A Phase 1 Study of OCV-C02 in Patients With Advanced or Relapsed Colorectal Cancer

• Sponsor: Otsuka Pharmaceutical Co., Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01801930
• Collaborator: (none)
• Enrollment: 24
• Locations: 3
• Arms: 4
• Duration (Months): 22
• Patients Per Site: 8
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

To assess the safety and tolerability of OCV-C02 in Patients With Advanced or Relapsed Colorectal Cancer Who Are Refractory or Intolerant to Standard Chemotherapy

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer	Drug: OCV-103 and OCV-104; Drug: OCV-103 and OCV-104; Drug: OCV-103 and OCV-104; Drug: OCV-103 and OCV-104	Phase 1

Detailed Description

The incidence of dose limiting toxicity (DLT) will be evaluated in cohorts of six patients by starting OCV-C02 administration at dose level 1 (OCV-103 and OCV-104 at 0.3 mg each), increasing the dose to dose level 2 (at 1 mg each), level 3 (at 3 mg each), and then up to dose level 4 (at 6 mg each). Once-weekly administration will be repeated four times in each treatment cycle, and the incidence of DLT from Day 1 to Day 29 will be evaluated.

At the end of Cycle 1, patients who wish to continue OCV-C02 treatment and have provided their written consent will be permitted to continue participation in the trial using the same dosing schedule for each subsequent cycle as that for Cycle 1.

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1 Study of OCV-C02 in Patients With Advanced or Relapsed Colorectal Cancer Who Are Refractory or Intolerant to Standard Chemotherapy
• Study Start Date: Mar 1, 2013
• Actual Primary Completion Date: Jan 1, 2015
• Actual Study Completion Date: Jan 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dose level 1	Drug: OCV-103 and OCV-104; 0.3 mg of each
Experimental: Dose level 2	Drug: OCV-103 and OCV-104; 1 mg of each
Experimental: Dose level 3	Drug: OCV-103 and OCV-104; 3 mg of each
Experimental: Dose level 4	Drug: OCV-103 and OCV-104; 6 mg of each

Outcome Measures

Primary Outcome Measures

1. Dose Limiting Toxicity (DLT) [Day 29]

   [Definition of DLT] Any of the following adverse events (AEs) that occurred by Day 29 of Cycle 1 and for which a causal relationship to OCV-C02 could not be ruled out: Grade 3 or higher non-hematological toxicities (except for injection site reaction and laboratory abnormalities lasting < 7 days without clinical symptoms) The following hematological toxicities: Grade 4 or higher anemia, Grade 4 or higher neutropenia or lymphocytopenia lasting 7 days, Grade 3 or higher febrile neutropenia, Grade 4 or higher platelet count decreased. The severity of AEs was graded in accordance with Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Japanese version). In addition, a DLT-equivalent treatment-emergent adverse event (TEAE) was defined as a DLT occurred during the extend treatment period (at Cycle 2 and thereafter).

Secondary Outcome Measures

1. Number of Subjects With CTCAE Grade 3 or Higher TEAEs [From the start of the study drug administration until the completion of the post-treatment observation (28 days after the last administration)]

   The severity (grade) of an AE was evaluated using the 5-point scale from Grade 1 to Grade 5 in accordance with CTCAE version 4.0 (Japanese version) , where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe or medically significant but not immediately life-threatening; Grade 4 = Life-threatening consequences; Grade 5 = Death related to AE.

2. Tumor Response Rate in Cycle 1 [Day 29]

   Tumor response was graded in accordance with the new Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Complete Response (CR): Disappearance of all target lesions (any malignant lymph nodes selected as target lesions must have a reduction in the minor axis to <10 mm) Partial Response (PR): At least a 30% decrease in the diameter sum of the target lesions as compared with the diameter sum at screening Progressive Disease (PD): At least a 20% increase in the diameter sum of the target lesions as compared with the smallest diameter sum recorded after the start of treatment, and at least 5 mm increase in the absolute increase of at least 5 mm Stable Disease (SD): Neither tumor shrinkage equivalent to PR nor tumor enlargement equivalent to PD Not Evaluable (NE): No examination is feasible or the tumor response cannot be considered as any of CR, PR, PD, and SD

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients who have human leukocyte antigen (HLA)-A*24:02

• Patients who have histologically-confirmed colorectal cancer (adenocarcinoma)

• Patients with advanced or relapsed colorectal cancer who are refractory or intolerant to standard chemotherapy

• Patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1 at the time of enrollment in the trial.

Exclusion Criteria:

• Patients who are HIV antibody test positive

• Patients with an active infection

• Patients who have or are suspected to have CNS metastasis of colon cancer (such as metastatis of the brain)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Nagoya		Japan
2		Sunto-gun		Japan
3		Tokyo		Japan

Sponsors and Collaborators

• Otsuka Pharmaceutical Co., Ltd.

Investigators

• Study Director: Junichi Hashimoto, PhD, Otsuka Pharmaceutical Co., Ltd.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Otsuka Pharmaceutical Co., Ltd.
• ClinicalTrials.gov Identifier: NCT01801930
• Other Study ID Numbers: 293-12-001; JapicCTI-132075
• First Posted: Mar 1, 2013
• Last Update Posted: Feb 26, 2021
• Last Verified: Feb 1, 2021

• Keywords provided by Otsuka Pharmaceutical Co., Ltd.: OCV-C02; Colorectal Cancer; Antigen specific cancer immunotherapeutic
• Additional relevant MeSH terms: Colorectal Neoplasms

Study Results

Participant Flow

Arm/Group Title	Dose Level 1	Dose Level 2	Dose Level 3	Dose Level 4
Arm/Group Description	OCV-103 and OCV-104 (0.3 mg of each) One cycle was defined as 28 days of treatment. Each subject received subcutaneous injections on Days 1, 8, 15, and 22 of each cycle.	OCV-103 and OCV-104 (1 mg of each) One cycle was defined as 28 days of treatment. Each subject received subcutaneous injections on Days 1, 8, 15, and 22 of each cycle.	OCV-103 and OCV-104 (3 mg of each) One cycle was defined as 28 days of treatment. Each subject received subcutaneous injections on Days 1, 8, 15, and 22 of each cycle.	OCV-103 and OCV-104 (6 mg of each) One cycle was defined as 28 days of treatment. Each subject received subcutaneous injections on Days 1, 8, 15, and 22 of each cycle.
Period Title: Overall Study
STARTED	6	6	6	6
COMPLETED	0	0	0	0
NOT COMPLETED	6	6	6	6

Baseline Characteristics

Arm/Group Title	Dose Level 1	Dose Level 2	Dose Level 3	Dose Level 4	Total
Arm/Group Description	OCV-103 and OCV-104 (0.3 mg of each) One cycle was defined as 28 days of treatment. Each subject received subcutaneous injections on Days 1, 8, 15, and 22 of each cycle.	OCV-103 and OCV-104 (1 mg of each) One cycle was defined as 28 days of treatment. Each subject received subcutaneous injections on Days 1, 8, 15, and 22 of each cycle.	OCV-103 and OCV-104 (3 mg of each) One cycle was defined as 28 days of treatment. Each subject received subcutaneous injections on Days 1, 8, 15, and 22 of each cycle.	OCV-103 and OCV-104 (6 mg of each) One cycle was defined as 28 days of treatment. Each subject received subcutaneous injections on Days 1, 8, 15, and 22 of each cycle.	Total of all reporting groups
Overall Participants	6	6	6	6	24
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	4 66.7%	5 83.3%	3 50%	3 50%	15 62.5%
>=65 years	2 33.3%	1 16.7%	3 50%	3 50%	9 37.5%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.8 (9.0)	54.8 (10.2)	65.8 (9.8)	63.3 (10.1)	60.7 (10.1)
Sex: Female, Male (Count of Participants)
Female	2 33.3%	1 16.7%	2 33.3%	3 50%	8 33.3%
Male	4 66.7%	5 83.3%	4 66.7%	3 50%	16 66.7%
Race/Ethnicity, Customized (Count of Participants)
Japanese	6 100%	6 100%	6 100%	6 100%	24 100%
Region of Enrollment (Count of Participants)
Japan	6 100%	6 100%	6 100%	6 100%	24 100%

Outcome Measures

1. Primary Outcome

Title	Dose Limiting Toxicity (DLT)
Description	[Definition of DLT] Any of the following adverse events (AEs) that occurred by Day 29 of Cycle 1 and for which a causal relationship to OCV-C02 could not be ruled out: Grade 3 or higher non-hematological toxicities (except for injection site reaction and laboratory abnormalities lasting < 7 days without clinical symptoms) The following hematological toxicities: Grade 4 or higher anemia, Grade 4 or higher neutropenia or lymphocytopenia lasting 7 days, Grade 3 or higher febrile neutropenia, Grade 4 or higher platelet count decreased. The severity of AEs was graded in accordance with Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Japanese version). In addition, a DLT-equivalent treatment-emergent adverse event (TEAE) was defined as a DLT occurred during the extend treatment period (at Cycle 2 and thereafter).
Time Frame	Day 29

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Level 1	Dose Level 2	Dose Level 3	Dose Level 4
Arm/Group Description	OCV-103 and OCV-104 (0.3 mg of each) One cycle was defined as 28 days of treatment. Each subject received subcutaneous injections on Days 1, 8, 15, and 22 of each cycle.	OCV-103 and OCV-104 (1 mg of each) One cycle was defined as 28 days of treatment. Each subject received subcutaneous injections on Days 1, 8, 15, and 22 of each cycle.	OCV-103 and OCV-104 (3 mg of each) One cycle was defined as 28 days of treatment. Each subject received subcutaneous injections on Days 1, 8, 15, and 22 of each cycle.	OCV-103 and OCV-104 (6 mg of each) One cycle was defined as 28 days of treatment. Each subject received subcutaneous injections on Days 1, 8, 15, and 22 of each cycle.
Measure Participants	6	6	6	6
Number [participants]	0 0%	0 0%	0 0%	0 0%

2. Secondary Outcome

Title	Number of Subjects With CTCAE Grade 3 or Higher TEAEs
Description	The severity (grade) of an AE was evaluated using the 5-point scale from Grade 1 to Grade 5 in accordance with CTCAE version 4.0 (Japanese version) , where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe or medically significant but not immediately life-threatening; Grade 4 = Life-threatening consequences; Grade 5 = Death related to AE.
Time Frame	From the start of the study drug administration until the completion of the post-treatment observation (28 days after the last administration)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Level 1	Dose Level 2	Dose Level 3	Dose Level 4
Arm/Group Description	OCV-103 and OCV-104 (0.3 mg of each) One cycle was defined as 28 days of treatment. Each subject received subcutaneous injections on Days 1, 8, 15, and 22 of each cycle.	OCV-103 and OCV-104 (1 mg of each) One cycle was defined as 28 days of treatment. Each subject received subcutaneous injections on Days 1, 8, 15, and 22 of each cycle.	OCV-103 and OCV-104 (3 mg of each) One cycle was defined as 28 days of treatment. Each subject received subcutaneous injections on Days 1, 8, 15, and 22 of each cycle.	OCV-103 and OCV-104 (6 mg of each) One cycle was defined as 28 days of treatment. Each subject received subcutaneous injections on Days 1, 8, 15, and 22 of each cycle.
Measure Participants	6	6	6	6
Number [participants]	3 50%	4 66.7%	1 16.7%	3 50%

3. Secondary Outcome

Title	Tumor Response Rate in Cycle 1
Description	Tumor response was graded in accordance with the new Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Complete Response (CR): Disappearance of all target lesions (any malignant lymph nodes selected as target lesions must have a reduction in the minor axis to <10 mm) Partial Response (PR): At least a 30% decrease in the diameter sum of the target lesions as compared with the diameter sum at screening Progressive Disease (PD): At least a 20% increase in the diameter sum of the target lesions as compared with the smallest diameter sum recorded after the start of treatment, and at least 5 mm increase in the absolute increase of at least 5 mm Stable Disease (SD): Neither tumor shrinkage equivalent to PR nor tumor enlargement equivalent to PD Not Evaluable (NE): No examination is feasible or the tumor response cannot be considered as any of CR, PR, PD, and SD
Time Frame	Day 29

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Level 1	Dose Level 2	Dose Level 3	Dose Level 4
Arm/Group Description	OCV-103 and OCV-104 (0.3 mg of each) One cycle was defined as 28 days of treatment. Each subject received subcutaneous injections on Days 1, 8, 15, and 22 of each cycle.	OCV-103 and OCV-104 (1 mg of each) One cycle was defined as 28 days of treatment. Each subject received subcutaneous injections on Days 1, 8, 15, and 22 of each cycle.	OCV-103 and OCV-104 (3 mg of each) One cycle was defined as 28 days of treatment. Each subject received subcutaneous injections on Days 1, 8, 15, and 22 of each cycle.	OCV-103 and OCV-104 (6 mg of each) One cycle was defined as 28 days of treatment. Each subject received subcutaneous injections on Days 1, 8, 15, and 22 of each cycle.
Measure Participants	6	6	6	6
CR	0 0%	0 0%	0 0%	0 0%
PR	0 0%	0 0%	0 0%	0 0%
SD	66.7 1111.7%	16.7 278.3%	83.3 1388.3%	66.7 1111.7%
PD	33.3 555%	83.3 1388.3%	16.7 278.3%	33.3 555%
NE	0 0%	0 0%	0 0%	0 0%

Adverse Events

Time Frame	TEAEs were collected from the start of the study drug administration until the completion of the post-treatment observation (28 days after the last administration)
Arm/Group Title	Dose Level 1		Dose Level 2		Dose Level 3		Dose Level 4
Arm/Group Description	OCV-103 and OCV-104 (0.3 mg of each) One cycle was defined as 28 days of treatment. Each subject received subcutaneous injections on Days 1, 8, 15, and 22 of each cycle.		OCV-103 and OCV-104 (1 mg of each) One cycle was defined as 28 days of treatment. Each subject received subcutaneous injections on Days 1, 8, 15, and 22 of each cycle.		OCV-103 and OCV-104 (3 mg of each) One cycle was defined as 28 days of treatment. Each subject received subcutaneous injections on Days 1, 8, 15, and 22 of each cycle.		OCV-103 and OCV-104 (6 mg of each) One cycle was defined as 28 days of treatment. Each subject received subcutaneous injections on Days 1, 8, 15, and 22 of each cycle.
All Cause Mortality
	Dose Level 1		Dose Level 2		Dose Level 3		Dose Level 4
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Serious Adverse Events
	Dose Level 1		Dose Level 2		Dose Level 3		Dose Level 4
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/6 (33.3%)		2/6 (33.3%)		1/6 (16.7%)		3/6 (50%)
Gastrointestinal disorders
Nausea	1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Vomiting	1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
General disorders
Gait disturbance	1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Pyrexia	0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)
Hepatobiliary disorders
Hepatic failure	0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
Bile duct stenosi	0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)
Infections and infestations
Lung infection	0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)
Metabolism and nutrition disorders
Hyperuricaemia	0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
Decreased appetite	1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain	1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Colorectal cancer	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		1/6 (16.7%)
Psychiatric disorders
Suicidal ideation	0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Dose Level 1		Dose Level 2		Dose Level 3		Dose Level 4
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/6 (100%)		6/6 (100%)		6/6 (100%)		6/6 (100%)
Blood and lymphatic system disorders
Anaemia	1/6 (16.7%)		0/6 (0%)		1/6 (16.7%)		1/6 (16.7%)
Gastrointestinal disorders
Abdominal distension	0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
Abdominal pain	0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)
Constipation	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		1/6 (16.7%)
Diarrhoea	0/6 (0%)		0/6 (0%)		0/6 (0%)		2/6 (33.3%)
Nausea	1/6 (16.7%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)
Vomiting	1/6 (16.7%)		0/6 (0%)		1/6 (16.7%)		2/6 (33.3%)
General disorders
Chills	0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)
Fatigue	0/6 (0%)		2/6 (33.3%)		0/6 (0%)		0/6 (0%)
Influenza like illness	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		1/6 (16.7%)
Injection site erythema	0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)
Injection site induration	0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)
Injection site reaction	1/6 (16.7%)		1/6 (16.7%)		3/6 (50%)		1/6 (16.7%)
Malaise	2/6 (33.3%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)
Oedema	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)
Pyrexia	1/6 (16.7%)		0/6 (0%)		2/6 (33.3%)		0/6 (0%)
Induration	0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)
Hepatobiliary disorders
Hepatic function abnormal	1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Hepatosplenomegaly	0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
Immune system disorders
Hypersensitivity	0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)
Infections and infestations
Bronchopneumonia	0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)
Infection	0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)
Nasopharyngitis	1/6 (16.7%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)
Tracheitis	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)
Urinary tract infection	0/6 (0%)		0/6 (0%)		0/6 (0%)		2/6 (33.3%)
Tinea infection	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)
Injury, poisoning and procedural complications
Excoriation	0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
Infusion related reaction	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)
Investigations
Alanine aminotransferase increased	1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Aspartate aminotransferase increased	1/6 (16.7%)		2/6 (33.3%)		0/6 (0%)		0/6 (0%)
Blood bilirubin increased	1/6 (16.7%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)
Blood creatinine increased	0/6 (0%)		2/6 (33.3%)		0/6 (0%)		0/6 (0%)
Blood lactate dehydrogenase increased	1/6 (16.7%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
Blood urea increased	0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
Eosinophil count increased	0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
Gamma-glutamyltransferase increased	0/6 (0%)		2/6 (33.3%)		0/6 (0%)		1/6 (16.7%)
Blood urine present	0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
Lymphocyte count decreased	0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
Blood alkaline phosphatase increased	1/6 (16.7%)		2/6 (33.3%)		0/6 (0%)		0/6 (0%)
Metabolism and nutrition disorders
Diabetes mellitus	0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
Hyperkalaemia	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)
Hypoalbuminaemia	1/6 (16.7%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)
Hypoglycaemia	0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
Hyponatraemia	0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
Decreased appetite	1/6 (16.7%)		1/6 (16.7%)		0/6 (0%)		2/6 (33.3%)
Musculoskeletal and connective tissue disorders
Back pain	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		2/6 (33.3%)
Musculoskeletal pain	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain	0/6 (0%)		2/6 (33.3%)		0/6 (0%)		0/6 (0%)
Nervous system disorders
Headache	1/6 (16.7%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)
Hypersomnia	0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)
Memory impairment	1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Brain oedema	2/6 (33.3%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Psychiatric disorders
Insomnia	1/6 (16.7%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)
Restlessness	0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
Renal and urinary disorders
Proteinuria	0/6 (0%)		2/6 (33.3%)		1/6 (16.7%)		0/6 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)
Dysphonia	1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Dyspnoea	0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
Pneumonia aspiration	0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)
Pulmonary haemorrhage	1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Upper respiratory tract inflammation	2/6 (33.3%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Skin and subcutaneous tissue disorders
Dry skin	1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Eczema	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)
Erythema	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)
Palmar-plantar erythrodysaesthesia syndrome	1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Pruritus	0/6 (0%)		2/6 (33.3%)		0/6 (0%)		0/6 (0%)
Rash	1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Vascular disorders
Hypertension	0/6 (0%)		1/6 (16.7%)		2/6 (33.3%)		0/6 (0%)
Orthostatic hypotension	1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)

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.