A Study of BBI608 in Combination With Temozolomide in Adult Patients With Recurrent or Progressed Glioblastoma

• Sponsor: Sumitomo Pharma Oncology, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02315534
• Collaborator: (none)
• Enrollment: 34
• Locations: 3
• Arms: 2
• Duration (Months): 51.8
• Patients Per Site: 11.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This is an open label, multi-center, phase 1 safety run-in and phase 2 study of BBI608 in combination with temozolomide in patients with recurrent or progressive glioblastoma who have not received prior bevacizumab therapy.

Condition or Disease	Intervention/Treatment	Phase
Glioblastoma	Drug: BBI608; Drug: Temozolomide	Phase 1/Phase 2

Detailed Description

In arm A, patients who are candidates for surgical resection will receive BBI608 as monotherapy prior to resection, followed by post-operative BBI608 administered in combination with temozolomide. In arm B, patients who are not candidates for surgical resection will receive BBI608 administered orally, daily, in combination with temozolomide.

In the phase 1/dose-limiting toxicity (DLT) cohort portion of this study, pharmacokinetics will be evaluated for both arms A and B. Pharmacodynamics will be evaluated in all patients who undergo surgical resection.

Study Design

• Study Type: Interventional
• Actual Enrollment: 34 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase Ib/II Clinical Study of BBI608 in Combination With Temozolomide for Adult Patients With Recurrent or Progressed Glioblastoma
• Study Start Date: Mar 1, 2015
• Actual Primary Completion Date: Oct 9, 2018
• Actual Study Completion Date: Jun 24, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A Patients for whom surgery is recommended as part of treatment for recurrent Glioblastoma.	Drug: BBI608; In arm A, BBI608 will be administered at the recommended Phase 2 dose (RP2D) twice daily for 7(±2) days prior to planned surgical resection or biopsy of recurrent GBM. Upon the clinical recovery of the patient and at a time between 15-28 days after surgery, BBI608 will be administered orally, daily, each day of a 28 day cycle in combination with temozolomide. In arm B, patients who are not candidates for surgical resection will receive BBI608 administered orally, daily, each day of a 28 day cycle at the RP2D in combination with temozolomide.; Other Names: Napabucasin BB608 BBI-608 ; Drug: Temozolomide; Temozolomide (TMZ) will be administered orally, once daily, at a dose of 150 mg/m^2 daily on days 1 through 5 of each 28-day study cycle. The dose of temozolomide can be increased to 200 mg/m^2 as per standard TMZ dosing guidelines for patients who complete at least one cycle at 150 mg/m^2.; Other Names: Temodar
Experimental: Arm B Patients for whom surgery is not recommended as part of the treatment for recurrent Glioblastoma.	Drug: BBI608; In arm A, BBI608 will be administered at the recommended Phase 2 dose (RP2D) twice daily for 7(±2) days prior to planned surgical resection or biopsy of recurrent GBM. Upon the clinical recovery of the patient and at a time between 15-28 days after surgery, BBI608 will be administered orally, daily, each day of a 28 day cycle in combination with temozolomide. In arm B, patients who are not candidates for surgical resection will receive BBI608 administered orally, daily, each day of a 28 day cycle at the RP2D in combination with temozolomide.; Other Names: Napabucasin BB608 BBI-608 ; Drug: Temozolomide; Temozolomide (TMZ) will be administered orally, once daily, at a dose of 150 mg/m^2 daily on days 1 through 5 of each 28-day study cycle. The dose of temozolomide can be increased to 200 mg/m^2 as per standard TMZ dosing guidelines for patients who complete at least one cycle at 150 mg/m^2.; Other Names: Temodar

Outcome Measures

Primary Outcome Measures

1. Dose-limiting Toxicities (DLTs) [28 days after first administration of combination treatment (BBI608+TMZ)]

   Number of patients who experienced a dose limiting toxicity following a dosing of BBI608

2. Progression Free Survival (PFS)-6 [From the time of exposure to study drug to first objective documentation of disease progression or death due to any cause, assessed up to 6 months]

   To assess the effect of BBI608 + temozolomide (TMZ) therapy defined as the percentage of patients who have survived without objective disease progression for at least 6 months after treatment per neuro-oncology (RANO) criteria who had evaluable disease at baseline. PFS-6 is defined as the percentage of patients who survived without objective disease progression per RANO criteria for at least 6 months after treatment.

Secondary Outcome Measures

1. Progression Free Survival (PFS)-12 [From the time of exposure to study drug to first objective documentation of disease progression or death due to any cause, up to 12 months]

   To assess the effect of BBI608 + temozolomide (TMZ) therapy defined as the percentage of patients who have survived without objective disease progression for at least 12 months after treatment per neuro-oncology (RANO) criteria who had evaluable disease at baseline. PFS-12 is defined as the percentage of patients who survived without objective disease progression per RANO criteria for at least 12 months after treatment.

2. Overall Survival (OS) [From the time of exposure to study drug to death from any cause. If patient discontinued study drug, they were assessed the first 3 months after discontinuation, then every 3 months up to 1 year, then every 6 months thereafter until death.]

   To assess the effect of BBI608 + temozolomide (TMZ) on the overall survival of patients with recurrent or progressive glioblastoma multiforme (GBM) who had not received prior treatment with bevacizumab or other anti-vascular endothelial growth factor agents who either were eligible or not eligible for surgical resection.

3. Disease Control Rate (DCR) [4 weeks]

   To assess the percentage of patients that had evaluable disease at baseline with a documented complete response, partial response, and stable disease (CR + PR + SD) based on the Response Assessment in Neuro-Oncology (RANO) criteria out of all patients who received at least one dose of any study drug and had evaluable disease at baseline.

4. Overall Response Rate (ORR) [4 weeks]

   The proportion of patients with a documented complete response and partial response (CR + PR) based on RANO criteria.

5. Pharmacokinetic Profile of BBI608 and Temozolomide When Administered in Combination With Temozolomide as Assessed by the Area Under the Curve [On Day 1 and Day 5 after the first dosing, prior to dosing and 1, 2, 3, 5, 5h40m (day 1 only), 6, 7, 8 and 24 hours after first dose of BBI608]

   The area under the curve of BBI608, from time 0 to the last quantifiable concentration, calculated by a combination of linear and logarithmic trapezoidal methods (linear up/log down method)

6. Pharmacodynamic Activity of BBI608 When Administered in Combination With Temozolomide as Assessed by Tumor Biopsy and Cancer Stem Cell Assays as Well as the Concentration of Study Drug in Tumors [At the time of surgical resection]

   Tumor samples to provide information of the biomarkers by histopathology and Cancer Stem Cell assays as well as the concentration of study drug in tumors.

Eligibility Criteria

Criteria

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

Major Eligibility Criteria

1. Signed written informed consent must be obtained and documented according to International Conference on Harmonisation (ICH) and local regulatory requirements.

2. A histologically confirmed supratentorial glioblastoma (GBM) at first recurrence/progression (except for transformation from previous low grade glioma) following standard front-line therapy, for which treatment with temozolomide (TMZ) would be acceptable as determined by the Investigator

3. Previously received standard front-line GBM treatment including maximal surgical resection followed by external beam radiation therapy.

4. Patients may or may not be candidates for repeat surgical resection of the recurrent/progressed GBM.

5. Patients must have unequivocal evidence of tumor recurrence/progression by MRI at a minimum of 12 weeks following completion of chemoradiation or radiation therapy.

6. Patients must have measurable or non-measurable disease by response assessment in neuro-oncology Response Assessment in Neuro-oncology (RANO) criteria

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Laura and Isaac Perlmutter Cancer Center	New York	New York	United States	10016
2	University of Calgary	Calgary	Alberta	Canada
3	Princess Margaret Cancer Centre	Toronto	Ontario	Canada

Sponsors and Collaborators

• Sumitomo Pharma Oncology, Inc.

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Mar 9, 2017
• Statistical Analysis Plan - Mar 6, 2019

More Information

Publications

None provided.

• Responsible Party: Sumitomo Pharma Oncology, Inc.
• ClinicalTrials.gov Identifier: NCT02315534
• Other Study ID Numbers: BBI608-251; BBI608-201GBM
• First Posted: Dec 12, 2014
• Last Update Posted: Apr 6, 2022
• Last Verified: Apr 1, 2022

• Keywords provided by Sumitomo Pharma Oncology, Inc.: GBM; Malignant Glioma
• Additional relevant MeSH terms: Glioblastoma; Temozolomide

Study Results

Participant Flow

Pre-assignment Detail	There are no pre-assignment details, study arm was determined at patient enrollment to the study

Arm/Group Title	Candidates Whom Surgery is Recommended.	Candidates Whom Surgery is Not Recommended.
Arm/Group Description	BBI608 will be administered at the recommended phase 2 dose (RP2D) twice daily for 7(±2) days prior to planned surgical resection or biopsy of recurrent GBM. Upon the clinical recovery of the patient and at a time between 15-28 days after surgery, BBI608 will be administered orally, daily, each day of a 28 day cycle in combination with temozolomide	Patients who are not candidates for surgical resection will receive BBI608 administered orally, daily, each day of a 28 day cycle at the recommended phase 2 dose (RP2D) in combination with temozolomide
Period Title: Overall Study
STARTED	4	30
Assessment of Dose-limiting Toxicity (DLT)	0	0
Off Treatment Due to Radiologic Disease Progression (PD)	2	20
Off Treatment Due to Clinically Unacceptable Toxicities	1	7
Off Treatment Due to Patient Request	1	2
Off Treatment Due to Clinical PD	0	1
COMPLETED	4	30
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Candidates Whom Surgery is Recommended.	Candidates Whom Surgery is Not Recommended	Total
Arm/Group Description	Candidates who were candidates for repeat surgical resection	Candidates who were not candidates for repeat surgical resection	Total of all reporting groups
Overall Participants	4	30	34
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.8 (10.14)	54.6 (15.54)	55.1 (14.95)
Sex: Female, Male (Count of Participants)
Female	2 50%	12 40%	14 41.2%
Male	2 50%	18 60%	20 58.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	26 86.7%	26 76.5%
Asian	0 0%	3 10%	3 8.8%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	1 3.3%	1 2.9%
White	4 100%	0 0%	4 11.8%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Smoking (Count of Participants)
Lifetime nonsmoker	3 75%	21 70%	24 70.6%
Current smoker	0 0%	2 6.7%	2 5.9%
Former smoker	1 25%	7 23.3%	8 23.5%
Weight (kilograms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms]	100.55 (26.345)	78.21 (16.170)	80.84 (13.608)
Height (centimeters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeters]	177.25 (7.411)	173.91 (9.896)	174.30 (9.605)

Outcome Measures

1. Primary Outcome

Title	Dose-limiting Toxicities (DLTs)
Description	Number of patients who experienced a dose limiting toxicity following a dosing of BBI608
Time Frame	28 days after first administration of combination treatment (BBI608+TMZ)

Outcome Measure Data

Analysis Population Description

Up to the first 6 patients whom surgery was and wasn't recommended that received 28 days of continuous daily administration of BBI608 in combination with TMZ. Patients also had to be≥ 80% compliant to assigned dose to qualify for DLT analysis.

Arm/Group Title	Candidates Whom Surgery is Recommended.	Candidates Whom Surgery is Not Recommended
Arm/Group Description	The first 6 patients whom surgery was recommended that received 28 days of continuous daily administration of BBI608 in combination with TMZ. Patients also had to be ≥ 80% compliant to assigned dose to qualify for DLT analysis.	The first 6 patients whom surgery was not recommended that received 28 days of continuous daily administration of BBI608 in combination with TMZ. Patients also had to be ≥ 80% compliant to assigned dose to qualify for DLT analysis.
Measure Participants	4	6
Count of Participants [Participants]	0 0%	0 0%

2. Primary Outcome

Title	Progression Free Survival (PFS)-6
Description	To assess the effect of BBI608 + temozolomide (TMZ) therapy defined as the percentage of patients who have survived without objective disease progression for at least 6 months after treatment per neuro-oncology (RANO) criteria who had evaluable disease at baseline. PFS-6 is defined as the percentage of patients who survived without objective disease progression per RANO criteria for at least 6 months after treatment.
Time Frame	From the time of exposure to study drug to first objective documentation of disease progression or death due to any cause, assessed up to 6 months

Outcome Measure Data

Analysis Population Description

Data was only collected and analyzed for arms that enrolled at least 10 evaluable patients.

Arm/Group Title	Candidates Whom Surgery is Not Recommended.	Candidates Whom Surgery is Recommended.
Arm/Group Description	Participants who were not recommended for surgery that had evaluable disease at baseline and received at least 28 days of study drug (BBI608) in combination with temozolomide (TMZ). Data was only collected and analyzed for arms that enrolled at least 10 evaluable patients.	Participants who were recommended for surgery that had evaluable disease at baseline and received at least 28 days of study drug (BBI608) in combination with temozolomide (TMZ). Data was only collected and analyzed for arms that enrolled at least 10 evaluable patients.
Measure Participants	30	0
Number (80% Confidence Interval) [percentage of participants]	28.07 701.8%

3. Secondary Outcome

Title	Progression Free Survival (PFS)-12
Description	To assess the effect of BBI608 + temozolomide (TMZ) therapy defined as the percentage of patients who have survived without objective disease progression for at least 12 months after treatment per neuro-oncology (RANO) criteria who had evaluable disease at baseline. PFS-12 is defined as the percentage of patients who survived without objective disease progression per RANO criteria for at least 12 months after treatment.
Time Frame	From the time of exposure to study drug to first objective documentation of disease progression or death due to any cause, up to 12 months

Outcome Measure Data

Analysis Population Description

Data was only collected and analyzed for arms that enrolled at least 10 evaluable patients.

Arm/Group Title	Candidates Whom Surgery is Not Recommended	Candidates Whom Surgery is Recommended
Arm/Group Description	Participants who were not recommended for surgery that had evaluable disease at baseline and received at least 28 days of study drug (BBI608) in combination with temozolomide (TMZ). Data was only collected and analyzed for arms that enrolled at least 10 evaluable patients.	Participants who were recommended for surgery that had evaluable disease at baseline and received at least 28 days of study drug (BBI608) in combination with temozolomide (TMZ). Data was only collected and analyzed for arms that enrolled at least 10 evaluable patients.
Measure Participants	30	0
Number (80% Confidence Interval) [percentage of participants]	16.84 421%

4. Secondary Outcome

Title	Overall Survival (OS)
Description	To assess the effect of BBI608 + temozolomide (TMZ) on the overall survival of patients with recurrent or progressive glioblastoma multiforme (GBM) who had not received prior treatment with bevacizumab or other anti-vascular endothelial growth factor agents who either were eligible or not eligible for surgical resection.
Time Frame	From the time of exposure to study drug to death from any cause. If patient discontinued study drug, they were assessed the first 3 months after discontinuation, then every 3 months up to 1 year, then every 6 months thereafter until death.

Outcome Measure Data

Analysis Population Description

Data was only collected and analyzed for arms that enrolled at least 10 evaluable patients.

Arm/Group Title	Candidates Whom Surgery is Not Recommended	Candidates Whom Surgery is Recommended
Arm/Group Description	Participants who were not recommended for surgery that had evaluable disease at baseline and received at least 28 days of study drug (BBI608) in combination with temozolomide (TMZ). Data was only collected and analyzed for arms that enrolled at least 10 evaluable patients.	Participants who were recommended for surgery that had evaluable disease at baseline and received at least 28 days of study drug (BBI608) in combination with temozolomide (TMZ). Data was only collected and analyzed for arms that enrolled at least 10 evaluable patients.
Measure Participants	30	0
Median (95% Confidence Interval) [months]	8.05

5. Secondary Outcome

Title	Disease Control Rate (DCR)
Description	To assess the percentage of patients that had evaluable disease at baseline with a documented complete response, partial response, and stable disease (CR + PR + SD) based on the Response Assessment in Neuro-Oncology (RANO) criteria out of all patients who received at least one dose of any study drug and had evaluable disease at baseline.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

Data was only collected and analyzed for arms that enrolled at least 10 evaluable patients.

Arm/Group Title	Candidates Whom Surgery is Not Recommended	Candidates Whom Surgery is Recommended
Arm/Group Description	Participants who were not recommended for surgery that had evaluable disease at baseline and received at least 28 days of study drug (BBI608) in combination with temozolomide (TMZ). Data was only collected and analyzed for arms that enrolled at least 10 evaluable patients.	Participants who were recommended for surgery that had evaluable disease at baseline and received at least 28 days of study drug (BBI608) in combination with temozolomide (TMZ). Data was only collected and analyzed for arms that enrolled at least 10 evaluable patients.
Measure Participants	30	0
Number (95% Confidence Interval) [percentage of patients]	30

6. Secondary Outcome

Title	Overall Response Rate (ORR)
Description	The proportion of patients with a documented complete response and partial response (CR + PR) based on RANO criteria.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

Data was only collected and analyzed for arms that enrolled at least 10 evaluable patients.

Arm/Group Title	Candidates Whom Surgery is Not Recommended	Candidates Whom Surgery is Recommended
Arm/Group Description	Participants who were not recommended for surgery that had evaluable disease at baseline and received at least 28 days of study drug (BBI608) in combination with temozolomide (TMZ). Data was only collected and analyzed for arms that enrolled at least 10 evaluable patients.	Participants who were recommended for surgery that had evaluable disease at baseline and received at least 28 days of study drug (BBI608) in combination with temozolomide (TMZ). Data was only collected and analyzed for arms that enrolled at least 10 evaluable patients.
Measure Participants	30	0
Number (95% Confidence Interval) [percentage]	3

7. Secondary Outcome

Title	Pharmacokinetic Profile of BBI608 and Temozolomide When Administered in Combination With Temozolomide as Assessed by the Area Under the Curve
Description	The area under the curve of BBI608, from time 0 to the last quantifiable concentration, calculated by a combination of linear and logarithmic trapezoidal methods (linear up/log down method)
Time Frame	On Day 1 and Day 5 after the first dosing, prior to dosing and 1, 2, 3, 5, 5h40m (day 1 only), 6, 7, 8 and 24 hours after first dose of BBI608

Outcome Measure Data

Analysis Population Description

Candidates for who surgery was and was not recommended that received at least one dose of study drug and had at least one quantifiable concentration.

Arm/Group Title	Candidates Whom Surgery is Recommended	Candidates Whom Surgery is Not Recommended
Arm/Group Description	Candidates whom surgery is recommended that received at least one dose of study drug and had at least one quantifiable concentration	Candidates for whom surgery was not recommended that received at least one dose of study drug and had at least one quantifiable concentration
Measure Participants	4	10
Geometric Mean (Geometric Coefficient of Variation) [h*ng/ml]	4820 (19)	4200 (37.4)

8. Secondary Outcome

Title	Pharmacodynamic Activity of BBI608 When Administered in Combination With Temozolomide as Assessed by Tumor Biopsy and Cancer Stem Cell Assays as Well as the Concentration of Study Drug in Tumors
Description	Tumor samples to provide information of the biomarkers by histopathology and Cancer Stem Cell assays as well as the concentration of study drug in tumors.
Time Frame	At the time of surgical resection

Outcome Measure Data

Analysis Population Description

Candidates whom surgery is either recommended or nor recommended that received 28 days of study drug and provided tissue samples.

Arm/Group Title	Candidates Whom Surgery is Not Recommended	Candidates Whom Surgery is Recommended
Arm/Group Description	Candidates whom surgery is either recommended or not recommended that received 28 days of study drug and provided tissue samples	Candidates whom surgery is either recommended or not recommended that received 28 days of study drug and provided tissue samples
Measure Participants	23	0
pSTAT3+	19 475%
pSTAT3-	2 50%
Not Applicable	2 50%

Adverse Events

Time Frame	Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Arm/Group Title	Candidates Whom Surgery is Recommended		Candidates Whom Surgery is Not Recommended
Arm/Group Description	Participants whom surgery was recommended and received at least one dose of study medication (BBI608).		Patients who were not candidates for surgical resection and received at least one dose of study medication (BBI608).
All Cause Mortality
	Candidates Whom Surgery is Recommended		Candidates Whom Surgery is Not Recommended
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/4 (100%)		22/30 (73.3%)
Serious Adverse Events
	Candidates Whom Surgery is Recommended		Candidates Whom Surgery is Not Recommended
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/4 (75%)		5/30 (16.7%)
Gastrointestinal disorders
Diarrhoea	1/4 (25%)		1/30 (3.3%)
Vomiting	0/4 (0%)		1/30 (3.3%)
Colitis	0/4 (0%)		1/30 (3.3%)
General disorders
Fatigue	0/4 (0%)		1/30 (3.3%)
Infections and infestations
Cellulitis	1/4 (25%)		0/30 (0%)
Postoperative wound infection	1/4 (25%)		0/30 (0%)
Wound infection	1/4 (25%)		0/30 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour haemorrhage	1/4 (25%)		0/30 (0%)
Nervous system disorders
Pyramidal tract syndrome	0/4 (0%)		1/30 (3.3%)
Seizure	0/4 (0%)		1/30 (3.3%)
Cerebrospinal fluid leakage	2/4 (50%)		0/30 (0%)
Aphasia	1/4 (25%)		0/30 (0%)
Lethargy	1/4 (25%)		0/30 (0%)
Status epilepticus	1/4 (25%)		0/30 (0%)
Psychiatric disorders
Confusional state	1/4 (25%)		0/30 (0%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	2/4 (50%)		1/30 (3.3%)
Vascular disorders
Deep vein thrombosis	0/4 (0%)		1/30 (3.3%)
Other (Not Including Serious) Adverse Events
	Candidates Whom Surgery is Recommended		Candidates Whom Surgery is Not Recommended
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/4 (100%)		30/30 (100%)
Blood and lymphatic system disorders
Anaemia	1/4 (25%)		2/30 (6.7%)
Ear and labyrinth disorders
Ear pain	0/4 (0%)		2/30 (6.7%)
Gastrointestinal disorders
Diarrhoea	3/4 (75%)		27/30 (90%)
Abdominal pain	2/4 (50%)		21/30 (70%)
Nausea	1/4 (25%)		14/30 (46.7%)
Vomiting	1/4 (25%)		10/30 (33.3%)
Constipation	2/4 (50%)		5/30 (16.7%)
Dyspepsia	0/4 (0%)		3/30 (10%)
Haemorrhoidal haemorrhage	0/4 (0%)		2/30 (6.7%)
General disorders
Fatigue	4/4 (100%)		16/30 (53.3%)
Gait disturbance	1/4 (25%)		3/30 (10%)
Oedema peripheral	3/4 (75%)		0/30 (0%)
Infections and infestations
Nasopharyngitis	0/4 (0%)		2/30 (6.7%)
Injury, poisoning and procedural complications
Fall	0/4 (0%)		3/30 (10%)
Contusion	0/4 (0%)		2/30 (6.7%)
Investigations
Lymphocyte count decreased	0/4 (0%)		6/30 (20%)
Platelet count decreased	1/4 (25%)		6/30 (20%)
Weight decreased	1/4 (25%)		5/30 (16.7%)
Alanine aminotransferase increased	1/4 (25%)		4/30 (13.3%)
Neutrophil count decreased	0/4 (0%)		3/30 (10%)
Aspartate aminotransferase increased	0/4 (0%)		2/30 (6.7%)
Weight Increased	0/4 (0%)		2/30 (6.7%)
White blood cell count decreased	0/4 (0%)		2/30 (6.7%)
Metabolism and nutrition disorders
Decreased appetite	2/4 (50%)		6/30 (20%)
Dehydration	0/4 (0%)		2/30 (6.7%)
Hypoalbuminaemia	0/4 (0%)		2/30 (6.7%)
Hypokalaemia	0/4 (0%)		2/30 (6.7%)
Hyperglycaemia	2/4 (50%)		1/30 (3.3%)
Musculoskeletal and connective tissue disorders
Muscular weakness	0/4 (0%)		3/30 (10%)
Myalgia	0/4 (0%)		2/30 (6.7%)
Nervous system disorders
Headache	1/4 (25%)		10/30 (33.3%)
Pyramidal tract syndrome	1/4 (25%)		5/30 (16.7%)
Aphasia	2/4 (50%)		4/30 (13.3%)
Dysarthria	0/4 (0%)		4/30 (13.3%)
Hemiparesis	1/4 (25%)		4/30 (13.3%)
Cognitive disorder	1/4 (25%)		3/30 (10%)
Dizziness	0/4 (0%)		3/30 (10%)
Memory Impairment	0/4 (0%)		3/30 (10%)
Paraesthesia	0/4 (0%)		3/30 (10%)
Hemianopia homonymous	1/4 (25%)		2/30 (6.7%)
Seizure	1/4 (25%)		2/30 (6.7%)
Cerebrospinal fluid leakage	2/4 (50%)		0/30 (0%)
Psychiatric disorders
Confusional state	3/4 (75%)		2/30 (6.7%)
Renal and urinary disorders
Chromaturia	1/4 (25%)		4/30 (13.3%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	2/4 (50%)		0/30 (0%)
Pulmonary embolism	2/4 (50%)		1/30 (3.3%)
Vascular disorders
Hypotension	0/4 (0%)		2/30 (6.7%)

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 more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.