GRAY-B: GEM STUDY: Radiation And Yervoy in Patients With Melanoma and Brain Metastases

• Sponsor: Grupo Español Multidisciplinar de Melanoma (Other)
• Overall Status: Completed
• CT.gov ID: NCT02115139
• Collaborator: Bristol-Myers Squibb (Industry)
• Enrollment: 58
• Locations: 12
• Arm: 1
• Actual Duration (Months): 51.9
• Patients Per Site: 4.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Ipilimumab adds a clinical benefit to radiation therapy in patients with melanoma metastatic to the brain.

Melanoma is the third most common cancer causing brain metastases, after cancers of the lung and breast, which appears to reflect the relative propensity of melanoma to metastasize to the central nervous system (CNS). Brain metastases are responsible for 20 to 54 percent of deaths in patients with melanoma, and among those with documented brain metastases, these lesions contribute to death in up to 95 percent of cases, with an estimated median overall survival ranging between 1.8 and 10.5 months, depending upon other prognostic factors.

Ipilimumab is an anti-Cytotoxic T-Lymphocyte Antigen 4 (anti-CTLA4) monoclonal antibody that has demonstrated a clinically relevant and statistically significant improvement in overall survival, either alone (second line) or in combination with dacarbazine (DTIC) in 1st line.

Ipilimumab has shown activity against brain metastases.

According to the European Medicines Agency (EMA) approved label for Yervoy®, the use of glucocorticoids at baseline (commonly prescribed when brain metastases are diagnosed) should be avoided before the administration of ipilimumab. Data show that the use of even high doses of glucocorticoids for the management of immune-related adverse events do not decrease the efficacy of Yervoy®. There is no documented experience on the efficacy of Yervoy® when given concomitantly with radiation therapy and glucocorticoids.

In experimental models, radiation therapy is synergistic to anti-Cytotoxic T-Lymphocyte Antigen 4 (anti-CTLA4) strategies (abscopal effect).

There are no published results from clinical trials on the interaction between radiation therapy and ipilimumab.

Condition or Disease	Intervention/Treatment	Phase
Melanoma; Brain Metastases	Drug: Ipilimumab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 58 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Single Arm, Phase 2 Clinical Study on the Combination of Radiation Therapy and Ipilimumab, for the Treatment of Patients With Melanoma and Brain Metastases
• Actual Study Start Date: Apr 4, 2014
• Actual Primary Completion Date: Dec 31, 2016
• Actual Study Completion Date: Jul 31, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ipilimumab Ipilimumab 3mg/Kg iv q 3 weeks for 4 cycles Whole-brain radiotherapy (WBRT) 30 Gy in 10 fractions (or radiobiological equivalent schedule, after Sponsor approval), starting between Cycle 1 Day 2 and Cycle 2 Day 1	Drug: Ipilimumab; Ipilimumab 3mg/Kg iv q 3 weeks for 4 cycles; Other Names: Experimental

Outcome Measures

Primary Outcome Measures

1. 1-year Survival Rate [Expected average of 3 weeks during for the first 6 months, then every 3 months.]

   During treatment period, there will be assessments every cycle. After end of treatment every 3 month.

Secondary Outcome Measures

1. Progression-Free Survival (PFS) [Within 4 weeks before start treatment, week 12, 17+/-1 and every 9 + / -1 weeks until progression up to 12 months after last patient treatment initiation.]

   Median time from treatment initiation to progression of disease

2. Intracranial PFS [Within 4 weeks before start treatment, week 12, 17+/-1 and every 9 + / -1 weeks until progression up to 12 months after last patient treatment initiation.]

   median, 6-month PFS rate

3. Extracranial PFS [Within 4 weeks before start treatment, week 12, 17+/-1 and every 9 + / -1 weeks until progression up to 12 months after last patient treatment initiation.]

   median, 6-month PFS rate

4. Overall Survival [Expected average of 3 weeks during for the first 6 months, then every 3 months.]

   median value for OS estimated by kaplan meier method

5. Response Rate [Within 4 weeks before start treatment, week 12, 17+/-1 and every 9 + / -1 weeks until progression up to 12 months after last patient treatment initiation.]

   Global and Immune-related response criteria

6. Adverse Event Rates [Expected average of 3 weeks during for the first 6 months, then every 3 months.]

   Number of patients with at least one treatment-related toxicity, classified by grade.

7. Rate of Dose Delays/Reductions and Treatment Exposure. [Expected average of 3 weeks during for the first 6 months, then every 3 months.]

   Treatment feasibility. Number of patients with treatment delays and reductions, categorized as function of the number of events (reductions/delays)

Other Outcome Measures

1. Correlation of Biomarker Expression and PFS. [Within 28 days before start treatment, just before the start treatment, then expected average of 3 weeks for the first 12 weeks]

   Translational study. PFS outcome reported by subgroups according to BRAF mutation status

2. Intrapatient Variation of Quantitative Apparent Diffusion Coefficients of Serial Diffusion-weighted Magnetic Resonance Imaging [Baseline and 4 weeks after WBRT]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Willing and able to give written informed consent.

2. Histologic diagnosis of melanoma.

3. First episode of radiological evidence of brain metastases

4. Be over the age of 18 years old

5. Radiation Therapy Oncology Group-recursive partitioning analysis (RTOG-RPA) class 2

6. Karnofsky performance status (PS) more than 70%

7. Barthel Index of Activities of Daily Living more than 10

8. Measurable disease (mWHO criteria).

9. Adequate organ function as determine by the following criteria:

• White blood count (WBC) more or equal to 2000/ microliter (uL)

• Absolute neutrophil count (ANC) more than 1.5 x 109/L.

• Platelet count more than 75 x 109/L.

• Hemoglobin more than 9 g/dL. If the patient received a red blood count (RBC) transfusion, the required value of hemoglobin should be met at least 1 week after the most recent transfusion.

• Serum creatinine less or equal to 2.0 x upper limit of normal (ULN).

• Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) less or equal to 2.5 x ULN for patients without liver metastasis, or less or equal to 5 times for liver metastases.

• Total bilirubin less or equal 2.0 x ULN, (except patients with Gilbert's Syndrome, who must have a total bilirubin less than 3.0 mg/dL)

1. Persons of reproductive potential must agree to use an adequate method of contraception throughout treatment and for at least 26 weeks after ipilimumab is stopped

Exclusion Criteria:

1. Patients with melanoma and brain metastases with any of the following disease-specific characteristics:

• Documented evidence of prior progression of melanoma to an ipilimumab-containing regimen (i.e. received at least 2 doses of ipilimumab for either advanced disease or in the adjuvant setting and the disease progressed/relapsed (according to mWHO criteria) within 24 weeks since the first dose of ipilimumab)

• Prior radiation therapy to the brain

• Other prior antineoplastic therapies for brain metastases.

• Patients with cerebral metastases as the only location of the disease, for which local therapy (neurosurgery, radiosurgery) could achieve a disease-free status

• Patients with a rapid clinical deterioration, or with risk of herniation, or who require unstable ascending dosing of supportive medication in the last week -including anti-convulsivants, steroids and analgesics-, or who require dexamethasone more than 16 mg/d (or other glucocorticoid at an equipotent dose), or with a high lactate dehydrogenase (LDH) more than 2 x ULN.

1. Any other malignancy form which the patient has been disease-free for less than 5 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix, or incidental prostate cancer.

2. Uncontrolled diabetes mellitus (HbA1c more than 9 %)

3. Autoimmune disease other than vitiligo or past thyroiditis under substitutive hormone therapy: Patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's Disease, are excluded from this study, as are patients with a history of symptomatic disease (eg, rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [eg, Wegener's Granulomatosis]); motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre Syndrome and Myasthenia Gravis).

4. Other chronic intestinal diseases associated with diarrhea.

5. Active infection or other serious illness or medical condition.

6. Known active or chronic infection with HIV, Hepatitis B, or Hepatitis C.

7. Concomitant therapy with any of the following: interleukin-2 (IL-2), interferon, or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigation therapies; or chronic use of systemic corticosteroids (used for the management of non-cancer related illnesses), either concomitantly or during the last 30 days prior to the beginning of the treatment.

8. Any experimental therapy administered in the past 30 days prior to the beginning of the treatment.

9. Any non-oncology vaccine therapy used for the prevention of infectious diseases (for up to 4 weeks prior to or after any dose of blinded study drug) (see definitions in protocol text)

10. Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (eg, infectious) illness.

11. Any other general, medical or psychological conditions which in the opinion of the investigator will make the administration of ipilimumab hazardous, or that would preclude appropriate informed consent or compliance with the protocol, or obscure the interpretation of eventual adverse events (AEs).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	ICO Badalona	Badalona		Spain
2	H. Clinic de Barcelona	Barcelona		Spain
3	Hospital Vall d'Hebron	Barcelona		Spain
4	H. Insular de Canarias	Las Palmas de Gran Canaria		Spain
5	H. U. Gregorio Marañón	Madrid		Spain
6	Hospital Universitario 12 de Octubre	Madrid		Spain
7	Clínica Universidad de Navarra	Pamplona		Spain
8	H. Clínico de Santiago	Santiago de Compostela		Spain
9	H.U. Virgen Macarena	Sevilla		Spain
10	H. Virgen de la Salud	Toledo		Spain
11	H. General de Valencia	Valencia		Spain
12	Instituto Valenciano de Oncología	Valencia		Spain

Sponsors and Collaborators

• Grupo Español Multidisciplinar de Melanoma
• Bristol-Myers Squibb

Investigators

• Study Chair: José A López-Martín, MD, Hospital Universitario 12 de Octubre - GEM

Study Documents (Full-Text)

• Study Protocol - Nov 28, 2013
• Statistical Analysis Plan - Nov 28, 2013

More Information

Publications

None provided.

• Responsible Party: Grupo Español Multidisciplinar de Melanoma
• ClinicalTrials.gov Identifier: NCT02115139
• Other Study ID Numbers: GEM 1202; 2013-001132-22
• First Posted: Apr 15, 2014
• Last Update Posted: Jul 1, 2021
• Last Verified: Jun 1, 2021

• Keywords provided by Grupo Español Multidisciplinar de Melanoma: melanoma; brain; metastases; Patients with melanoma and brain metastases
• Additional relevant MeSH terms: Melanoma; Neoplasm Metastasis; Neoplasms, Second Primary; Brain Neoplasms; Ipilimumab

Study Results

Participant Flow

Recruitment Details	58 patients were enrolled and fulfilled the inclusion criteria, analyzed for safety. During the trial 7 patients discontinued treatment before completion, so the total of patients for efficacy analysis was 51.

Arm/Group Title	Ipilimumab
Arm/Group Description	Ipilimumab 3mg/Kg iv q 3 weeks for 4 cycles Whole-brain radiotherapy (WBRT) 30 Gy in 10 fractions (or radiobiological equivalent schedule, after Sponsor approval), starting between Cycle 1 Day 2 and Cycle 2 Day 1 Ipilimumab: Ipilimumab 3mg/Kg iv q 3 weeks for 4 cycles
Period Title: Overall Study
STARTED	58
COMPLETED	51
NOT COMPLETED	7

Baseline Characteristics

Arm/Group Title	Ipilimumab
Arm/Group Description	Ipilimumab 3mg/Kg iv q 3 weeks for 4 cycles Whole-brain radiotherapy (WBRT) 30 Gy in 10 fractions (or radiobiological equivalent schedule, after Sponsor approval), starting between Cycle 1 Day 2 and Cycle 2 Day 1 Ipilimumab: Ipilimumab 3mg/Kg iv q 3 weeks for 4 cycles
Overall Participants	58
Age (Years) [Median (Full Range) ]
Median (Full Range) [Years]	66
Sex: Female, Male (Count of Participants)
Female	22 37.9%
Male	36 62.1%
Region of Enrollment (Count of Participants)
Spain	58 100%
Karnofsky performance status (KPS) (Count of Participants)
90-100	42 72.4%
70-80	15 25.9%
Not evaluable (NE)	1 1.7%
Barthel index (Count of Participants)
Lower than 15	2 3.4%
15-20	56 96.6%
BRAF mutational status (Count of Participants)
Mutated	20 34.5%
Native	30 51.7%
Not evaluated (NE)	8 13.8%
Number of previous treatment lines (Count of Participants)
No previous lines	29 50%
1 previous line	20 34.5%
2 or more previous lines	9 15.5%
Number of brain metastasis (Count of Participants)
Unic brain lesion	14 24.1%
Multiple brain lesions	43 74.1%
Not especified (NE)	1 1.7%
Corticoid use (Count of Participants)
Yes	25 43.1%
No	33 56.9%
Lactate dehydrogenase (LDH) blood levels (Count of Participants)
Yes	24 41.4%
No	34 58.6%
Yes	9 15.5%
No	49 84.5%

Outcome Measures

1. Primary Outcome

Title	1-year Survival Rate
Description	During treatment period, there will be assessments every cycle. After end of treatment every 3 month.
Time Frame	Expected average of 3 weeks during for the first 6 months, then every 3 months.

Outcome Measure Data

Analysis Population Description

Efficacy cohort, all patients that fulfill eligibility and completed the treatment with radiotherapy

Arm/Group Title	Ipilimumab
Arm/Group Description	Ipilimumab 3mg/Kg iv q 3 weeks for 4 cycles Whole-brain radiotherapy (WBRT) 30 Gy in 10 fractions (or radiobiological equivalent schedule, after Sponsor approval), starting between Cycle 1 Day 2 and Cycle 2 Day 1 Ipilimumab: Ipilimumab 3mg/Kg iv q 3 weeks for 4 cycles
Measure Participants	51
Number (95% Confidence Interval) [Percentage of patients alive at 1 year]	31.8

2. Secondary Outcome

Title	Progression-Free Survival (PFS)
Description	Median time from treatment initiation to progression of disease
Time Frame	Within 4 weeks before start treatment, week 12, 17+/-1 and every 9 + / -1 weeks until progression up to 12 months after last patient treatment initiation.

Outcome Measure Data

Analysis Population Description

Efficacy population (patients that fulfill eligibility and completed the treatment with radiotherapy)

Arm/Group Title	Ipilimumab
Arm/Group Description	Ipilimumab 3mg/Kg iv q 3 weeks for 4 cycles Whole-brain radiotherapy (WBRT) 30 Gy in 10 fractions (or radiobiological equivalent schedule, after Sponsor approval), starting between Cycle 1 Day 2 and Cycle 2 Day 1 Ipilimumab: Ipilimumab 3mg/Kg iv q 3 weeks for 4 cycles
Measure Participants	51
Median (95% Confidence Interval) [Months]	3.11

3. Secondary Outcome

Title	Intracranial PFS
Description	median, 6-month PFS rate
Time Frame	Within 4 weeks before start treatment, week 12, 17+/-1 and every 9 + / -1 weeks until progression up to 12 months after last patient treatment initiation.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Extracranial PFS
Description	median, 6-month PFS rate
Time Frame	Within 4 weeks before start treatment, week 12, 17+/-1 and every 9 + / -1 weeks until progression up to 12 months after last patient treatment initiation.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Overall Survival
Description	median value for OS estimated by kaplan meier method
Time Frame	Expected average of 3 weeks during for the first 6 months, then every 3 months.

Outcome Measure Data

Analysis Population Description

Efficacy population (patients that comply with eligibility and completed radiotherapy treatment)

Arm/Group Title	Ipilimumab
Arm/Group Description	Ipilimumab 3mg/Kg iv q 3 weeks for 4 cycles Whole-brain radiotherapy (WBRT) 30 Gy in 10 fractions (or radiobiological equivalent schedule, after Sponsor approval), starting between Cycle 1 Day 2 and Cycle 2 Day 1 Ipilimumab: Ipilimumab 3mg/Kg iv q 3 weeks for 4 cycles
Measure Participants	51
Median (95% Confidence Interval) [Months]	4.73

6. Secondary Outcome

Title	Response Rate
Description	Global and Immune-related response criteria
Time Frame	Within 4 weeks before start treatment, week 12, 17+/-1 and every 9 + / -1 weeks until progression up to 12 months after last patient treatment initiation.

Outcome Measure Data

Analysis Population Description

Efficacy population

Arm/Group Title	Ipilimumab
Arm/Group Description	Ipilimumab 3mg/Kg iv q 3 weeks for 4 cycles Whole-brain radiotherapy (WBRT) 30 Gy in 10 fractions (or radiobiological equivalent schedule, after Sponsor approval), starting between Cycle 1 Day 2 and Cycle 2 Day 1 Ipilimumab: Ipilimumab 3mg/Kg iv q 3 weeks for 4 cycles
Measure Participants	51
Complete Response (CR)	2 3.4%
Partial response (PR)	3 5.2%
Stable disease (SD)	12 20.7%
Progression disease (PD)	19 32.8%
Not evaluable (NE)	15 25.9%
Complete Response (CR)	2 3.4%
Partial response (PR)	3 5.2%
Stable disease (SD)	12 20.7%
Progression disease (PD)	17 29.3%
Not evaluable (NE)	17 29.3%

7. Secondary Outcome

Title	Adverse Event Rates
Description	Number of patients with at least one treatment-related toxicity, classified by grade.
Time Frame	Expected average of 3 weeks during for the first 6 months, then every 3 months.

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Ipilimumab
Arm/Group Description	Ipilimumab 3mg/Kg iv q 3 weeks for 4 cycles Whole-brain radiotherapy (WBRT) 30 Gy in 10 fractions (or radiobiological equivalent schedule, after Sponsor approval), starting between Cycle 1 Day 2 and Cycle 2 Day 1 Ipilimumab: Ipilimumab 3mg/Kg iv q 3 weeks for 4 cycles
Measure Participants	58
Yes	37 63.8%
No	21 36.2%
Yes	11 19%
No	47 81%

8. Secondary Outcome

Title	Rate of Dose Delays/Reductions and Treatment Exposure.
Description	Treatment feasibility. Number of patients with treatment delays and reductions, categorized as function of the number of events (reductions/delays)
Time Frame	Expected average of 3 weeks during for the first 6 months, then every 3 months.

Outcome Measure Data

Analysis Population Description

safety population

Arm/Group Title	Ipilimumab
Arm/Group Description	Ipilimumab 3mg/Kg iv q 3 weeks for 4 cycles Whole-brain radiotherapy (WBRT) 30 Gy in 10 fractions (or radiobiological equivalent schedule, after Sponsor approval), starting between Cycle 1 Day 2 and Cycle 2 Day 1 Ipilimumab: Ipilimumab 3mg/Kg iv q 3 weeks for 4 cycles
Measure Participants	58
None	43 74.1%
1 event	12 20.7%
2 events	2 3.4%
3 events	1 1.7%
4 events	0 0%
None	50 86.2%
1 event	5 8.6%
2 events	1 1.7%
3 events	1 1.7%
4 events	1 1.7%

9. Other Pre-specified Outcome

Title	Correlation of Biomarker Expression and PFS.
Description	Translational study. PFS outcome reported by subgroups according to BRAF mutation status
Time Frame	Within 28 days before start treatment, just before the start treatment, then expected average of 3 weeks for the first 12 weeks

Outcome Measure Data

Analysis Population Description

efficacy population

Arm/Group Title	Ipilimumab
Arm/Group Description	Ipilimumab 3mg/Kg iv q 3 weeks for 4 cycles Whole-brain radiotherapy (WBRT) 30 Gy in 10 fractions (or radiobiological equivalent schedule, after Sponsor approval), starting between Cycle 1 Day 2 and Cycle 2 Day 1 Ipilimumab: Ipilimumab 3mg/Kg iv q 3 weeks for 4 cycles
Measure Participants	51
Progression disease	5 8.6%
No progression	12 20.7%
Not applicable	34 58.6%
Progression disease	7 12.1%
No progression	19 32.8%
Not applicable	25 43.1%

10. Other Pre-specified Outcome

Title	Intrapatient Variation of Quantitative Apparent Diffusion Coefficients of Serial Diffusion-weighted Magnetic Resonance Imaging
Time Frame	Baseline and 4 weeks after WBRT

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Throughout the study period, from inclusion to 30 days after treatment has ended. Approximately 1 year
Arm/Group Title	Ipilimumab
Arm/Group Description	Ipilimumab 3mg/Kg iv q 3 weeks for 4 cycles Whole-brain radiotherapy (WBRT) 30 Gy in 10 fractions (or radiobiological equivalent schedule, after Sponsor approval), starting between Cycle 1 Day 2 and Cycle 2 Day 1 Ipilimumab: Ipilimumab 3mg/Kg iv q 3 weeks for 4 cycles
All Cause Mortality
	Ipilimumab
	Affected / at Risk (%)	# Events
Total	40/58 (69%)
Serious Adverse Events
	Ipilimumab
	Affected / at Risk (%)	# Events
Total	33/58 (56.9%)
Blood and lymphatic system disorders
Anemia	1/58 (1.7%)
Eye disorders
Hemianopsia	1/58 (1.7%)
Gastrointestinal disorders
Diarrhoea	6/58 (10.3%)
Gastric Hemorrage	1/58 (1.7%)
Vomiting	2/58 (3.4%)
Duodenal perforation	1/58 (1.7%)
General disorders
Fever	2/58 (3.4%)
Malaise	4/58 (6.9%)
Hepatobiliary disorders
Hepatotoxicity	1/58 (1.7%)
Infections and infestations
Candidiasis	1/58 (1.7%)
Lung infection	2/58 (3.4%)
Sepsis	1/58 (1.7%)
Upper respiratory infection	1/58 (1.7%)
Urinary tract infection	2/58 (3.4%)
Investigations
Blood bilirrubin increase	1/58 (1.7%)
ALT increased	1/58 (1.7%)
GPT increased	1/58 (1.7%)
Metabolism and nutrition disorders
Hypercalcemia	1/58 (1.7%)
Hyperglycemia	1/58 (1.7%)
Hypokalemia	1/58 (1.7%)
Musculoskeletal and connective tissue disorders
Muscle weakness	1/58 (1.7%)
Nervous system disorders
Ataxia	1/58 (1.7%)
Cognitive disturbance	2/58 (3.4%)
Dizziness	1/58 (1.7%)
Dysphasia	1/58 (1.7%)
Headache	3/58 (5.2%)
Intracranial hemorrage	1/58 (1.7%)
Seizures	2/58 (3.4%)
somnolence	1/58 (1.7%)
Psychiatric disorders
Confusion	1/58 (1.7%)
Depression	1/58 (1.7%)
Reproductive system and breast disorders
Testicular disorder	1/58 (1.7%)
Respiratory, thoracic and mediastinal disorders
Pleural effussion	1/58 (1.7%)
Hemoptysis	1/58 (1.7%)
Vascular disorders
Thromboembolic event	2/58 (3.4%)
Other (Not Including Serious) Adverse Events
	Ipilimumab
	Affected / at Risk (%)	# Events
Total	57/58 (98.3%)
Blood and lymphatic system disorders
Edema	6/58 (10.3%)
Gastrointestinal disorders
Diarrhoea	14/58 (24.1%)
Nausea	16/58 (27.6%)
Vomiting	9/58 (15.5%)
General disorders
Fatigue	28/58 (48.3%)
Fever	7/58 (12.1%)
Metabolism and nutrition disorders
Anorexia	15/58 (25.9%)
Hyperglycemia	6/58 (10.3%)
Nervous system disorders
Dizziness	7/58 (12.1%)
Headache	23/58 (39.7%)
Skin and subcutaneous tissue disorders
Alopecia	9/58 (15.5%)
Pruritus	13/58 (22.4%)
Rash	5/58 (8.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.