RAD001 and Bicalutamide for Androgen Independent Prostate Cancer

• Sponsor: Dana-Farber Cancer Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT00630344
• Collaborator: Beth Israel Deaconess Medical Center (Other), Novartis Pharmaceuticals (Industry)
• Enrollment: 36
• Locations: 2
• Arm: 1
• Duration (Months): 51
• Patients Per Site: 18
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

In the treatment of castration-resistant prostate cancer (CRPC), therapies will long response durations remain elusive as a result of the inherent ability of prostate cancer cells to develop iterative resistance. The goal of this study is to learn if the study drug RAD001 together with Bicalutamide can slow the growth of prostate cancer. The safety of the combination will also be studied.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: RAD001; Drug: Bicalutamide	Phase 2

Detailed Description

Bicalutamide, an androgen receptor (AR) antagonist, is frequently used as the first 'secondary hormonal therapy' in combination with another established agent (LHRH: luteinizing hormone-releasing hormone agonist/antagonist) to treat CRPC. A series of studies have shown that RAD001 through inhibition of mammalian target of rapamycin (mTOR) pathway has antitumor and anti-angiogenic activities. The hypothesis is that the combination of an antiandrogen and mTOR inhibitor would have additive and clinically significant effects in CRPC.

STATISTICAL CONSIDERATIONS:

The regimen will be considered promising if the rate of response/favorable outcome is 40% or greater. A rate of 20% (similar to that observed for bicalutamide alone) will not be considered worthy of further study. 38 patients (of whom 36 are assumed to be eligible) will be accrued to the study. If 11 or more patients have a favorable outcome (stable disease > 6 months or response), the combination will be considered worthy of further study. Given this design, there is a 9% probability of declaring the combination effective if the true favorable outcome rate is 20% and a 91% probability of declaring the combination effective if the true favorable outcome rate is 40%.

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of RAD001 and Bicalutamide for Androgen Independent Prostate Cancer
• Study Start Date: Feb 1, 2008
• Actual Primary Completion Date: May 1, 2012
• Actual Study Completion Date: May 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: RAD001 + Bicalutamide RAD001: once daily dose of 10 mg (5 mg tablets) Bicalutamide: once daily dose of 50 mg (50 mg tablets) 1 cycle=28 days Both agents are administered continuously until progression of disease or unacceptable toxicity.	Drug: RAD001; Other Names: everolimus ; Drug: Bicalutamide; Other Names: Casodex

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate [PSA was measured monthly and measurable disease on imaging assessed every 2 cycles in first 8 weeks and every 3 cycles thereafter. In this study cohort, patients were followed on treatment up to approximately 1 year.]

   Overall response rate is the percentage of patients achieving response taking into consideration measurable disease, bone metastases, and PSA. PSA declines in the absence of both measurable disease and the appearance of new bone lesions or a response in measurable disease without an increase in PSA or the appearance of new bone lesions. Patients with stable disease (SD) lasting at least 6 months will also be considered responders. Per RECIST guidelines, for target lesions, complete response (CR) is complete disappearance of all target lesions and partial response (PR) is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. CR or PR confirmation is required within 4 weeks. Per modified PSAWG2 criteria (Scher H, Halabi S, Tannock I et al. JCO 2008) PSA response is defined as PSA decline ≥ 50% from baseline confirmed by a second measurement at least 4 weeks later.

Secondary Outcome Measures

1. Incidence of Grade 4 Treatment-Related Toxicity [Assessed each cycle during therapy and up to 30 days post-therapy completion which is approximately 1 year for patients in this study cohort.]

   All grade 4 adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv3 as reported on case report forms were counted. Incidence is the number of patients experiencing at least one treatment-related grade 4 AE of any type during the time of observation.

2. Incidence of Grade 1-3 Treatment-Related Mucositis Toxicity [Assessed each cycle during therapy and up to 30 days post-therapy completion which is approximately 1 year for patients in this study cohort.]

   All grade 1-3 mucositis adverse events (AE) with treatment attribution of possible, probable or definite based on CTCAEv3 as reported on case report forms were counted. Incidence is the number of patients experiencing at least one treatment-related grade 1-3 mucositis AE during the time of observation.

3. Incidence of Grade 1-3 Treatment-Related Rash Toxicity [Assessed each cycle during therapy and up to 30 days post-therapy completion which is approximately 1 year for patients in this study cohort.]

   All grade 1-3 rash adverse events (AE) with treatment attribution of possible, probable or definite based on CTCAEv3 as reported on case report forms were counted. Incidence is the number of patients experiencing at least one treatment-related grade 1-3 rash AE during the time of observation.

4. Incidence of Grade 1-3 Treatment-Related Fatigue Toxicity [Assessed each cycle during therapy and up to 30 days post-therapy completion which is approximately 1 year for patients in this study cohort.]

   All grade 1-3 fatigue adverse events (AE) with treatment attribution of possible, probable or definite based on CTCAEv3 as reported on case report forms were counted. Incidence is the number of patients experiencing at least one treatment-related grade 1-3 fatigue AE during the time of observation.

5. Time to Progression (TTP) [PSA was measured monthly and measurable disease on imaging assessed every 2 cycles in first 8 weeks and every 3 cycles thereafter. In this study cohort, patients were followed on treatment up to approximately 1 year.]

   TTP estimated with Kaplan-Meier methods is defined as the time from treatment start to when PSA progression criteria is first met, or the date of measurable or non-measurable disease progression (PD). Absent progression, patients are censored at the date of the last PSA measurement. PSA progression is a ≥25% increase over baseline or nadir PSA, whichever is lowest with a minimum increase of 5 ng/mL. If PSA declines ≥50%, PSA progression is a ≥50% PSA increase above nadir with a minimum increase of 5 ng/mL or back to pretreatment baseline, whichever is lowest. PSA progression requires 2 week confirmation. Per RECIST, PD is at least a 20% increase in sum LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or appearance of new lesions. Non-measurable PD is defined as a worsening bone scan, as indicated by the appearance of two or more new lesions, the appearance of new non-bony metastases or a requirement for radiation therapy.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• 18 years of age or older

• Histologically documented prostate cancer

• Castration resistant prostate cancer defined as two rising PSAs on castration therapy

• Baseline PSA of 2ns/mL or greater

• Testosterone of 50ng/mL or less

• Patients on LHRH agonist/antagonist must continue therapy at the recommended dosing intervals

• Prior bicalutamide is allowed as long as treatment was for 6 months or longer

• Metastatic disease is not required

• Minimum of four weeks since any major surgery, completion of radiation, or completion of all prior systemic anticancer therapy

• ECOG Performance Status equal to or less than 2

• Adequate bone marrow and liver function as outlined by parameters in the protocol

Exclusion Criteria:

• Prior treatment with any investigational drug within the preceding 4 weeks

• Prior treatment with an mTOR inhibitor

• Fasting lipids over the parameters outlined in the protocol

• Chronic treatment with systemic steroids or another immunosuppressive agent

• Patients should not receive immunization with attenuated live vaccines during study period or within one week of study entry

• Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases

• Other malignancies within the past 3 years except for adequately treated or basal squamous cell carcinomas of the skin

• Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study

• Known history of HIV seropositivity

• Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001

• Patients with an active, bleeding diathesis or on oral anti-vitamin K medication (except low dose coumarin)

• Men able to conceive and unwilling to practice an effective method of birth control

• Known hypersensitivity to RAD001 or other rapamycins or to its excipients

• History of noncompliance to medical regimens

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02115
2	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115

Sponsors and Collaborators

• Dana-Farber Cancer Institute
• Beth Israel Deaconess Medical Center
• Novartis Pharmaceuticals

Investigators

• Study Chair: Mary-Ellen Taplin, MD, Dana-Farber Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Mary-Ellen Taplin, MD, Principal Investigator, Dana-Farber Cancer Institute
• ClinicalTrials.gov Identifier: NCT00630344
• Other Study ID Numbers: 07-316
• First Posted: Mar 7, 2008
• Last Update Posted: Dec 8, 2017
• Last Verified: Nov 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Mary-Ellen Taplin, MD, Principal Investigator, Dana-Farber Cancer Institute: RAD001; bicalutamide; androgen independent prostate cancer
• Additional relevant MeSH terms: Prostatic Neoplasms; Everolimus; Bicalutamide

Study Results

Participant Flow

Arm/Group Title	RAD001 + Bicalutamide
Arm/Group Description	RAD001: once daily dose of 10 mg (5 mg tablets) Bicalutamide: once daily dose of 50 mg (50 mg tablets) 1 cycle=28 days Both agents are administered continuously until progression of disease or unacceptable toxicity.
Period Title: Overall Study
STARTED	36
COMPLETED	0
NOT COMPLETED	36

Baseline Characteristics

Arm/Group Title	RAD-001 in Combination With Bicalutamide
Arm/Group Description	RAD001: once daily dose of 10 mg (5 mg tablets) Bicalutamide: once daily dose of 50 mg (50 mg tablets) 1 cycle=28 days Both agents are administered continuously until progression of disease or unacceptable toxicity.
Overall Participants	36
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	13 36.1%
>=65 years	23 63.9%
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	68
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	36 100%
Region of Enrollment (Count of Participants)
United States	36 100%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate
Description	Overall response rate is the percentage of patients achieving response taking into consideration measurable disease, bone metastases, and PSA. PSA declines in the absence of both measurable disease and the appearance of new bone lesions or a response in measurable disease without an increase in PSA or the appearance of new bone lesions. Patients with stable disease (SD) lasting at least 6 months will also be considered responders. Per RECIST guidelines, for target lesions, complete response (CR) is complete disappearance of all target lesions and partial response (PR) is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. CR or PR confirmation is required within 4 weeks. Per modified PSAWG2 criteria (Scher H, Halabi S, Tannock I et al. JCO 2008) PSA response is defined as PSA decline ≥ 50% from baseline confirmed by a second measurement at least 4 weeks later.
Time Frame	PSA was measured monthly and measurable disease on imaging assessed every 2 cycles in first 8 weeks and every 3 cycles thereafter. In this study cohort, patients were followed on treatment up to approximately 1 year.

Outcome Measure Data

Analysis Population Description

The analysis dataset is comprised of all treated patients.

Arm/Group Title	RAD-001 + Bicalutamide
Arm/Group Description	RAD001: once daily dose of 10 mg (5 mg tablets) Bicalutamide: once daily dose of 50 mg (50 mg tablets) 1 cycle=28 days Both agents are administered continuously until progression of disease or unacceptable toxicity.
Measure Participants	36
Number (90% Confidence Interval) [percentage of patients]	6

2. Secondary Outcome

Title	Incidence of Grade 4 Treatment-Related Toxicity
Description	All grade 4 adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv3 as reported on case report forms were counted. Incidence is the number of patients experiencing at least one treatment-related grade 4 AE of any type during the time of observation.
Time Frame	Assessed each cycle during therapy and up to 30 days post-therapy completion which is approximately 1 year for patients in this study cohort.

Outcome Measure Data

Analysis Population Description

The analysis dataset is comprised of all treated patients.

Arm/Group Title	RAD001 + Bicalutamide
Arm/Group Description	RAD001: once daily dose of 10 mg (5 mg tablets) Bicalutamide: once daily dose of 50 mg (50 mg tablets) 1 cycle=28 days Both agents are administered continuously until progression of disease or unacceptable toxicity.
Measure Participants	36
Count of Participants [Participants]	0 0%

3. Secondary Outcome

Title	Incidence of Grade 1-3 Treatment-Related Mucositis Toxicity
Description	All grade 1-3 mucositis adverse events (AE) with treatment attribution of possible, probable or definite based on CTCAEv3 as reported on case report forms were counted. Incidence is the number of patients experiencing at least one treatment-related grade 1-3 mucositis AE during the time of observation.
Time Frame	Assessed each cycle during therapy and up to 30 days post-therapy completion which is approximately 1 year for patients in this study cohort.

Outcome Measure Data

Analysis Population Description

The analysis dataset is comprised of all treated patients.

Arm/Group Title	RAD001 + Bicalutamide
Arm/Group Description	RAD001: once daily dose of 10 mg (5 mg tablets) Bicalutamide: once daily dose of 50 mg (50 mg tablets) 1 cycle=28 days Both agents are administered continuously until progression of disease or unacceptable toxicity.
Measure Participants	36
Count of Participants [Participants]	20 55.6%

4. Secondary Outcome

Title	Incidence of Grade 1-3 Treatment-Related Rash Toxicity
Description	All grade 1-3 rash adverse events (AE) with treatment attribution of possible, probable or definite based on CTCAEv3 as reported on case report forms were counted. Incidence is the number of patients experiencing at least one treatment-related grade 1-3 rash AE during the time of observation.
Time Frame	Assessed each cycle during therapy and up to 30 days post-therapy completion which is approximately 1 year for patients in this study cohort.

Outcome Measure Data

Analysis Population Description

The analysis dataset is comprised of all treated patients.

Arm/Group Title	RAD001 + Bicalutamide
Arm/Group Description	RAD001: once daily dose of 10 mg (5 mg tablets) Bicalutamide: once daily dose of 50 mg (50 mg tablets) 1 cycle=28 days Both agents are administered continuously until progression of disease or unacceptable toxicity.
Measure Participants	36
Count of Participants [Participants]	17 47.2%

5. Secondary Outcome

Title	Incidence of Grade 1-3 Treatment-Related Fatigue Toxicity
Description	All grade 1-3 fatigue adverse events (AE) with treatment attribution of possible, probable or definite based on CTCAEv3 as reported on case report forms were counted. Incidence is the number of patients experiencing at least one treatment-related grade 1-3 fatigue AE during the time of observation.
Time Frame	Assessed each cycle during therapy and up to 30 days post-therapy completion which is approximately 1 year for patients in this study cohort.

Outcome Measure Data

Analysis Population Description

The analysis dataset is comprised of all treated patients.

Arm/Group Title	RAD001 + Bicalutamide
Arm/Group Description	RAD001: once daily dose of 10 mg (5 mg tablets) Bicalutamide: once daily dose of 50 mg (50 mg tablets) 1 cycle=28 days Both agents are administered continuously until progression of disease or unacceptable toxicity.
Measure Participants	36
Count of Participants [Participants]	16 44.4%

6. Secondary Outcome

Title	Time to Progression (TTP)
Description	TTP estimated with Kaplan-Meier methods is defined as the time from treatment start to when PSA progression criteria is first met, or the date of measurable or non-measurable disease progression (PD). Absent progression, patients are censored at the date of the last PSA measurement. PSA progression is a ≥25% increase over baseline or nadir PSA, whichever is lowest with a minimum increase of 5 ng/mL. If PSA declines ≥50%, PSA progression is a ≥50% PSA increase above nadir with a minimum increase of 5 ng/mL or back to pretreatment baseline, whichever is lowest. PSA progression requires 2 week confirmation. Per RECIST, PD is at least a 20% increase in sum LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or appearance of new lesions. Non-measurable PD is defined as a worsening bone scan, as indicated by the appearance of two or more new lesions, the appearance of new non-bony metastases or a requirement for radiation therapy.
Time Frame	PSA was measured monthly and measurable disease on imaging assessed every 2 cycles in first 8 weeks and every 3 cycles thereafter. In this study cohort, patients were followed on treatment up to approximately 1 year.

Outcome Measure Data

Analysis Population Description

The analysis dataset is comprised of all treated patients.

Arm/Group Title	RAD001 + Bicalutamide
Arm/Group Description	RAD001: once daily dose of 10 mg (5 mg tablets) Bicalutamide: once daily dose of 50 mg (50 mg tablets) 1 cycle=28 days Both agents are administered continuously until progression of disease or unacceptable toxicity.
Measure Participants	36
Median (Full Range) [weeks]	8.7

Adverse Events

Time Frame	Assessed each cycle during therapy and up to 30 days post-therapy completion which is approximately 1 year for patients in this study cohort.
Arm/Group Title	RAD-001+ Bicalutamide
Arm/Group Description	RAD001: once daily dose of 10 mg (5 mg tablets) Bicalutamide: once daily dose of 50 mg (50 mg tablets) 1 cycle=28 days Both agents are administered continuously until progression of disease or unacceptable toxicity.
All Cause Mortality
	RAD-001+ Bicalutamide
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	RAD-001+ Bicalutamide
	Affected / at Risk (%)	# Events
Total	19/36 (52.8%)
Blood and lymphatic system disorders
Hemoglobin	2/36 (5.6%)
Eye disorders
Double vision	1/36 (2.8%)
Gastrointestinal disorders
Muco/stomatitis by exam- oral cavity	1/36 (2.8%)
General disorders
Fatigue	2/36 (5.6%)
Pain-other	1/36 (2.8%)
Infections and infestations
Infection neut-anal/perianl	1/36 (2.8%)
Investigations
Leukocytes	1/36 (2.8%)
Alkaline phosphatase	1/36 (2.8%)
CPK	1/36 (2.8%)
Creatinine	1/36 (2.8%)
Metabolism and nutrition disorders
Dehydration	1/36 (2.8%)
Hyperglycemia	3/36 (8.3%)
Hypophosphatemia	1/36 (2.8%)
Hyperkalemia	1/36 (2.8%)
Hyponatremia	2/36 (5.6%)
Musculoskeletal and connective tissue disorders
Bone-pain	1/36 (2.8%)
Nervous system disorders
Neuropathy CN XII tongue	1/36 (2.8%)
Speech impairment	1/36 (2.8%)
Syncope	1/36 (2.8%)
Renal and urinary disorders
Glomerular filtration rate	1/36 (2.8%)
Renal Failure	1/36 (2.8%)
Respiratory, thoracic and mediastinal disorders
Cough	1/36 (2.8%)
Skin and subcutaneous tissue disorders
Rash/desquamation	1/36 (2.8%)
Other (Not Including Serious) Adverse Events
	RAD-001+ Bicalutamide
	Affected / at Risk (%)	# Events
Total	35/36 (97.2%)
Blood and lymphatic system disorders
Hemoglobin	2/36 (5.6%)
Hematologic-other	1/36 (2.8%)
Lymphatics-other	1/36 (2.8%)
Cardiac disorders
Cardiac-other	1/36 (2.8%)
Eye disorders
Dry eye syndrome	1/36 (2.8%)
Double vision	1/36 (2.8%)
Vision-blurred	2/36 (5.6%)
Gastrointestinal disorders
Chelitis	1/36 (2.8%)
Constipation	5/36 (13.9%)
Diarrhea w/o prior colostomy	9/36 (25%)
Dry mouth	2/36 (5.6%)
Dysphagia	1/36 (2.8%)
Dyspepsia	2/36 (5.6%)
Muco/stomatitis by exam- oral cavity	10/36 (27.8%)
Muco/stomatitis (symptom) oral cavity	9/36 (25%)
Nausea	7/36 (19.4%)
Vomiting	3/36 (8.3%)
GI-other	2/36 (5.6%)
Abdomen- pain	1/36 (2.8%)
Dental/teeth/peridontal- pain	1/36 (2.8%)
Oral cavity- pain	2/36 (5.6%)
General disorders
Fatigue	14/36 (38.9%)
Fever w/o neutropenia	3/36 (8.3%)
Rigors/chills	1/36 (2.8%)
Constitutional- other	3/36 (8.3%)
Edema limb	3/36 (8.3%)
Chest/thoracic pain NOS	1/36 (2.8%)
Pain NOS	2/36 (5.6%)
Pain-other	5/36 (13.9%)
Infections and infestations
Infection Gr0-2 neut- anal/perianl	1/36 (2.8%)
Infection Gr0-2 neut- lung	1/36 (2.8%)
Injury, poisoning and procedural complications
Bruising	1/36 (2.8%)
Burn	1/36 (2.8%)
Investigations
Neutrophils	1/36 (2.8%)
Weight loss	4/36 (11.1%)
ALT- SGPT	3/36 (8.3%)
AST- SGOT	3/36 (8.3%)
Hypercholesterolemia	3/36 (8.3%)
CPK	6/36 (16.7%)
Creatinine	1/36 (2.8%)
Metabolism and nutrition disorders
Anorexia	7/36 (19.4%)
Hyperglycemia	1/36 (2.8%)
Hyperkalemia	2/36 (5.6%)
Hypokalemia	1/36 (2.8%)
Hyponatremia	1/36 (2.8%)
Hypertriglyceridemia	1/36 (2.8%)
Musculoskeletal and connective tissue disorders
Extremity upper (function)	1/36 (2.8%)
Nonneuropathic lower extr muscle weak	3/36 (8.3%)
Nonneuropathic generalized weakness	2/36 (5.6%)
Back- pain	7/36 (19.4%)
Bone- pain	2/36 (5.6%)
Buttock- pain	1/36 (2.8%)
Extremity-limb- pain	2/36 (5.6%)
Joint- pain	4/36 (11.1%)
Muscle- pain	1/36 (2.8%)
Neck- pain	2/36 (5.6%)
Nervous system disorders
Taste disturbance	6/36 (16.7%)
Nonneuropathic facial muscle weak	1/36 (2.8%)
Dizziness	2/36 (5.6%)
Extrapyramidal movement	1/36 (2.8%)
Memory impairment	1/36 (2.8%)
Neuropathy CN VI lateral deviation eye	1/36 (2.8%)
Neuropathy-sensory	1/36 (2.8%)
Tremor	1/36 (2.8%)
Head/headache	4/36 (11.1%)
Psychiatric disorders
Insomnia	3/36 (8.3%)
Depression	2/36 (5.6%)
Psychosis	1/36 (2.8%)
Renal and urinary disorders
Bladder- hemorrhage	1/36 (2.8%)
Urinary hemorrhage NOS	2/36 (5.6%)
Cystitis	1/36 (2.8%)
Obstruction-bladder	1/36 (2.8%)
Urinary frequency/urgency	4/36 (11.1%)
Reproductive system and breast disorders
Pelvic- pain	1/36 (2.8%)
Penis- pain	1/36 (2.8%)
Gynecomastia	3/36 (8.3%)
Respiratory, thoracic and mediastinal disorders
Nose- hemorrhage	2/36 (5.6%)
Throat/pharynx/larynx- pain	3/36 (8.3%)
Cough	7/36 (19.4%)
Dyspnea	5/36 (13.9%)
Pneumonitis/pulmonary infiltrates	3/36 (8.3%)
Pulmonary/Upper Respiratory-other	2/36 (5.6%)
Skin and subcutaneous tissue disorders
Dry skin	4/36 (11.1%)
Pruritus/itching	3/36 (8.3%)
Rash/desquamation	10/36 (27.8%)
Rash: acne/acneiform	6/36 (16.7%)
Erythema multiforme	2/36 (5.6%)
Skin-other	1/36 (2.8%)
Vascular disorders
Hypotension	1/36 (2.8%)
Hot flashes	2/36 (5.6%)
Hemorrhage-other	1/36 (2.8%)

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.