A Phase 1 Study of Mixed Bacteria Vaccine (MBV) in Patients With Tumors Expressing NY-ESO-1 Antigen

• Sponsor: Ludwig Institute for Cancer Research (Other)
• Overall Status: Completed
• CT.gov ID: NCT00623831
• Collaborator: Krankenhaus Nordwest (Other)
• Enrollment: 17
• Location: 1
• Arms: 2
• Duration (Months): 72
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This was a phase 1, open-label, multiple dose, single-arm study. The mixed bacteria vaccine (MBV) was administered at a starting dose of 250 EU (1 µL) and escalated in each subject to a dose inducing the desired pyrogenic effect, defined as a body temperature of 38°C to 39.5°C. The primary objective was to determine the safety profile of MBV in subjects with malignant tumors that expressed the NY-ESO-1 antigen and to identify the dose that induced the desired pyrogenic effect. Secondary objectives were to evaluate the immunological effects and tumor response of subjects following vaccination.

Condition or Disease	Intervention/Treatment	Phase
Melanoma; Sarcoma; Gastrointestinal Stromal Tumor (GIST); Head and Neck Cancer; Transitional Cell Carcinoma; Prostate Cancer; Ovarian Carcinoma; Esophageal Cancer; Breast Cancer	Biological: Mixed bacterial vaccine	Phase 1

Detailed Description

Subjects in Cohort 1 were enrolled to receive MBV subcutaneously at a starting dose of 250 EU (1 µL; dose level 1) administered twice weekly. In the absence of a dose-limiting toxicity (DLT), the MBV dose was escalated in each subject to the MBV dose that elicited the desired pyrogenic effect, or up to the maximum dose of 547,000 EU (dose level 8). Once the desired pyrogenic effect was observed, subjects received MBV twice weekly for 4 doses at the pyrogenic dose level.

Subjects in Cohort 2 were enrolled to receive MBV at the pyrogenic dose level (determined to be 60,800 EU [dose level 6]) twice weekly for 6 weeks. Vaccinations were injected intralesionally if possible and subcutaneously if intralesional injection was not possible. If a fever of 39.5°C to 40°C was observed, the subject's dose was reduced to dose level 5 (20,300 EU [81 μL]).

Subjects were observed at the clinic for up to 6 hours following each vaccination, with vital signs measured hourly. At baseline and throughout the study, subjects were assessed for NY-ESO-1-specific humoral and cellular immunity, chemistry, hematology, and cytokine analysis (interleukin [IL]-1, IL-6, interferon [IFN]-γ, and tumor necrosis factor [TNF]-α). Safety was monitored continuously throughout the study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 17 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1 Study of Mixed Bacteria Vaccine (MBV) in Patients With Tumors Expressing NY-ESO-1 Antigen.
• Study Start Date: May 1, 2007
• Actual Primary Completion Date: May 1, 2012
• Actual Study Completion Date: May 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 Subjects received MBV at a starting dose of 250 EU (dose level 1) twice weekly, with intrasubject dose escalations for each subsequent administration in the absence of a DLT until the desired pyrogenic effect was observed. The maximum possible dose to be investigated was 547,000 EU (dose level 8).	Biological: Mixed bacterial vaccine; MBV was administered twice weekly by subcutaneous injection in Cohort 1 and by intralesional (preferred) or subcutaneous (if intralesional not possible) injection in Cohort 2. In Cohort 1, the MBV starting dose was 250 EU (dose level 1) with possible intrasubject escalations up to 547,000 EU (dose level 8). In Cohort 2, all subjects received MBV at a fixed dose of 60,800 EU (dose level 6).; Other Names: MBV
Experimental: Cohort 2 Subjects received MBV twice weekly at the fixed dose (60,800 EU [dose level 6]) that was determined to be the pyrogenic dose level in Cohort 1.	Biological: Mixed bacterial vaccine; MBV was administered twice weekly by subcutaneous injection in Cohort 1 and by intralesional (preferred) or subcutaneous (if intralesional not possible) injection in Cohort 2. In Cohort 1, the MBV starting dose was 250 EU (dose level 1) with possible intrasubject escalations up to 547,000 EU (dose level 8). In Cohort 2, all subjects received MBV at a fixed dose of 60,800 EU (dose level 6).; Other Names: MBV

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Treatment-emergent Adverse Events (TEAEs) [Up to 3 months]

   Analysis of treatment-emergent adverse events (TEAEs) reported from clinical laboratory tests, physical examinations, and vital signs from pre-treatment through 4 weeks after the last dose of study treatment.

2. Number of Participants With Pyrogenicity at Each Dose Level Tested in the Intrasubject Dose Escalation Performed Over a Dose Range of 250 to 547,000 EU [Weeks 1 through 6]

   Intrasubject dose escalation performed over a dose range of 250 to 547,000 EU until achievement of the desired pyrogenic effects (i.e., body temperature increase to 38°C to 39.5°C). Of note, the median pyrogenic dose was 60,800 EU.

Secondary Outcome Measures

1. Number of Participants With Serum NY-ESO-1-specific Immune Responses [Up to 3 months]

   Serum NY-ESO-1-specific immune responses evaluated by humoral immunity (antibodies measured by ELISA), cellular immunity (CD8+ T-cell and CD4+ T-cell measured by ELISPOT), and cytokine activation (measured by ELISA) from pre-treatment through 4 weeks after the last dose of study treatment. [Note: CD = cluster of differentiation; IFN =interferon; IL = interleukin; TNF = tumor necrosis factor]

2. Number of Participants With Best Overall Tumor Response [Up to 3 months]

   Tumor responses evaluated using computed tomography and categorized according to RECIST version 1.0 at pre-treatment and 4 weeks after the last dose of study treatment. Per RECIST v1.0 for target lesions and assessed by MRI: Complete Response (CR): Disappearance of all target lesions [no evidence of disease]; Partial Response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD): ≥ 20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD): small changes that do not meet above criteria.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Histologically confirmed metastatic melanoma, head and neck cancer, transitional cell carcinoma, sarcoma, gastrointestinal stroma tumor (GIST) or prostate cancer.

2. Tumor expression of NY-ESO-1 by reverse transcriptase and polymerase chain reaction (RT-PCR) analysis, preferably, or immunohistochemistry.

3. Expected survival of at least 6 months.

4. Karnofsky performance status ≥ 70%.

5. Fully recovered from surgery.

6. Declined, intolerated or completed standard therapy defined as follows for each tumor entity:

7. Melanoma - resistance or intolerance to dacarbazine.

8. Sarcoma - resistance or intolerance to anthracyclines and to one platinum-containing chemotherapy regimen, no indication for irradiation.

9. GIST - failure or intolerance of imatinib and sunitinib.

10. Head and neck cancer - no indication for irradiation, resistance or intolerance to platinum-containing chemotherapy.

11. Transitional cell carcinoma - resistance or intolerance to cisplatin combined with gemcitabine.

12. Prostate cancer- failure of antihormonal treatment and resistance or intolerance to docetaxel.

13. Ovarian carcinoma - failure of standard chemotherapy consisting of a platinum agent combined with a taxane and of an anthracycline.

14. Esophageal cancer - failure of standard chemotherapy consisting of a platinum agent.

15. Breast cancer- failure or intolerance of standard first-, second- and third-line chemotherapy consisting of a taxane and anthracycline. No indication or resistance to standard antihormonal treatment. No indication or resistance to human epidermal growth factor receptor (HER)-2-neu targeted therapy. No indication or resistance to irradiation and/or surgery.

16. Within the last 2 weeks prior to study day 1, vital laboratory parameters must have been within the normal range, except for the following laboratory parameters, which must have been within the ranges specified:

• Absolute neutrophil count (ANC): ≥ 1,000/mm3

• Platelet count: ≥ 75,000/mm3

• Alanine aminotransferase (ALT): ≤ 5 x upper limit of normal (ULN)

• Aspartate aminotransferase (AST): ≤ 5 x ULN

• Total bilirubin: ≤ 2.5 x ULN

• Creatinine: ≤ 2 mg/dL

1. Age ≥ 18 years.

2. Able and willing to give written informed consent.

Exclusion Criteria:

1. Clinically significant heart disease (New York Heart Association Class III or IV).

2. Other serious illnesses, e.g., serious infections requiring antibiotics or bleeding disorders.

3. Subjects with serious intercurrent illness requiring hospitalization.

4. Known human immunodeficiency virus positivity.

5. Chemotherapy, radiation therapy or immunotherapy within 4 weeks prior to first dose of study agent (6 weeks for nitrosoureas).

6. Known autoimmune disease (rheumatoid arthritis, systemic lupus erythematosus), as these conditions might have interfered with the evaluation of the induced immune response. Subjects with vitiligo or melanoma-associated hypopigmentation were not excluded.

7. Chronic use of immunosuppressive drugs such as systemic corticosteroids.

8. Other malignancy within 3 years prior to entry into the study, except for treated non-melanoma skin cancer and cervical carcinoma in situ.

9. Mental impairment that may have compromised the ability to give informed consent and comply with the requirements of the study.

10. Lack of availability for immunological and clinical follow-up assessments.

11. Participation in any other clinical trial involving another investigational agent within 4 weeks prior to first dosing of study agent.

12. Pregnancy or breastfeeding.

13. Women of childbearing potential: Refusal or inability to use effective means of contraception.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Krankenhaus Nordwest	Frankfurt		Germany

Sponsors and Collaborators

• Ludwig Institute for Cancer Research
• Krankenhaus Nordwest

Investigators

• Principal Investigator: Elke Jager, MD, Krankenhaus Nordwest

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ludwig Institute for Cancer Research
• ClinicalTrials.gov Identifier: NCT00623831
• Other Study ID Numbers: LUD2005-003; 2006-002015-27
• First Posted: Feb 26, 2008
• Last Update Posted: Jan 9, 2017
• Last Verified: Nov 1, 2016

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Ludwig Institute for Cancer Research: MBV; Mixed Bacterial Vaccine; NY-ESO-1
• Additional relevant MeSH terms: Carcinoma; Gastrointestinal Stromal Tumors; Carcinoma, Transitional Cell

Study Results

Participant Flow

Arm/Group Title	Cohort 1	Cohort 2
Arm/Group Description	Subjects received MBV twice weekly by subcutaneous injection at a starting dose of 250 EU (dose level 1), with intrasubject dose escalations for each subsequent administration in the absence of a dose-limiting toxicity (DLT) until the desired pyrogenic effect was observed.	Subjects received MBV twice weekly by intralesional (preferred) or subcutaneous (if intralesional not possible) injection at the fixed dose (60,800 EU [dose level 6]) that was determined to be the pyrogenic dose level in Cohort 1.
Period Title: Overall Study
STARTED	13	4
COMPLETED	12	3
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	Cohort 1	Cohort 2	Total
Arm/Group Description	Subjects received MBV twice weekly by subcutaneous injection at a starting dose of 250 EU (dose level 1), with intrasubject dose escalations for each subsequent administration in the absence of a DLT until the desired pyrogenic effect was observed.	Subjects received MBV twice weekly by intralesional (preferred) or subcutaneous (if intralesional not possible) injection at the fixed dose (60,800 EU [dose level 6]) that was determined to be the pyrogenic dose level in Cohort 1.	Total of all reporting groups
Overall Participants	13	4	17
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	8 61.5%	3 75%	11 64.7%
>=65 years	5 38.5%	1 25%	6 35.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.0 (11.7)	55.5 (11.3)	57.4 (11.6)
Gender (Count of Participants)
Female	6 46.2%	2 50%	8 47.1%
Male	7 53.8%	2 50%	9 52.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	9 69.2%	4 100%	13 76.5%
Unknown or Not Reported	4 30.8%	0 0%	4 23.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	13 100%	4 100%	17 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
Germany	13 100%	4 100%	17 100%
Diagnosis at Study Entry (Count of Participants)
Melanoma	7 53.8%	2 50%	9 52.9%
Sarcoma	2 15.4%	1 25%	3 17.6%
Prostate cancer	2 15.4%	0 0%	2 11.8%
Head and neck cancer	1 7.7%	0 0%	1 5.9%
Breast cancer	0 0%	1 25%	1 5.9%
Transitional cell carcinoma	1 7.7%	0 0%	1 5.9%
Stage IV Disease at Study Entry (Count of Participants)
Count of Participants [Participants]	13 100%	4 100%	17 100%
Baseline Karnofsky Performance Status (Count of Participants)
70%	2 15.4%	0 0%	2 11.8%
80%	4 30.8%	0 0%	4 23.5%
90%	4 30.8%	0 0%	4 23.5%
100%	3 23.1%	4 100%	7 41.2%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Description	Analysis of treatment-emergent adverse events (TEAEs) reported from clinical laboratory tests, physical examinations, and vital signs from pre-treatment through 4 weeks after the last dose of study treatment.
Time Frame	Up to 3 months

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set comprises all subjects who received at least 1 dose of study drug.

Arm/Group Title	Cohort 1 (Safety Analysis Set)	Cohort 2 (Safety Analysis Set)
Arm/Group Description	Subjects received MBV twice weekly by subcutaneous injection at a starting dose of 250 EU (dose level 1), with intrasubject dose escalations for each subsequent administration in the absence of a DLT until the desired pyrogenic effect was observed.	Subjects received MBV twice weekly by intralesional (preferred) or subcutaneous (if intralesional not possible) injection at the fixed dose (60,800 EU [dose level 6]) that was determined to be the pyrogenic dose level in Cohort 1.
Measure Participants	13	4
Any TEAE	13 100%	4 100%
Grade 3 TEAE	3 23.1%	2 50%
Grade 4 TEAE	0 0%	0 0%
Grade 5 TEAE (Death)	1 7.7%	0 0%
Treatment-related TEAE	9 69.2%	3 75%
SAE	1 7.7%	1 25%
TEAE leading to withdrawal	0 0%	0 0%

2. Primary Outcome

Title	Number of Participants With Pyrogenicity at Each Dose Level Tested in the Intrasubject Dose Escalation Performed Over a Dose Range of 250 to 547,000 EU
Description	Intrasubject dose escalation performed over a dose range of 250 to 547,000 EU until achievement of the desired pyrogenic effects (i.e., body temperature increase to 38°C to 39.5°C). Of note, the median pyrogenic dose was 60,800 EU.
Time Frame	Weeks 1 through 6

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set comprises all subjects who received at least 1 dose of study drug.

Arm/Group Title	Cohort 1 (Safety Analysis Set)
Arm/Group Description	Subjects received MBV twice weekly by subcutaneous injection at a starting dose of 250 EU (dose level 1), with intrasubject dose escalations for each subsequent administration in the absence of a DLT until the desired pyrogenic effect was observed.
Measure Participants	13
Pyrogenic Dose: 250 EU	1 7.7%
Pyrogenic Dose: 750 EU	1 7.7%
Pyrogenic Dose: 2250 EU	1 7.7%
Pyrogenic Dose: 20,300 EU	1 7.7%
Pyrogenic Dose: 60,800 EU	2 15.4%
Pyrogenic Dose: 182,000 EU	2 15.4%
Pyrogenic Dose: 547,000 EU	3 23.1%
Desired Pyrogenic Effect Not Observed	1 7.7%
Discontinued Before Pyrogenic Effect Observed	1 7.7%

3. Secondary Outcome

Title	Number of Participants With Serum NY-ESO-1-specific Immune Responses
Description	Serum NY-ESO-1-specific immune responses evaluated by humoral immunity (antibodies measured by ELISA), cellular immunity (CD8+ T-cell and CD4+ T-cell measured by ELISPOT), and cytokine activation (measured by ELISA) from pre-treatment through 4 weeks after the last dose of study treatment. [Note: CD = cluster of differentiation; IFN =interferon; IL = interleukin; TNF = tumor necrosis factor]
Time Frame	Up to 3 months

Outcome Measure Data

Analysis Population Description

The Immune Response Analysis Set comprises all subjects who achieved the desired pyrogenic effects.

Arm/Group Title	Cohort 1 (Immune Response Analysis Set)
Arm/Group Description	Subjects received MBV twice weekly by subcutaneous injection at a starting dose of 250 EU (dose level 1), with intrasubject dose escalations for each subsequent administration in the absence of a DLT until the desired pyrogenic effect was observed.
Measure Participants	12
Antibody Sero(+) Pre- and Post-treatment	9 69.2%
Antibody Sero(-) Pre- and Post-treatment	2 15.4%
Antibody Sero(-) Pre-treatment, (+) Post-treatment	1 7.7%
CD4+ Pre- and Post-treatment	5 38.5%
CD4- Pre- and Post-treatment	6 46.2%
CD4 Not Evaluable	1 7.7%
CD8+ Pre- and Post-treatment	7 53.8%
CD8- Pre- and Post-treatment	5 38.5%
Increase of ≥ 2 Cytokines Post-treatment	11 84.6%
IL-6 Increase Post-treatment	11 84.6%
TNF-α Increase Post-treatment	5 38.5%
IFN-γ Increase Post-treatment	5 38.5%
IL-2 Increase Post-treatment	3 23.1%
IL-Iβ Increase Post-treatment	2 15.4%
IL-8 Increase Post-treatment	2 15.4%
IL-10 Increase Post-treatment	2 15.4%
IL-12 Increase Post-treatment	1 7.7%
IL-5 Increase Post-treatment	0 0%

4. Secondary Outcome

Title	Number of Participants With Best Overall Tumor Response
Description	Tumor responses evaluated using computed tomography and categorized according to RECIST version 1.0 at pre-treatment and 4 weeks after the last dose of study treatment. Per RECIST v1.0 for target lesions and assessed by MRI: Complete Response (CR): Disappearance of all target lesions [no evidence of disease]; Partial Response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD): ≥ 20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD): small changes that do not meet above criteria.
Time Frame	Up to 3 months

Outcome Measure Data

Analysis Population Description

The Tumor Response Analysis Set comprises all subjects who had an end-of-study tumor assessment performed.

Arm/Group Title	Cohort 1 (Tumor Response Analysis Set)	Cohort 2 (Tumor Response Analysis Set)
Arm/Group Description	Subjects received MBV twice weekly by subcutaneous injection at a starting dose of 250 EU (dose level 1), with intrasubject dose escalations for each subsequent administration in the absence of a DLT until the desired pyrogenic effect was observed.	Subjects received MBV twice weekly by intralesional (preferred) or subcutaneous (if intralesional not possible) injection at the fixed dose (60,800 EU [dose level 6]) that was determined to be the pyrogenic dose level in Cohort 1.
Measure Participants	12	3
No evidence of disease	2 15.4%	1 25%
Partial response	1 7.7%	0 0%
Stable disease	0 0%	1 25%
Progressive disease	9 69.2%	1 25%

Adverse Events

Time Frame	All AEs occurring between the signing of informed consent and the off-study date were documented, regardless of the causal relationship to study drug. AEs occurring after the first dose of study drug were considered treatment emergent (i.e., TEAEs). The AE reporting period for this study was up to 3 months for each subject.
Adverse Event Reporting Description	AE documentation included onset/resolution dates, severity using NCI CTCAE (v3.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Arm/Group Title	Cohort 1		Cohort 2
Arm/Group Description	Subjects received MBV twice weekly by subcutaneous injection at a starting dose of 250 EU (dose level 1), with intrasubject dose escalations for each subsequent administration in the absence of a DLT until the desired pyrogenic effect was observed.		Subjects received MBV twice weekly by intralesional (preferred) or subcutaneous (if intralesional not possible) injection at the fixed dose (60,800 EU [dose level 6]) that was determined to be the pyrogenic dose level in Cohort 1.
All Cause Mortality
	Cohort 1		Cohort 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Cohort 1		Cohort 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/13 (7.7%)		1/4 (25%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Rapid disease progression	1/13 (7.7%)		0/4 (0%)
Respiratory, thoracic and mediastinal disorders
Increased pleural effusion	0/13 (0%)		1/4 (25%)
Other (Not Including Serious) Adverse Events
	Cohort 1		Cohort 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/13 (100%)		4/4 (100%)
Blood and lymphatic system disorders
Anemia	2/13 (15.4%)		0/4 (0%)
Tumor-related thrombocytopenia	1/13 (7.7%)		0/4 (0%)
Cardiac disorders
Tachycardia	2/13 (15.4%)		1/4 (25%)
Bradycardia	1/13 (7.7%)		0/4 (0%)
Ear and labyrinth disorders
Vertigo	0/13 (0%)		2/4 (50%)
Eye disorders
Increased visual disturbance	1/13 (7.7%)		0/4 (0%)
Wound eye	1/13 (7.7%)		0/4 (0%)
Gastrointestinal disorders
Nausea	2/13 (15.4%)		1/4 (25%)
Constipation	1/13 (7.7%)		0/4 (0%)
Diarrhea	1/13 (7.7%)		0/4 (0%)
Heartburn	1/13 (7.7%)		0/4 (0%)
Increased swollen tongue	1/13 (7.7%)		0/4 (0%)
Pain upper abdomen	1/13 (7.7%)		0/4 (0%)
Soft stool	1/13 (7.7%)		0/4 (0%)
Symptomatic ascites	1/13 (7.7%)		0/4 (0%)
Vomiting	1/13 (7.7%)		0/4 (0%)
General disorders
Pain at injection site	4/13 (30.8%)		2/4 (50%)
Edema	4/13 (30.8%)		0/4 (0%)
Weakness	2/13 (15.4%)		2/4 (50%)
Chills	1/13 (7.7%)		2/4 (50%)
Fever	2/13 (15.4%)		1/4 (25%)
Fatigue	1/13 (7.7%)		1/4 (25%)
Flu-like feeling	1/13 (7.7%)		1/4 (25%)
Abrasion head	0/13 (0%)		1/4 (25%)
Angina tonsillaris	1/13 (7.7%)		0/4 (0%)
Co-reaction of prior injection sites	0/13 (0%)		1/4 (25%)
Expectoration	1/13 (7.7%)		0/4 (0%)
Increased pain	1/13 (7.7%)		0/4 (0%)
Mucositis	1/13 (7.7%)		0/4 (0%)
Pain (intermittent; face/head/tongue)	1/13 (7.7%)		0/4 (0%)
Pain at scar	1/13 (7.7%)		0/4 (0%)
Reduced performance status	1/13 (7.7%)		0/4 (0%)
Subjective feeling of sickness	1/13 (7.7%)		0/4 (0%)
Infections and infestations
Common cold	0/13 (0%)		1/4 (25%)
Herpes labialis	0/13 (0%)		1/4 (25%)
Infection	0/13 (0%)		1/4 (25%)
Infection at peg	1/13 (7.7%)		0/4 (0%)
Suspected candidosis glans penis	1/13 (7.7%)		0/4 (0%)
Thrush to the mouth	0/13 (0%)		1/4 (25%)
Injury, poisoning and procedural complications
Hematoma due to fall (by accident)	1/13 (7.7%)		0/4 (0%)
Investigations
CRP elevation	3/13 (23.1%)		2/4 (50%)
Metabolism and nutrition disorders
Hypokalemia	1/13 (7.7%)		0/4 (0%)
Inappetence	1/13 (7.7%)		0/4 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/13 (7.7%)		0/4 (0%)
Bone pain	1/13 (7.7%)		0/4 (0%)
Pain limbs	1/13 (7.7%)		0/4 (0%)
Pain right leg	1/13 (7.7%)		0/4 (0%)
Nervous system disorders
Feeling of pressure in head	0/13 (0%)		1/4 (25%)
Headache	1/13 (7.7%)		0/4 (0%)
Renal and urinary disorders
Bladder pressure	1/13 (7.7%)		0/4 (0%)
Candida infection urine	1/13 (7.7%)		0/4 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	0/13 (0%)		2/4 (50%)
Increased dyspnea	1/13 (7.7%)		1/4 (25%)
Epistaxis	1/13 (7.7%)		0/4 (0%)
Sore throat	0/13 (0%)		1/4 (25%)
Thoracic pain	1/13 (7.7%)		0/4 (0%)
Tickle in throat	1/13 (7.7%)		0/4 (0%)
Increased pleural effusion	1/13 (7.7%)		0/4 (0%)
Skin and subcutaneous tissue disorders
Decubitus	1/13 (7.7%)		0/4 (0%)
Pruritus at injection site	1/13 (7.7%)		0/4 (0%)
Reddening at port catheter site	1/13 (7.7%)		0/4 (0%)
Sweating	1/13 (7.7%)		0/4 (0%)
Vascular disorders
Hypertension	2/13 (15.4%)		1/4 (25%)
Hypotension	3/13 (23.1%)		0/4 (0%)
Reduced perfusion in toes	1/13 (7.7%)		0/4 (0%)
Thrombosis (pelvic)	1/13 (7.7%)		0/4 (0%)

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.