema: head and neck	4/49 (8.2%)
Edema: limb	12/49 (24.5%)
Cardiac disorders
Cardiac Arrhythmia - Other (Specify, __)	1/49 (2%)
Supraventricular and nodal arrhythmia, Atrial flutter	1/49 (2%)
Ventricular arrhythmia, PVCs	1/49 (2%)
Supraventricular and nodal arrhythmia, Sinus tachycardia	3/49 (6.1%)
Left ventricular diastolic dysfunction	1/49 (2%)
Hypertension	3/49 (6.1%)
Hypotension	3/49 (6.1%)
Ear and labyrinth disorders
Otitis, middle ear (non-infectious)	1/49 (2%)
Eye disorders
Ophthalmoplegia/diplopia (double vision)	1/49 (2%)
Vision-flashing lights/floaters	1/49 (2%)
Ocular/Visual - Other (Specify, __)	2/49 (4.1%)
Watery eye (epiphora, tearing)	2/49 (4.1%)
Gastrointestinal disorders
Dysphagia (difficulty swallowing)	1/49 (2%)
Hemorrhoids	1/49 (2%)
Proctitis	1/49 (2%)
Flatulence	2/49 (4.1%)
Dry mouth/salivary gland (xerostomia)	3/49 (6.1%)
Gastrointestinal - Other (Specify, __)	4/49 (8.2%)
Heartburn/dyspepsia	4/49 (8.2%)
Constipation	7/49 (14.3%)
Mucositis/stomatitis (clinical exam), Oral cavity	7/49 (14.3%)
Dehydration	9/49 (18.4%)
Taste alteration (dysgeusia)	10/49 (20.4%)
Vomiting	13/49 (26.5%)
Anorexia	15/49 (30.6%)
Diarrhea	22/49 (44.9%)
Nausea	24/49 (49%)
General disorders
Constitutional Symptoms - Other (Specify, __)	2/49 (4.1%)
Sweating (diaphoresis)	2/49 (4.1%)
Weight loss	3/49 (6.1%)
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)	4/49 (8.2%)
Rigors/chills	4/49 (8.2%)
Insomnia	7/49 (14.3%)
Fatigue (asthenia, lethargy, malaise)	35/49 (71.4%)
Pain, Neck	1/49 (2%)
Pain - Other (Specify, __)	2/49 (4.1%)
Pain, Abdomen NOS	2/49 (4.1%)
Pain, Joint	2/49 (4.1%)
Pain, Chest/thorax NOS	3/49 (6.1%)
Pain, Muscle	3/49 (6.1%)
Pain, Bone	4/49 (8.2%)
Pain, Head/headache	4/49 (8.2%)
Pain, Extremity-limb	5/49 (10.2%)
Pain, Back	9/49 (18.4%)
Immune system disorders
Allergic reaction/hypersensitivity (including drug fever)	1/49 (2%)
Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)	2/49 (4.1%)
Infections and infestations
Infection (documented)w Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L) Liver	1/49 (2%)
Infection (documented) w Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L), Urinary tract NOS	1/49 (2%)
Infection with normal ANC or Grade 1 or 2 neutrophils, Upper airway NOS	1/49 (2%)
Infection with unknown ANC, Upper airway NOS	1/49 (2%)
Infection - Other (Specify, __)	2/49 (4.1%)
Infection with normal ANC or Grade 1 or 2 neutrophils, Urinary tract NOS	3/49 (6.1%)
Investigations
Albumin, serum-low (hypoalbuminemia)	1/49 (2%)
Glucose, serum-low (hypoglycemia)	1/49 (2%)
Calcium, serum-low (hypocalcemia)	2/49 (4.1%)
Potassium, serum-low (hypokalemia)	3/49 (6.1%)
Alkaline phosphatase	4/49 (8.2%)
Glucose, serum-high (hyperglycemia)	6/49 (12.2%)
Musculoskeletal and connective tissue disorders
Arthritis (non-septic)	1/49 (2%)
Musculoskeletal/Soft Tissue - Other (Specify, __)	1/49 (2%)
Muscle weakness, generalized or specific area (not due to neuropathy), Whole body/generalized	3/49 (6.1%)
Nervous system disorders
Confusion	1/49 (2%)
Extrapyramidal/involuntary movement/restlessness	1/49 (2%)
Mood alteration, Depression	1/49 (2%)
Dizziness	6/49 (12.2%)
Neurology - Other (Specify, __)	7/49 (14.3%)
Neuropathy: sensory	11/49 (22.4%)
Renal and urinary disorders
Urinary retention (including neurogenic bladder)	1/49 (2%)
Urine color change	1/49 (2%)
Urinary frequency/urgency	2/49 (4.1%)
Renal/Genitourinary - Other (Specify, __)	3/49 (6.1%)
Respiratory, thoracic and mediastinal disorders
Hiccoughs (hiccups, singultus)	1/49 (2%)
Hypoxia	1/49 (2%)
Pneumonitis/pulmonary infiltrates	1/49 (2%)
Voice changes/dysarthria (e.g., hoarseness, loss or alteration in voice, laryngitis)	1/49 (2%)
Pulmonary/Upper Respiratory - Other (Specify, __)	2/49 (4.1%)
Dyspnea (shortness of breath)	6/49 (12.2%)
Cough	10/49 (20.4%)
Skin and subcutaneous tissue disorders
Dermatology/Skin - Other (Specify, __)	1/49 (2%)
Hyperpigmentation	1/49 (2%)
Photosensitivity	1/49 (2%)
Pruritus/itching	1/49 (2%)
Rash: acne/acneiform	1/49 (2%)
Wound complication, non-infectious	1/49 (2%)
Injection site reaction/extravasation changes	2/49 (4.1%)
Dry skin	3/49 (6.1%)
Flushing	3/49 (6.1%)
Nail changes	6/49 (12.2%)
Rash/desquamation	9/49 (18.4%)
Hair loss/alopecia (scalp or body)	10/49 (20.4%)
Vascular disorders
Hemorrhage, GI, Lower GI NOS	2/49 (4.1%)
Hemorrhage, GI, Rectum	2/49 (4.1%)

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.