Study of 2 Different Doses of Revlimid in Biochemically Relapse Prostate Cancer

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)
• Overall Status: Completed
• CT.gov ID: NCT00348595
• Collaborator: Celgene Corporation (Industry)
• Enrollment: 77
• Location: 1
• Arms: 2
• Actual Duration (Months): 119.3
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

The primary objectives of the study are:

• To evaluate feasibility, safety and tolerance of 6 months administration of Revlimid at 5mg/day and 25mg/day, given orally in subjects with prostate cancer with evidence of biochemical relapse (M0) following local treatment (i.e., surgery or radiation).

• To assess the rate of PSA (prostatic specific antigen) progression at 6 months after treatment with 5mg/day and 25mg/day of Revlimid (CC-5013) in patients with evidence of biochemical relapse after local therapy.

The secondary objectives of the study are:

• To provide preliminary assessments on the effects of Revlimid (CC-5013) at 5mg/day and 25mg/day on various PSA constructs in the subject population (i.e., PSADT [Prostatic Specific Antigen Doubling Time] and PSA slope) by comparing pre and post treatment patterns in each arm.

• To evaluate preliminary pharmacodynamic correlations between serum revlimid concentrations and toxicity, PSA constructs and other evidence of disease progression.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: Revlimid	Phase 1/Phase 2

Detailed Description

Carcinoma of the prostate in the most commonly diagnosed malignancy among men in this country with approximately 232,090 new cases expected to be diagnosed in 2005. Unfortunately, despite local treatment, many men will demonstrate evidence of PSA recurrence. At the present time, there is no standard treatment fo these patients. The management of patients with PSA recurrence remains greatly controversial. Androgen deprivation is frequently employed in patients with evidence of rising PSA levels despite the fact that the effects on quantity and quality of life of androgen deprivation therapy at this stage, remains un-established. Toxicity of androgen deprivation therapy is a major factor to be considered in the decision process of employing the modality of treatment in patients with no symptoms associated with this disease. Because patients with biochemical relapse are mostly asymptomatic and typically have long survivals and disease free survivals, mush of the focus of new drug development has been with the use of non-cytotoxic compounds. This study is intended to provide preliminary evidence of a biological effect in a dose response manner assessing the effects of Revlimid (CC-5013) on PSA.

Study Design

• Study Type: Interventional
• Actual Enrollment: 77 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Phase I/II Double Blinded Randomized Study to Determine the Tolerability and Efficacy of 2 Different Doses of Revlimid (CC-5013, Lenalidomide) in Biochemically Relapsed Prostate Cancer Patients (M0) After Local Treatment
• Actual Study Start Date: Jul 20, 2006
• Actual Primary Completion Date: Jun 29, 2016
• Actual Study Completion Date: Jun 29, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1 5mg/day Arm: one 5 mg active Revlimid capsule and one 25 mg matched placebo capsules PO QAM (every morning) (at approximately the same time) days 1-21 days (28-day cycles).	Drug: Revlimid; one 5 mg/day capsule or one 25 mg/day capsule with matched placebo capsule day 1-21 (28 day cycle); Other Names: Lenalidomide
Active Comparator: 2 25 mg/day Arm: one 25 mg active Revlimid capsule and one 5 mg matched placebo capsule PO QAM (every morning) (at approximately the same time) days 1-21 (28 day cycles).	Drug: Revlimid; one 5 mg/day capsule or one 25 mg/day capsule with matched placebo capsule day 1-21 (28 day cycle); Other Names: Lenalidomide

Outcome Measures

Primary Outcome Measures

1. Safety, Feasibility and Tolerance of Revlimid as Assessed by Number of Participants Experiencing Grade 3 and 4 Adverse Events. [6 months post-intervention]

   Number of participants experiencing Grade 3 and 4 adverse events as defined by the National Cancer Institute Common Toxicity Criteria version 3.0

2. Number of Participants With Prostate-specific Antigen (PSA) Progression [6 months post-intervention]

   Number of participants with greater than or equal to 25% increase in PSA at 6 months

3. Change in of PSA Slope [Change from baseline to 6 months post-intervention]

   Mean change in PSA slope from baseline to 6 months. PSA slope was calculated using the regression of log PSA over 6 months in each patient. A negative mean change in PSA slope reflects a better outcome.

Secondary Outcome Measures

1. Plasma Concentration of Revilimid at Steady State [Day 21 of second treatment cycle]

   Mean plasma concentration (ng/mL) of Revilimid at steady state (Day 21 of second treatment cycle)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Histologically confirmed diagnosis of adenocarcinoma of the prostate (M0) with evidence of biochemical relapse after local therapy (i.e., surgery, radiation therapy, or both.) Baseline PSA must be greater or equal to 1 ng/ml.

• Confirmed rise in PSA shown by 2 PSA values at least 1 month apart, higher than a reference value noted within 6 months of study entry. Interim PSA values during the immediate pre-study six-month interval may demonstrate a "fluctuation" including a decline, however the study baseline PSA must have shown a rise within the pre-study 6-months period. Baseline PSA's must be determined within 4 weeks of study entry.

• All previous local modalities of treatment, including radiation and surgery, must have been discontinued at least 4 weeks prior to treatment in this study. May have received prior systemic chemotherapy, hormonal therapy, biologic or vaccine therapy. All treatment must have been discontinued for more than 6 months prior to study entry.

• Patients receiving intermittent hormonal therapy for their rising PSA state are considered eligible if testosterone level is above 150 ng/dl and treatment was discontinued greater than 6 months

• No clinical or radiological evidence of distant metastases (excluding prostascint scan).

• Serum testosterone > 150 ng/ml

• Disease free of prior malignancies for more than 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the breast.

• Able to take aspirin (ASA 81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use low molecular weight heparin). Lenalidomide increases the risk of thrombotic events in patients who are at high risk or with a history a thrombosis, in particular when combined with other drugs known to cause thrombosis.

Exclusion Criteria:

• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.

• Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.

• Known hypersensitivity to thalidomide.

• The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.

• Any prior use of Revlimid® (CC-5013).

• Concurrent use of other anti-cancer agents or treatments.

• Known brain metastases.

• Known positive for HIV or infectious hepatitis, type A, B or C.

• Any evidence of metastatic disease.

• Any increase in PSA while receiving neo-adjuvant or adjuvant therapy or intermittent hormonal therapy.

• More than one prior biologic or vaccine therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Harry and Jeanette Weinberg Building	Baltimore	Maryland	United States	21230

Sponsors and Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Celgene Corporation

Investigators

• Principal Investigator: Mario A Eisenberger, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• ClinicalTrials.gov Identifier: NCT00348595
• Other Study ID Numbers: J0798; RV-PCA-PI-069; NA_00013597; J0798
• First Posted: Jul 4, 2006
• Last Update Posted: Apr 12, 2019
• Last Verified: Apr 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: Prostate Cancer
• Additional relevant MeSH terms: Prostatic Neoplasms; Lenalidomide

Study Results

Participant Flow

Pre-assignment Detail	17 subjects were screen failures

Arm/Group Title	Revlimid 5mg/Day	Revlimid 25mg/Day
Arm/Group Description	One 5 mg active Revlimid capsule and one 25 mg matched placebo capsule given by mouth daily in the morning (at approximately the same time) on days 1-21 (28-day cycles).	One 25 mg active Revlimid capsule and one 5 mg matched placebo capsule given by mouth daily in the morning (at approximately the same time) on days 1-21 (28-day cycles).
Period Title: Overall Study
STARTED	26	34
COMPLETED	21	26
NOT COMPLETED	5	8

Baseline Characteristics

Arm/Group Title	Revlimid 5mg/Day	Revlimid 25mg/Day	Total
Arm/Group Description	One 5 mg active Revlimid capsule and one 25 mg matched placebo capsule given by mouth daily in the morning (at approximately the same time) on days 1-21 (28-day cycles), repeated monthly for 6 months or until dose-limiting toxicity or disease progression, as defined in the protocol.	One 25 mg active Revlimid capsule and one 5 mg matched placebo capsule given by mouth daily in the morning (at approximately the same time) on days 1-21 (28-day cycles), repeated monthly for 6 months or until dose-limiting toxicity or disease progression, as defined in the protocol.	Total of all reporting groups
Overall Participants	26	34	60
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.7 (7.1)	63.1 (7.2)	63.4 (7.1)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	26 100%	34 100%	60 100%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
United States	26 100%	34 100%	60 100%
Gleason score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	7.1 (1.0)	7.3 (1.1)	7.2 (1.05)
Local therapy (Count of Participants)
Radical prostatectomy	12 46.2%	12 35.3%	24 40%
Radiation therapy	4 15.4%	8 23.5%	12 20%
Surgery and Radiation therapy	10 38.5%	14 41.2%	24 40%
Prior androgen deprivation therapy	8 30.8%	11 32.4%	19 31.7%
Serum testosterone ((ng/dL)) [Mean (Full Range) ]
Mean (Full Range) [(ng/dL)]	374	342	358
Prostate Specific Antigen (PSA) (ng/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ng/mL]	11.9 (11.9)	12.4 (13.6)	12.2 (12.8)
PSA doubling time (PSADT) (Count of Participants)
< 3 months	6 23.1%	10 29.4%	16 26.7%
3-8.9 months	13 50%	16 47.1%	29 48.3%
≥ 9 months	7 26.9%	8 23.5%	15 25%
Pre-treatment PSA slopes (log PSA/month) [Mean (Full Range) ]
Mean (Full Range) [log PSA/month]	0.16	0.18	0.17

Outcome Measures

1. Primary Outcome

Title	Safety, Feasibility and Tolerance of Revlimid as Assessed by Number of Participants Experiencing Grade 3 and 4 Adverse Events.
Description	Number of participants experiencing Grade 3 and 4 adverse events as defined by the National Cancer Institute Common Toxicity Criteria version 3.0
Time Frame	6 months post-intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Revlimid 5mg/Day	Revlimid 25mg/Day
Arm/Group Description	One 5 mg active Revlimid capsule and one 25 mg matched placebo capsule given by mouth daily in the morning (at approximately the same time) on days 1-21 (28-day cycles).	One 25 mg active Revlimid capsule and one 5 mg matched placebo capsule given by mouth daily in the morning (at approximately the same time) on days 1-21 (28-day cycles).
Measure Participants	26	34
Count of Participants [Participants]	3 11.5%	10 29.4%

2. Primary Outcome

Title	Number of Participants With Prostate-specific Antigen (PSA) Progression
Description	Number of participants with greater than or equal to 25% increase in PSA at 6 months
Time Frame	6 months post-intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Revlimid 5mg/Day	Revlimid 25mg/Day
Arm/Group Description	One 5 mg active Revlimid capsule and one 25 mg matched placebo capsule given by mouth daily in the morning (at approximately the same time) on days 1-21 (28-day cycles).	One 25 mg active Revlimid capsule and one 5 mg matched placebo capsule given by mouth daily in the morning (at approximately the same time) on days 1-21 (28-day cycles).
Measure Participants	26	34
Count of Participants [Participants]	7 26.9%	5 14.7%

3. Primary Outcome

Title	Change in of PSA Slope
Description	Mean change in PSA slope from baseline to 6 months. PSA slope was calculated using the regression of log PSA over 6 months in each patient. A negative mean change in PSA slope reflects a better outcome.
Time Frame	Change from baseline to 6 months post-intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Revlimid 5mg/Day	Revlimid 25mg/Day
Arm/Group Description	One 5 mg active Revlimid capsule and one 25 mg matched placebo capsule given by mouth daily in the morning (at approximately the same time) on days 1-21 (28-day cycles).	One 25 mg active Revlimid capsule and one 5 mg matched placebo capsule given by mouth daily in the morning (at approximately the same time) on days 1-21 (28-day cycles).
Measure Participants	26	34
Mean (95% Confidence Interval) [log PSA]	-0.033	-0.172

4. Secondary Outcome

Title	Plasma Concentration of Revilimid at Steady State
Description	Mean plasma concentration (ng/mL) of Revilimid at steady state (Day 21 of second treatment cycle)
Time Frame	Day 21 of second treatment cycle

Outcome Measure Data

Analysis Population Description

Data was only evaluable in 20/26 and 27/34 participants from the 5mg and 25mg arms, respectively.

Arm/Group Title	Revlimid 5mg/Day	Revlimid 25mg/Day
Arm/Group Description	One 5 mg active Revlimid capsule and one 25 mg matched placebo capsule given by mouth daily in the morning (at approximately the same time) on days 1-21 (28-day cycles).	One 25 mg active Revlimid capsule and one 5 mg matched placebo capsule given by mouth daily in the morning (at approximately the same time) on days 1-21 (28-day cycles).
Measure Participants	20	27
Mean (95% Confidence Interval) [ng/mL]	12.67	65.14

Adverse Events

Time Frame	Collected monthly, up to 44 months
Arm/Group Title	Revlimid 5mg/Day		Revlimid 25mg/Day
Arm/Group Description	One 5 mg active Revlimid capsule and one 25 mg matched placebo capsule given by mouth daily in the morning (at approximately the same time) on days 1-21 (28-day cycles), repeated monthly for 6 months or until dose-limiting toxicity or disease progression, as defined in the protocol.		One 25 mg active Revlimid capsule and one 5 mg matched placebo capsule given by mouth daily in the morning (at approximately the same time) on days 1-21 (28-day cycles), repeated monthly for 6 months or until dose-limiting toxicity or disease progression, as defined in the protocol.
All Cause Mortality
	Revlimid 5mg/Day		Revlimid 25mg/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/26 (0%)		0/34 (0%)
Serious Adverse Events
	Revlimid 5mg/Day		Revlimid 25mg/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/26 (11.5%)		10/34 (29.4%)
Blood and lymphatic system disorders
Neutropenia	0/26 (0%)	0	5/34 (14.7%)	5
Nervous system disorders
Fatigue	1/26 (3.8%)	1	1/34 (2.9%)	1
Skin and subcutaneous tissue disorders
Severe Rash	0/26 (0%)	0	2/34 (5.9%)	2
Vascular disorders
venous thromboembolism	2/26 (7.7%)	2	2/34 (5.9%)	2
Other (Not Including Serious) Adverse Events
	Revlimid 5mg/Day		Revlimid 25mg/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/26 (100%)		34/34 (100%)
Blood and lymphatic system disorders
anemia	7/26 (26.9%)	7	10/34 (29.4%)	10
Lymphopenia	1/26 (3.8%)	1	8/34 (23.5%)	8
Neutropenia	5/26 (19.2%)	5	9/34 (26.5%)	9
Thrombocytopenia	4/4 (100%)	4	8/34 (23.5%)	8
Eye disorders
Blurred Vision	1/26 (3.8%)	1	2/34 (5.9%)	2
Dry Eye	2/26 (7.7%)	2	2/34 (5.9%)	2
Gastrointestinal disorders
Constipation	10/26 (38.5%)	10	15/34 (44.1%)	15
Dysphagia	0/26 (0%)	0	5/34 (14.7%)	5
Anal Pain	1/26 (3.8%)	1	0/34 (0%)	0
Abdominal Pain	3/26 (11.5%)	3	6/34 (17.6%)	6
Diarrhea	2/26 (7.7%)	2	5/34 (14.7%)	5
Dry Mouth	1/26 (3.8%)	1	5/34 (14.7%)	5
Investigations
Increased of SGOT	2/26 (7.7%)	2	8/34 (23.5%)	8
Metabolism and nutrition disorders
Hyperglycemia	11/26 (42.3%)	11	14/34 (41.2%)	14
Musculoskeletal and connective tissue disorders
Back Pain	4/26 (15.4%)	4	2/34 (5.9%)	2
Nervous system disorders
Fatigue	12/26 (46.2%)	12	29/34 (85.3%)	29
Muscular Cramping	5/26 (19.2%)	5	14/34 (41.2%)	14
Dizziness	4/26 (15.4%)	4	5/34 (14.7%)	5
Headache	4/26 (15.4%)	4	5/34 (14.7%)	5
Psychiatric disorders
Depression	0/26 (0%)	0	1/34 (2.9%)	1
Respiratory, thoracic and mediastinal disorders
Cough	2/26 (7.7%)	2	5/34 (14.7%)	5
Skin and subcutaneous tissue disorders
Pruritus	8/26 (30.8%)	8	15/34 (44.1%)	15
Rash	7/26 (26.9%)	7	15/34 (44.1%)	15
Alopecia	0/26 (0%)	0	5/34 (14.7%)	5
Dry Skin	4/26 (15.4%)	4	5/34 (14.7%)	5
Vascular disorders
Flushing	0/26 (0%)	0	4/34 (11.8%)	4

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.