Thalidomide and Doxil® in Patients With Androgen Independent Prostate Cancer (AIPC)

• Sponsor: University of Pittsburgh (Other)
• Overall Status: Completed
• CT.gov ID: NCT00307294
• Collaborator: Ortho Biotech, Inc. (Industry)
• Enrollment: 40
• Location: 1
• Arm: 1
• Duration (Months): 70
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

The primary objective of this study is to evaluate PSA response rates of the combination of Doxil and Thalidomide in patients with AIPC who have failed chemotherapy. Secondary objectives include: 1) To evaluate the clinical response rate of this combination on measurable disease 2) To evaluate overall survival for this combination.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: Thalidomide; Drug: Doxil	Phase 2

Detailed Description

This is an open label, Phase II trial of thalidomide and Doxil in patients with androgen independent prostate cancer whom have a rising PSA while on chemotherapy. The primary objective of this study is to evaluate PSA response rates of the combination of Doxil and

Thalidomide in patients with AIPC who have failed chemotherapy. Secondary objectives include:

1. To evaluate the clinical response rate of this combination on measurable disease (If measurable soft tissue lesions are present on radiological or clinical exam) ; 2) To evaluate overall survival for this combination. There will be between 18 and 35 subjects at least 18 years of age enrolled on this single site study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Thalidomide and Doxil® (Doxorubicin HCL Liposome Injection) in Patients With Androgen Independent Prostate Cancer (AIPC) With a Rising PSA While on Chemotherapy
• Study Start Date: Mar 1, 2006
• Actual Primary Completion Date: Jan 1, 2012
• Actual Study Completion Date: Jan 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: thalidomide and doxil Combination of Thalidomide and Doxil	Drug: Thalidomide; 100 mg PO q day and escalation will occur bt 50 mg every 4 weeks to a maximum of 200mg; Other Names: Thalomid ; Drug: Doxil; On day 1 of each cycle 40 mg/m2 IV over 1 hr every 28 days; Other Names: doxorubicin liposome

Outcome Measures

Primary Outcome Measures

1. Response Rate [24 weeks]

   The number of patients experiencing a response to treatment, per RECIST criteria / total number of patients evaluable for response.

Secondary Outcome Measures

1. Best Overall PSA Response [4 weeks]

   PSA response as stable disease or progressive disease, per Prostate-Specific Antigen Working Group criteria.

2. Overall Survival [36 months]

3. Time to Progression [Up to 18 months]

   Time from start of treatment until the disease progression per RECIST criteria.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically or cytologically confirmed adenocarcinoma of the prostate.

• Confirmed androgen independent prostate cancer with evidence of rising PSA (two successive increases in PSA, at least 4 weeks apart) while on chemotherapy. If the PSA is less than 5, the increase in PSA must be at least 50%. Must also have castrate testosterone levels (<50 ng/ml)

• Patients could not have received more than 2 previous chemotherapy regimens.

• No anthracyclines within the past 6 months.

• No prior single agent thalidomide in the last 12 months. No prior cytotoxic chemotherapy + thalidomide given in conjunction

• Age > 18 years of age

• Performance status ECOG 0-2

• Peripheral neuropathy must be < grade 1

• Must have adequate hematologic, hepatic and renal function

• Men of reproductive potential must be willing to consent to using effective contraception while on treatment and for at least 4 weeks thereafter

• Patients must have left ventricular ejection fraction of > 50% within 42 days prior to first dose of study drug. The method used at baseline must be used for later monitoring

• Must have been off an anti-androgen for at least 4-6 weeks (Flutamide and Bicalutamide respectively) and documented as having a rising PSA

• Measurable or evaluable disease (PSA elevation will constitute evaluable disease). Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques CT scan or as >10 mm with spiral CT scan. See section 6.B for the evaluation of measurable disease

• Life expectancy of greater than 3 months

• Patients must be willing and able to comply with the FDA-mandated S.T.E.P.S.® program

• Ability to understand and sign written informed consent approved by the Institutional Review Board [IRB/Ethics Committee], which will be obtained prior to study entry.

Exclusion Criteria:

• Patients with unstable angina, uncompensated CHF, a history of an MI, PE or DVT within the last 3 months

Contacts and Locations

Locations

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

Sponsors and Collaborators

• University of Pittsburgh
• Ortho Biotech, Inc.

Investigators

• Principal Investigator: Gurkamal S Chatta, MD, University of Pittsburgh

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Pittsburgh
• ClinicalTrials.gov Identifier: NCT00307294
• Other Study ID Numbers: 05-078
• First Posted: Mar 27, 2006
• Last Update Posted: Nov 24, 2017
• Last Verified: Jan 1, 2016

• Keywords provided by University of Pittsburgh: Prostate; Androgen; AIPC; Doxil
• Additional relevant MeSH terms: Prostatic Neoplasms; Thalidomide; Doxorubicin

Study Results

Participant Flow

Arm/Group Title	Thalidomide and Doxil
Arm/Group Description	Combination of Thalidomide and Doxil Thalidomide: 100 mg PO q day and escalation will occur bt 50 mg every 4 weeks to a maximum of 200mg Doxil: On day 1 of each cycle 40 mg/m2 IV over 1 hr every 28 days
Period Title: Overall Study
STARTED	40
COMPLETED	39
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Thalidomide and Doxil
Arm/Group Description	Combination of Thalidomide and Doxil Thalidomide: 100 mg PO q day and escalation will occur bt 50 mg every 4 weeks to a maximum of 200mg Doxil: On day 1 of each cycle 40 mg/m2 IV over 1 hr every 28 days
Overall Participants	39
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	70
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	39 100%

Outcome Measures

1. Primary Outcome

Title	Response Rate
Description	The number of patients experiencing a response to treatment, per RECIST criteria / total number of patients evaluable for response.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

Patients that received greater than one cycle of therapy.

Arm/Group Title	Thalidomide and Doxil
Arm/Group Description	Combination of Thalidomide and Doxil Thalidomide: 100 mg PO q day and escalation will occur bt 50 mg every 4 weeks to a maximum of 200mg Doxil: On day 1 of each cycle 40 mg/m2 IV over 1 hr every 28 days
Measure Participants	32
Number (95% Confidence Interval) [percentage of participants]	9.3 23.8%

2. Secondary Outcome

Title	Best Overall PSA Response
Description	PSA response as stable disease or progressive disease, per Prostate-Specific Antigen Working Group criteria.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

Patients that received greater than one cycle of therapy and met criteria for stable or progressive disease according to Prostate-Specific Antigen Working Group criteria.

Arm/Group Title	Thalidomide and Doxil
Arm/Group Description	Thalidomide: 100 mg PO q day and escalation will occur bt 50 mg every 4 weeks to a maximum of 200mg Doxil: On day 1 of each cycle 40 mg/m2 IV over 1 hr every 28 days
Measure Participants	32
Stable disease	48.8
Progressive Disesase	43.7

3. Secondary Outcome

Title	Overall Survival
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Thalidomide and Doxil
Arm/Group Description	Thalidomide: 100 mg PO q day and escalation will occur bt 50 mg every 4 weeks to a maximum of 200mg Doxil: On day 1 of each cycle 40 mg/m2 IV over 1 hr every 28 days
Measure Participants	39
Median (95% Confidence Interval) [months]	12

4. Secondary Outcome

Title	Time to Progression
Description	Time from start of treatment until the disease progression per RECIST criteria.
Time Frame	Up to 18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Thalidomide and Doxil
Arm/Group Description	Thalidomide: 100 mg PO q day and escalation will occur bt 50 mg every 4 weeks to a maximum of 200mg Doxil: On day 1 of each cycle 40 mg/m2 IV over 1 hr every 28 days
Measure Participants	39
Median (95% Confidence Interval) [months]	3.7

Adverse Events

Arm/Group Title	Thalidomide and Doxil
Arm/Group Description	Combination of Thalidomide and Doxil Thalidomide: 100 mg PO q day and escalation will occur bt 50 mg every 4 weeks to a maximum of 200mg Doxil: On day 1 of each cycle 40 mg/m2 IV over 1 hr every 28 days
All Cause Mortality
	Thalidomide and Doxil
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Thalidomide and Doxil
	Affected / at Risk (%)	# Events
Total	9/39 (23.1%)
Gastrointestinal disorders
Pain, Intestine	1/39 (2.6%)
Pain, Pelvis	1/39 (2.6%)
General disorders
Edema: limb	1/39 (2.6%)
Pain - Other	1/39 (2.6%)
Investigations
INR (International Normalized Ratio of prothrombin time)	1/39 (2.6%)
Metabolism and nutrition disorders
Dehydration	1/39 (2.6%)
Musculoskeletal and connective tissue disorders
Arthritis (non-septic)	1/39 (2.6%)
Pain, Bone	1/39 (2.6%)
Respiratory, thoracic and mediastinal disorders
Atelectasis	1/39 (2.6%)
Dyspnea (shortness of breath)	2/39 (5.1%)
Other (Not Including Serious) Adverse Events
	Thalidomide and Doxil
	Affected / at Risk (%)	# Events
Total	39/39 (100%)
Blood and lymphatic system disorders
Blood/Bone Marrow - Other	5/39 (12.8%)
Hemoglobin	18/39 (46.2%)
Hemorrhage/Bleeding - Other	1/39 (2.6%)
Lymphatics - Other	3/39 (7.7%)
Cardiac disorders
Cardiac Arrhythmia - Other	1/39 (2.6%)
Palpitations	1/39 (2.6%)
Supraventricular and nodal arrhythmia, Sinus bradycardia	1/39 (2.6%)
Supraventricular and nodal arrhythmia, Supraventricular tachycardia	1/39 (2.6%)
Ear and labyrinth disorders
Auditory/Ear - Other	1/39 (2.6%)
Eye disorders
Ocular/Visual - Other	2/39 (5.1%)
Vision-blurred vision	1/39 (2.6%)
Watery eye (epiphora, tearing)	1/39 (2.6%)
Gastrointestinal disorders
Constipation	21/39 (53.8%)
Diarrhea	1/39 (2.6%)
Dry mouth/salivary gland (xerostomia)	3/39 (7.7%)
Dysphagia (difficulty swallowing)	2/39 (5.1%)
Gastrointestinal - Other	2/39 (5.1%)
Mucositis/stomatitis (clinical exam), Oral cavity	5/39 (12.8%)
Mucositis/stomatitis (functional/symptomatic), Oral cavity	1/39 (2.6%)
Nausea	10/39 (25.6%)
Taste alteration (dysgeusia)	5/39 (12.8%)
Vomiting	4/39 (10.3%)
Pain, Abdomen NOS	2/39 (5.1%)
Pain, Oral cavity	1/39 (2.6%)
Pain, Pelvis	1/39 (2.6%)
General disorders
Constitutional Symptoms - Other	2/39 (5.1%)
Fatigue (asthenia, lethargy, malaise)	25/39 (64.1%)
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)	4/39 (10.3%)
Rigors/chills	2/39 (5.1%)
Edema: limb	13/39 (33.3%)
Pain - Other	4/39 (10.3%)
Pain, Face	2/39 (5.1%)
Edema, larynx	1/39 (2.6%)
Infections and infestations
Infection with Grade 3 or 4 neutrophils , Lung (pneumonia)	1/39 (2.6%)
Infection - Other	1/39 (2.6%)
Infection with normal ANC or Grade 1 or 2 neutrophils, Dental-tooth	1/39 (2.6%)
Infection with normal ANC or Grade 1 or 2 neutrophils, Lung (pneumonia)	2/39 (5.1%)
Infection with normal ANC or Grade 1 or 2 neutrophils, Oral cavity-gums (gingivitis)	1/39 (2.6%)
Infection with normal ANC or Grade 1 or 2 neutrophils, Sinus	3/39 (7.7%)
Infection with unknown ANC, Sinus	1/39 (2.6%)
Investigations
Leukocytes (total WBC)	10/39 (25.6%)
Lymphopenia	2/39 (5.1%)
Neutrophils/granulocytes (ANC/AGC)	7/39 (17.9%)
Platelets	2/39 (5.1%)
Weight gain	1/39 (2.6%)
Weight loss	5/39 (12.8%)
AST, SGOT(serum glutamic oxaloacetic transaminase)	2/39 (5.1%)
Alkaline phosphatase	2/39 (5.1%)
Metabolism and nutrition disorders
Anorexia	9/39 (23.1%)
Dehydration	1/39 (2.6%)
Albumin, serum-low (hypoalbuminemia)	2/39 (5.1%)
Calcium, serum-high (hypercalcemia)	1/39 (2.6%)
Calcium, serum-low (hypocalcemia)	3/39 (7.7%)
Potassium, serum-high (hyperkalemia)	1/39 (2.6%)
Sodium, serum-low (hyponatremia)	1/39 (2.6%)
Musculoskeletal and connective tissue disorders
Muscle weakness, generalized or specific area (not due to neuropathy), Extraocular	1/39 (2.6%)
Muscle weakness, generalized or specific area (not due to neuropathy), Extremity-lower	1/39 (2.6%)
Musculoskeletal/Soft Tissue - Other	1/39 (2.6%)
Pain, Back	6/39 (15.4%)
Pain, Bone	1/39 (2.6%)
Pain, Extremity-limb	3/39 (7.7%)
Pain, Joint	9/39 (23.1%)
Nervous system disorders
Dizziness	8/39 (20.5%)
Extrapyramidal/involuntary movement/restlessness	1/39 (2.6%)
Memory impairment	1/39 (2.6%)
Neurology - Other	5/39 (12.8%)
Neuropathy: motor	2/39 (5.1%)
Neuropathy: sensory	14/39 (35.9%)
Somnolence/depressed level of consciousness	2/39 (5.1%)
Tremor	4/39 (10.3%)
Pain, Head/headache	2/39 (5.1%)
Psychiatric disorders
Insomnia	1/39 (2.6%)
Mood alteration, Anxiety	1/39 (2.6%)
Mood alteration, Depression	3/39 (7.7%)
Renal and urinary disorders
Hemorrhage, GU, Urinary NOS	1/39 (2.6%)
Incontinence, urinary	2/39 (5.1%)
Renal failure	1/39 (2.6%)
Renal/Genitourinary - Other	4/39 (10.3%)
Urinary frequency/urgency	3/39 (7.7%)
Urinary retention (including neurogenic bladder)	1/39 (2.6%)
Urine color change	1/39 (2.6%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)	3/39 (7.7%)
Hemorrhage, pulmonary/upper respiratory, Nose	1/39 (2.6%)
Pain, Chest wall	1/39 (2.6%)
Pain, Throat/pharynx/larynx	2/39 (5.1%)
Atelectasis	1/39 (2.6%)
Cough	5/39 (12.8%)
Dyspnea (shortness of breath)	5/39 (12.8%)
Nasal cavity/paranasal sinus reactions	2/39 (5.1%)
Pleural effusion (non-malignant)	2/39 (5.1%)
Pulmonary/Upper Respiratory - Other	1/39 (2.6%)
Skin and subcutaneous tissue disorders
Sweating (diaphoresis)	2/39 (5.1%)
Dermatology/Skin - Other	3/39 (7.7%)
Dry skin	5/39 (12.8%)
Hair loss/alopecia (scalp or body)	1/39 (2.6%)
Hyperpigmentation	1/39 (2.6%)
Pruritus/itching	3/39 (7.7%)
Rash/desquamation	13/39 (33.3%)
Rash: hand-foot skin reaction	2/39 (5.1%)
Urticaria (hives, welts, wheals)	1/39 (2.6%)
Vascular disorders
Hypotension	3/39 (7.7%)
Hot flashes/flushes	1/39 (2.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.