Ofatumumab and Bortezomib in Treating Patients With Previously Untreated Waldenstrom Macroglobulinemia

• Sponsor: Roswell Park Cancer Institute (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01536067
• Collaborator: National Cancer Institute (NCI) (NIH), GlaxoSmithKline (Industry)
• Enrollment: 3
• Locations: 2
• Arm: 1
• Patients Per Site: 1.5

Study Details

Study Description

Brief Summary

This phase II trial studies how well giving ofatumumab together with bortezomib works in treating patients with previously untreated Waldenstrom macroglobulinemia. Monoclonal antibodies, such as ofatumumab and bortezomib, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving ofatumumab together with bortezomib may be a better way to block cancer growth

Condition or Disease	Intervention/Treatment	Phase
Waldenström Macroglobulinemia	Biological: ofatumumab; Drug: bortezomib; Other: laboratory biomarker analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. Determine overall response rate (complete response [CR] + partial response [PR] + minor response [MR]) of ofatumumab in combination with bortezomib.

SECONDARY OBJECTIVES:

1. Determine complete remission (CR) rate, near (n)CR rate, very good partial response (VGPR) rate and PR rate per new criteria.

2. Determine 5 year progression free survival (PFS). III. Determine time to progression and duration of response of ofatumumab in conjunction with bortezomib.

3. Determine safety of ofatumumab in combination with bortezomib. V. Conduct laboratory correlates.

OUTLINE:

INDUCTION PHASE: Patients receive ofatumumab intravenously (IV) on days 1, 8, and 15 and bortezomib subcutaneously (SC) on days 8 and 15. Beginning on course 2, patients receive ofatumumab IV on days 1 and 15 and bortezomib SC on days 1, 8, and 15. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE PHASE: Beginning 8 weeks after course 4 of induction phase, patients receive ofatumumab IV on day 1 and bortezomib SC on days 1, 8, and 15. Treatment repeats every 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, and then every 3 months for 5 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 3 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter Phase II Study of Ofatumumab and Bortezomib (OB) in Previously Untreated Patients With Waldenstrom Macroglobulinemia
• Study Start Date: Apr 1, 2012
• Actual Primary Completion Date: Apr 1, 2014

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (monoclonal antibody therapy) INDUCTION PHASE: Patients receive ofatumumab IV on days 1, 8, and 15 and bortezomib SC on days 8 and 15. Beginning on course 2, patients receive ofatumumab IV on days 1 and 15 and bortezomib SC on days 1, 8, and 15. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Beginning 8 weeks after course 4 of induction phase, patients receive ofatumumab IV on day 1 and bortezomib SC on days 1, 8, and 15. Treatment repeats every 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Biological: ofatumumab; Given IV; Other Names: Arzerra HuMax-CD20 ; Drug: bortezomib; Given SC; Other Names: LDP 341 MLN341 VELCADE ; Other: laboratory biomarker analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate (CR + PR + MR) of Ofatumumab in Combination With Bortezomib [Every 28 days]

   Assessed using the Consensus Panel recommendations from the Third International Workshop on Waldenstrom Macroglobulinemia.

Secondary Outcome Measures

1. Frequency of Complete Remission (CR) [Every 28 days]

2. Frequency of Near (n)CR [Every 28 days]

3. Frequency of Very Good Partial Response (VGPR) [Every 28 days]

4. Frequency of PR [Every 28 days]

5. Time to Progression [From start of treatment to disease progression, assessed up to 12 months]

6. Progression-free Survival [From start of treatment to disease progression or death (regardless of the cause of death), whichever comes first, assessed up to 12 months]

7. Duration of Response [From the observation of a response to the time of disease progression, assessed up to 12 months]

8. Frequency and Severity of Toxicity as Graded According to the Cancer Therapeutic Evaluation Program (CTEP) Common Toxicity Criteria (CTC) Version 4.0 [Every 30 days for 2 months]

   Maximum grade per participant of any AE.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Diagnosis of Waldenstrom Macroglobulinemia and presence of cluster of differentiation (CD)20+ tumor cells as determined by immune-histochemistry or flow cytometric analysis in bone marrow or representative lymphoid tissue specimen; to be deemed eligible, patients must meet at least one of the following criteria:

• Rising immunoglobulin (Ig)M

• Hemoglobin =< 10 g/dL

• Platelet count =< 100 x 10^9/L

• Symptomatic or bulky lymphadenopathy or organomegaly

• Systemic manifestations of Waldenstrom Macroglobulinemia (WM), such as hyperviscosity symptoms (patients with symptoms of hyperviscosity syndrome must be treated with plasmapheresis to control the syndrome prior to enrollment), neuropathy, amyloidosis, cryoglobulinemia, B-symptoms, or recurrent bleeding

• Must have a measurable disease as defined by the monoclonal IgM level of 1 g/dL on serum protein electrophoresis (SPEP); if the level of IgM on SPEP is less than 1 g/dL in patients who meet any criteria in inclusion criteria 2, then the IgM level obtained from nephelometric measurement may be used to justify this criterion

• Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of =< 2

• Have a life expectancy of >= 3 months

• Absolute neutrophil count >= 1.0 x 10^9/L unless the result of disease infiltration of bone marrow

• Platelet count >= 50 x 10^9/L unless the result of disease infiltration of bone marrow

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x the institutional upper limit of normal (ULN)

• Total bilirubin =< 3 mg/dL or 1.5 x institutional ULN, whichever is lower

• Serum creatinine =< 3 mg/dL

• Female patients are either post-menopausal or surgically sterilized otherwise they must agree to use acceptable contraceptive methods (e.g. double barrier) during treatment

• Male subjects, even if surgically sterilized (i.e., status post vasectomy) must agree to one of the following:

• Practice effective barrier contraception during the entire study treatment period and through a minimum of 30 days after the last dose of study drug

• Completely abstain from heterosexual intercourse

• Patient or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent prior to receiving any study related procedure

Exclusion Criteria:

• Pregnant and nursing female patients

• Prior anti-neoplastic therapy for WM; the use of plasmapheresis to manage the symptoms of hyperviscosity and other IgM paraprotein mediated symptoms is allowed and does not disqualify a patient from the study; if a patient undergoes plasmapheresis within 8 weeks of starting the study treatment then the IgM level prior to plasmapheresis should be used for response assessment; neoplastic use of glucocorticoids is prohibited during the screening and treatment period; patients with active hyperviscosity symptoms should not be enrolled in this study unless the symptoms resolve after plasmapheresis

• Unwilling or unable to follow protocol requirements

• Any condition which in the Investigator's opinion deems the patient an unsuitable candidate to receive study drug

• Received an investigational agent within 30 days prior to enrollment

• Known human immunodeficiency virus (HIV) positive

• Positive serology for hepatitis B (HB) defined as a positive test for hepatitis B surface antigen (HBsAg); in addition, if HBsAg is negative and hepatitis B core antibody (HBcAb) is positive, regardless of hepatitis B surface antibody (HBsAb) status, a HB deoxyribonucleic acid test will be performed and if HB DNA is positive the patient will be excluded; if a patient is HBsAg negative, HBcAb positive, and HBsAb positive, indicating past but not active infection, the patient will be included on the study

• Positive serology for hepatitis C (HC) defined as a positive test for Hep C by enzyme immunoassays (EIA), in which case reflexively perform a HC recombinant immunoblot assay (RIBA) on the same sample to confirm the result

• Diagnosis of a malignant disorder other than WM within 3 years of the study enrollment with the exception of completely resected non-melanoma skin cancer and successfully treated in-situ cancer

• Uncontrolled infection

• Hypersensitivity to bortezomib, boron, or mannitol

• Grade 2 or greater peripheral neuropathy; since WM is known to cause peripheral neuropathy (PN), if, in investigator's judgement, a patient has Grade 2 PN related to WM, then he/she can be enrolled onto the study; under no circumstances patient with greater than Grade 2 PN can be enrolled

• Myocardial infarction within 6 months of enrollment; New York Heart Association (NYHA) Class III or more heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias; arrhythmias requiring active therapy other than chronic stable atrial fibrillation; if a patient has an implanted cardiac pacemaker and is otherwise well can be enrolled onto this study after demonstrating normal ejection fraction and clearance from a cardiologist; at the time of screening any electrocardiographic abnormality has to be documented as not medically relevant by the investigator before the patient proceeds to the enrollment phase

• Any serious medical or psychiatric illness that may interfere with participation in the study

• Patients with symptoms of hyperviscosity syndrome will not be enrolled on the study until they undergo plasmapheresis that results in resolution of symptoms and optimal control of the syndrome

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
2	Weill Cornell Medical College	New York	New York	United States	10065

Sponsors and Collaborators

• Roswell Park Cancer Institute
• National Cancer Institute (NCI)
• GlaxoSmithKline

Investigators

• Principal Investigator: Seema Bhat, Roswell Park Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Roswell Park Cancer Institute
• ClinicalTrials.gov Identifier: NCT01536067
• Other Study ID Numbers: I 205011; NCI-2011-03816
• First Posted: Feb 20, 2012
• Last Update Posted: Jun 10, 2016
• Last Verified: May 1, 2016

• Additional relevant MeSH terms: Waldenstrom Macroglobulinemia; Bortezomib; Ofatumumab

Study Results

Participant Flow

Arm/Group Title	Treatment (Monoclonal Antibody Therapy)
Arm/Group Description	INDUCTION PHASE: Patients receive ofatumumab IV on days 1, 8, and 15 and bortezomib SC on days 8 and 15. Beginning on course 2, patients receive ofatumumab IV on days 1 and 15 and bortezomib SC on days 1, 8, and 15. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Beginning 8 weeks after course 4 of induction phase, patients receive ofatumumab IV on day 1 and bortezomib SC on days 1, 8, and 15. Treatment repeats every 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. ofatumumab: Given IV bortezomib: Given SC laboratory biomarker analysis: Correlative studies
Period Title: Overall Study
STARTED	3
COMPLETED	2
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Treatment (Monoclonal Antibody Therapy)
Arm/Group Description	INDUCTION PHASE: Patients receive ofatumumab IV on days 1, 8, and 15 and bortezomib SC on days 8 and 15. Beginning on course 2, patients receive ofatumumab IV on days 1 and 15 and bortezomib SC on days 1, 8, and 15. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Beginning 8 weeks after course 4 of induction phase, patients receive ofatumumab IV on day 1 and bortezomib SC on days 1, 8, and 15. Treatment repeats every 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. ofatumumab: Given IV bortezomib: Given SC laboratory biomarker analysis: Correlative studies
Overall Participants	3
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.5 (1.8)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	3 100%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate (CR + PR + MR) of Ofatumumab in Combination With Bortezomib
Description	Assessed using the Consensus Panel recommendations from the Third International Workshop on Waldenstrom Macroglobulinemia.
Time Frame	Every 28 days

Outcome Measure Data

Analysis Population Description

Due to the study's early termination and low accrual, data were not collected for this assessment.

Arm/Group Title	Treatment (Monoclonal Antibody Therapy)
Arm/Group Description	INDUCTION PHASE: Patients receive ofatumumab IV on days 1, 8, and 15 and bortezomib SC on days 8 and 15. Beginning on course 2, patients receive ofatumumab IV on days 1 and 15 and bortezomib SC on days 1, 8, and 15. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Beginning 8 weeks after course 4 of induction phase, patients receive ofatumumab IV on day 1 and bortezomib SC on days 1, 8, and 15. Treatment repeats every 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. ofatumumab: Given IV bortezomib: Given SC laboratory biomarker analysis: Correlative studies
Measure Participants	0

2. Secondary Outcome

Title	Frequency of Complete Remission (CR)
Time Frame	Every 28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Frequency of Near (n)CR
Time Frame	Every 28 days

Outcome Measure Data

Analysis Population Description

Due to the study's early termination and low accrual, data were not collected for this assessment.

Arm/Group Title	Treatment (Monoclonal Antibody Therapy)
Arm/Group Description	INDUCTION PHASE: Patients receive ofatumumab IV on days 1, 8, and 15 and bortezomib SC on days 8 and 15. Beginning on course 2, patients receive ofatumumab IV on days 1 and 15 and bortezomib SC on days 1, 8, and 15. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Beginning 8 weeks after course 4 of induction phase, patients receive ofatumumab IV on day 1 and bortezomib SC on days 1, 8, and 15. Treatment repeats every 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. ofatumumab: Given IV bortezomib: Given SC laboratory biomarker analysis: Correlative studies
Measure Participants	0

4. Secondary Outcome

Title	Frequency of Very Good Partial Response (VGPR)
Time Frame	Every 28 days

Outcome Measure Data

Analysis Population Description

Due to the study's early termination and low accrual, data were not collected for this assessment.

Arm/Group Title	Treatment (Monoclonal Antibody Therapy)
Arm/Group Description	INDUCTION PHASE: Patients receive ofatumumab IV on days 1, 8, and 15 and bortezomib SC on days 8 and 15. Beginning on course 2, patients receive ofatumumab IV on days 1 and 15 and bortezomib SC on days 1, 8, and 15. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Beginning 8 weeks after course 4 of induction phase, patients receive ofatumumab IV on day 1 and bortezomib SC on days 1, 8, and 15. Treatment repeats every 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. ofatumumab: Given IV bortezomib: Given SC laboratory biomarker analysis: Correlative studies
Measure Participants	0

5. Secondary Outcome

Title	Frequency of PR
Time Frame	Every 28 days

Outcome Measure Data

Analysis Population Description

Due to the study's early termination and low accrual, data were not collected for this assessment.

Arm/Group Title	Treatment (Monoclonal Antibody Therapy)
Arm/Group Description	INDUCTION PHASE: Patients receive ofatumumab IV on days 1, 8, and 15 and bortezomib SC on days 8 and 15. Beginning on course 2, patients receive ofatumumab IV on days 1 and 15 and bortezomib SC on days 1, 8, and 15. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Beginning 8 weeks after course 4 of induction phase, patients receive ofatumumab IV on day 1 and bortezomib SC on days 1, 8, and 15. Treatment repeats every 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. ofatumumab: Given IV bortezomib: Given SC laboratory biomarker analysis: Correlative studies
Measure Participants	0

6. Secondary Outcome

Title	Time to Progression
Time Frame	From start of treatment to disease progression, assessed up to 12 months

Outcome Measure Data

Analysis Population Description

Due to the study's early termination and low accrual, data were not collected for this assessment.

Arm/Group Title	Treatment (Monoclonal Antibody Therapy)
Arm/Group Description	INDUCTION PHASE: Patients receive ofatumumab IV on days 1, 8, and 15 and bortezomib SC on days 8 and 15. Beginning on course 2, patients receive ofatumumab IV on days 1 and 15 and bortezomib SC on days 1, 8, and 15. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Beginning 8 weeks after course 4 of induction phase, patients receive ofatumumab IV on day 1 and bortezomib SC on days 1, 8, and 15. Treatment repeats every 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. ofatumumab: Given IV bortezomib: Given SC laboratory biomarker analysis: Correlative studies
Measure Participants	0

7. Secondary Outcome

Title	Progression-free Survival
Time Frame	From start of treatment to disease progression or death (regardless of the cause of death), whichever comes first, assessed up to 12 months

Outcome Measure Data

Analysis Population Description

Due to the study's early termination and low accrual, data were not collected for this assessment.

Arm/Group Title	Treatment (Monoclonal Antibody Therapy)
Arm/Group Description	INDUCTION PHASE: Patients receive ofatumumab IV on days 1, 8, and 15 and bortezomib SC on days 8 and 15. Beginning on course 2, patients receive ofatumumab IV on days 1 and 15 and bortezomib SC on days 1, 8, and 15. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Beginning 8 weeks after course 4 of induction phase, patients receive ofatumumab IV on day 1 and bortezomib SC on days 1, 8, and 15. Treatment repeats every 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. ofatumumab: Given IV bortezomib: Given SC laboratory biomarker analysis: Correlative studies
Measure Participants	0

8. Secondary Outcome

Title	Duration of Response
Time Frame	From the observation of a response to the time of disease progression, assessed up to 12 months

Outcome Measure Data

Analysis Population Description

Due to the study's early termination and low accrual, data were not collected for this assessment.

Arm/Group Title	Treatment (Monoclonal Antibody Therapy)
Arm/Group Description	INDUCTION PHASE: Patients receive ofatumumab IV on days 1, 8, and 15 and bortezomib SC on days 8 and 15. Beginning on course 2, patients receive ofatumumab IV on days 1 and 15 and bortezomib SC on days 1, 8, and 15. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Beginning 8 weeks after course 4 of induction phase, patients receive ofatumumab IV on day 1 and bortezomib SC on days 1, 8, and 15. Treatment repeats every 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. ofatumumab: Given IV bortezomib: Given SC laboratory biomarker analysis: Correlative studies
Measure Participants	0

9. Secondary Outcome

Title	Frequency and Severity of Toxicity as Graded According to the Cancer Therapeutic Evaluation Program (CTEP) Common Toxicity Criteria (CTC) Version 4.0
Description	Maximum grade per participant of any AE.
Time Frame	Every 30 days for 2 months

Outcome Measure Data

Analysis Population Description

All treated and eligible patients

Arm/Group Title	Treatment (Monoclonal Antibody Therapy)
Arm/Group Description	INDUCTION PHASE: Patients receive ofatumumab IV on days 1, 8, and 15 and bortezomib SC on days 8 and 15. Beginning on course 2, patients receive ofatumumab IV on days 1 and 15 and bortezomib SC on days 1, 8, and 15. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Beginning 8 weeks after course 4 of induction phase, patients receive ofatumumab IV on day 1 and bortezomib SC on days 1, 8, and 15. Treatment repeats every 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. ofatumumab: Given IV bortezomib: Given SC laboratory biomarker analysis: Correlative studies
Measure Participants	3
Grade 1	0 0%
Grade 2	0 0%
Grade 3	3 100%

Adverse Events

Arm/Group Title	Treatment (Monoclonal Antibody Therapy)
Arm/Group Description	INDUCTION PHASE: Patients receive ofatumumab IV on days 1, 8, and 15 and bortezomib SC on days 8 and 15. Beginning on course 2, patients receive ofatumumab IV on days 1 and 15 and bortezomib SC on days 1, 8, and 15. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Beginning 8 weeks after course 4 of induction phase, patients receive ofatumumab IV on day 1 and bortezomib SC on days 1, 8, and 15. Treatment repeats every 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. ofatumumab: Given IV bortezomib: Given SC laboratory biomarker analysis: Correlative studies
All Cause Mortality
	Treatment (Monoclonal Antibody Therapy)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Monoclonal Antibody Therapy)
	Affected / at Risk (%)	# Events
Total	0/3 (0%)
Other (Not Including Serious) Adverse Events
	Treatment (Monoclonal Antibody Therapy)
	Affected / at Risk (%)	# Events
Total	3/3 (100%)
Blood and lymphatic system disorders
Lymphopenia	1/3 (33.3%)	1
Neutropenia	1/3 (33.3%)	2
Thrombocytopenia	1/3 (33.3%)	1
Eye disorders
Iritis	1/3 (33.3%)	1
Vision blurred	1/3 (33.3%)	1
Gastrointestinal disorders
Abdominal pain	1/3 (33.3%)	1
Constipation	1/3 (33.3%)	1
Dyspepsia	1/3 (33.3%)	1
Nausea	1/3 (33.3%)	1
Vomiting	1/3 (33.3%)	1
General disorders
Chills	2/3 (66.7%)	2
Fatigue	1/3 (33.3%)	2
Gait disturbance	1/3 (33.3%)	1
Infusion site rash	1/3 (33.3%)	1
Injection site erythema	1/3 (33.3%)	1
Injection site joint redness	1/3 (33.3%)	1
Non-cardiac chest pain	1/3 (33.3%)	1
Pyrexia	1/3 (33.3%)	1
Infections and infestations
Furuncle	1/3 (33.3%)	1
Upper respiratory tract infection	1/3 (33.3%)	1
Injury, poisoning and procedural complications
Fall	1/3 (33.3%)	1
Infusion related reaction	2/3 (66.7%)	5
Procedural pain	1/3 (33.3%)	1
Thermal burn	1/3 (33.3%)	1
Investigations
Lymphocyte count decreased	1/3 (33.3%)	4
Metabolism and nutrition disorders
Hypercalcaemia	1/3 (33.3%)	1
Hyperglycaemia	1/3 (33.3%)	1
Hypernatraemia	1/3 (33.3%)	1
Hyperuricaemia	1/3 (33.3%)	1
Hypocalcaemia	1/3 (33.3%)	1
Hypoglycaemia	1/3 (33.3%)	3
Hyponatraemia	1/3 (33.3%)	1
Musculoskeletal and connective tissue disorders
Muscle spasms	1/3 (33.3%)	1
Muscular weakness	1/3 (33.3%)	1
Pain in extremity	1/3 (33.3%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour flare	1/3 (33.3%)	1
Nervous system disorders
Dizziness	1/3 (33.3%)	2
Neuropathy peripheral	1/3 (33.3%)	1
Peroneal nerve palsy	1/3 (33.3%)	1
Presyncope	1/3 (33.3%)	1
Sensory loss	1/3 (33.3%)	1
Reproductive system and breast disorders
Scrotal swelling	1/3 (33.3%)	1
Respiratory, thoracic and mediastinal disorders
Cough	1/3 (33.3%)	1
Skin and subcutaneous tissue disorders
Acne	1/3 (33.3%)	1
Erythema	1/3 (33.3%)	1
Rash	1/3 (33.3%)	2
Vascular disorders
Flushing	1/3 (33.3%)	1
Hypotension	1/3 (33.3%)	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.