Recombinant Measles Virus Vaccine Therapy and Oncolytic Virus Therapy in Treating Patients With Progressive, Recurrent, or Refractory Ovarian Epithelial Cancer or Primary Peritoneal Cancer

• Sponsor: Mayo Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT00408590
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 37
• Location: 1
• Arm: 1
• Actual Duration (Months): 162.6
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

RATIONALE: A gene-modified virus may be able to kill tumor cells without damaging normal cells.

PURPOSE: This phase I trial is studying the side effects and best dose of an attenuated oncolytic measles virus therapy and oncolytic virus therapy in treating patients with progressive, recurrent, or refractory ovarian epithelial cancer or primary peritoneal cancer (measles virus vaccine therapy study closed as of 06/02/2008).

Condition or Disease	Intervention/Treatment	Phase
Ovarian Cancer; Primary Peritoneal Cavity Cancer	Biological: carcinoembryonic antigen-expressing measles virus; Biological: oncolytic measles virus encoding thyroidal sodium iodide symporter; Genetic: reverse transcriptase-polymerase chain reaction; Other: laboratory biomarker analysis	Phase 1

Detailed Description

OBJECTIVES:

• Determine the safety and toxicity of recombinant carcinoembryonic antigen (CEA)-expressing measles virus (MV-CEA) and oncolytic measles virus encoding thyroidal sodium iodide symporter (MV-NIS) in patients with progressive, recurrent, or refractory ovarian epithelial or primary peritoneal cavity cancer ( MV-CEA closed as of 06/02/2008).

• Determine the maximum-tolerated dose of MV-CEA and MV-NIS in these patients ( MV-CEA closed as of 06/02/2008).

• Characterize viral gene expression at each dose level as manifested by CEA titers in these patients.

• Assess viremia, viral replication, and measles virus shedding or persistence after study therapy.

• Determine humoral and cellular immune response to the injected virus in these patients.

• Assess, preliminarily, the antitumor efficacy of this therapy, by assessing CA-125 levels, radiographic response, and time to progression, in these patients.

• Determine the time course of viral gene expression and virus elimination and biodistribution of virally infected cells at various time points after infection with MV-NIS using single photon emission computed tomography (SPECT/CT) imaging.

• Assess viremia, viral replication, and measles virus shedding/persistence following intraperitoneal administration of MV-NIS.

OUTLINE: This is a dose-escalation study.

Patients receive recombinant carcinoembryonic antigen-expressing measles virus (MV-CEA) or oncolytic measles virus encoding thyroidal sodium iodide symporter (MV-NIS) intraperitoneally over 30 minutes on day 1. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity ( MV-CEA closed as of 06/02/2008).

Cohorts of 3-6 patients receive escalating doses of MV-CEA until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity ( MV-CEA closed as of 06/02/2008).

Peripheral blood mononuclear cells are collected at baseline and periodically during and after treatment to assess viremia. Throat gargle and urine specimens are assessed periodically during course 1 for viral shedding by reverse transcriptase-polymerase chain reaction (RT-PCR). Peritoneal aspirate is tested at baseline and periodically during treatment for viral replication by RT-PCR, co-culture with Vero cells, and measles virus N-specific mRNA in situ hybridization.

Patients may undergo single photon emission computed tomography (SPECT/CT) imaging at baseline and periodically during study.

After completion of study therapy, patients are followed periodically for up to 15 years.

PROJECTED ACCRUAL: A total of 46 patients will be accrued for this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 37 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I Trial of Intraperitoneal Administration of a) a CEA-Expressing Derivative, and b) a NIS-Expressing Derivative Manufactured From a Genetically Engineered Strain of Measles Virus in Patients With Recurrent Ovarian Cancer
• Actual Study Start Date: Apr 19, 2004
• Actual Primary Completion Date: Aug 1, 2012
• Actual Study Completion Date: Nov 7, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental Arm	Biological: carcinoembryonic antigen-expressing measles virus; Biological: oncolytic measles virus encoding thyroidal sodium iodide symporter; Genetic: reverse transcriptase-polymerase chain reaction; Other: laboratory biomarker analysis

Outcome Measures

Primary Outcome Measures

1. Dose Limiting Toxicity [up to 12 months after last treatment]

   If one patient experiences a Dose limiting Toxicity(DLT), up to three additional patients will be treated at the same dose level. If DLT is observed in only one of six patients treated at a given dose level, the next cohort of three patients will be treated at the next higher dose level. If two or more patients experience DLT at a particular dose level, then the dose escalation will cease and any subsequent patients will be treated at a lower dose level. Thus finding the Max tolerated dose

Secondary Outcome Measures

1. Number of Responses (Complete and Partial, Stable and Progressive Disease) [up to 12 months after last treatment]

   Responses will be summarized separately for the MV-CEA virus and MV-NIS virus by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease. CA125 levels and time to progression will also be summarized descriptively. Modified Response Evaluation Criteria in Solid Tumors(RECIST v1.0) criteria will be used. For target lesions: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter(LD) of target lesions; Progression (PD): As least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum LD

2. Change in CA-125 Levels From Baseline to Last Recorded Value (up to 18 Months) [baseline and up to 18 months]

   CA-125 tests are measured in units per milliliter (U/mL) and taken every cycle (up to 6-28 day cycles) during treatment and every three months up to 12 months after treatment. The change in CA-125 is calculated as the baseline CA-125 value subtracted by the last recorded value of CA-125 (up to 18 months from baseline.

3. Time to Progression [up to 12 months after last treatment]

   Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion criteria:

• Age ≥ 18 years.

• Must have persistent, recurrent or progressive ovarian cancer or primary peritoneal cancer after prior treatment with platinum and taxol compounds. Histologic confirmation of the original primary tumor is required. Prior bilateral oophorectomy is required.

• Patients with the following histologic epithelial cell types are eligible: Serous adenocarcinoma, endometroid adenocarcinoma, mucinous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, transitional cell carcinoma, malignant Brenner's Tumor, or adenocarcinoma NOS

• The following laboratory values obtained ≤7 days prior to registration:

• ANC ≥ 1500/μL

• PLT ≥ 100,000/μL

• Total bilirubin ≤ upper normal limit

• AST ≤ 2 x ULN

• Creatinine ≤ 1.5 x ULN

• Hgb ≥ 9.0 g/dL

• Ability to provide informed consent.

• Willingness to return to Mayo Clinic Rochester for follow-up.

• Life expectancy ≥ 12 weeks.

• Must have anti-measles immunity as demonstrated by serum IgG anti-measles antibody levels of ≥ 20.0 EU/ml as determined by Enzyme Immunoassay (Diamedix, FL).

• Must have normal serum CEA levels (<5 mg/ml) both at the time of study entry and in any prior testing. (NOTE: Not applicable for the MV-NIS cohort.)

• Willingness to provide all biologic specimens as required by the protocol.

• Measurable disease by exam or CT scan, or, for patients with CA-125 elevation or with microscopic residual but without measurable disease on imaging, willingness to undergo laparoscopy for evaluation of treatment effect if no radiographic progression after 6 treatment cycles.

• CD4 count ≥200/μL or ≥15% of peripheral blood lymphocytes

Exclusion criteria:

• Epithelial tumors of low malignant potential, stromal tumors, and germ cell tumors of the ovary.

• Known standard therapy for the patient's disease that is potentially curative or definitely capable of extending life expectancy. Subjects will be excluded if this is their first relapse and they have recurred >6 mo from completion of primary (adjuvant) chemotherapy.

• ECOG performance status (PS) 3 or 4.

• Active infection ≤5 days prior to registration.

• History of tuberculosis or history of PPD positivity.

• History of other malignancy ≤5 years except for non-melanoma skin cancer or carcinoma in situ of the cervix.

• Any of the following prior therapies:

• Chemotherapy ≤ 3 weeks prior to study entry

• Immunotherapy ≤ 4 weeks prior to study entry

• Biologic therapy ≤ 4 weeks prior to study entry

• Extensive abdominal surgery if it includes enterotomy(ies) <3 weeks prior to study entry. This criterion does not apply to placement of the peritoneal port-a-cath or lysis of adhesions at the time of study entry.

• Any viral or gene therapy prior to study entry

• Failure to fully recover from acute, reversible effects of prior chemotherapy regardless of interval since last treatment.

• New York Heart Association classification III or IV, known symptomatic coronary artery disease, or symptoms of coronary artery disease on systems review, or known cardiac arrhythmias (atrial fibrillation or SVT).

• Requiring blood product support.

• CNS metastases or seizure disorder.

• HIV-positive test result, or history of other immunodeficiency.

• History of organ transplantation.

• History of chronic hepatitis B or C.

• Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-FDA-approved indication and in the context of a research investigation).

• Any concurrent medications which could interfere with the trial.

• Intra-abdominal disease > 8 cm in diameter at the time of registration, intrahepatic disease, or disease beyond the abdominal cavity.

• Treatment with oral/systemic corticosteroids, with the exception of topical or inhaled steroids.

• Exposure to household contacts ≤15 months old or household contact with known immunodeficiency.

• Allergy to measles vaccine or history of severe reaction to prior measles vaccination.

• Allergy to iodine. This does not include reactions to intravenous contrast materials.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

• Mayo Clinic
• National Cancer Institute (NCI)

Investigators

• Study Chair: Evanthia Galanis, MD, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Mayo Clinic
• ClinicalTrials.gov Identifier: NCT00408590
• Other Study ID Numbers: CDR0000515008; P30CA015083; MC0117; 1260-03; NCI-2009-01199
• First Posted: Dec 7, 2006
• Last Update Posted: Mar 1, 2019
• Last Verified: Feb 1, 2019

• Keywords provided by Mayo Clinic: ovarian clear cell cystadenocarcinoma; ovarian endometrioid adenocarcinoma; primary peritoneal cavity cancer; ovarian mixed epithelial carcinoma; ovarian mucinous cystadenocarcinoma; ovarian serous cystadenocarcinoma; ovarian undifferentiated adenocarcinoma; recurrent ovarian epithelial cancer; Brenner tumor
• Additional relevant MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial

Study Results

Participant Flow

Arm/Group Title	Cohort 1, Dose Level 1	Cohort 1, Dose Level 2	Cohort 1, Dose Level 3	Cohort 1, Dose Level 4	Cohort 1, Dose Level 5	Cohort 1, Dose Level 6	Cohort 1, Dose Level 7	Cohort 2, Dose Level 1	Cohort 2, Dose Level 2
Arm/Group Description	Cohort 1 consists of the first 21 patients accrued to the study before addendum13. At dose level 1, these patients received a 10^3 TCID50dose of MV-CEA diluted in 500 ml of normal saline over 30 minutes. They receive treatment every 4 weeks for a total of 6 cycles.	Cohort 1 consists of the first 21 patients accrued to the study before addendum13. At dose level 2, these patients received a 10^4 TCID50dose of MV-CEA diluted in 500 ml of normal saline over 30 minutes. They receive treatment every 4 weeks for a total of 6 cycles.	Cohort 1 consists of the first 21 patients accrued to the study before addendum13. At dose level 3, these patients received a 10^5 TCID50dose of MV-CEA diluted in 500 ml of normal saline over 30 minutes. They receive treatment every 4 weeks for a total of 6 cycles.	Cohort 1 consists of the first 21 patients accrued to the study before addendum13. At dose level 4, these patients received a 10^6 TCID50dose of MV-CEA diluted in 500 ml of normal saline over 30 minutes. They receive treatment every 4 weeks for a total of 6 cycles.	Cohort 1 consists of the first 21 patients accrued to the study before addendum13. At dose level 5, these patients received a 10^7 TCID50dose of MV-CEA diluted in 500 ml of normal saline over 30 minutes. They receive treatment every 4 weeks for a total of 6 cycles.	Cohort 1 consists of the first 21 patients accrued to the study before addendum13. At dose level 6, these patients received a 10^8 TCID50dose of MV-CEA diluted in 500 ml of normal saline over 30 minutes. They receive treatment every 4 weeks for a total of 6 cycles.	Cohort 1 consists of the first 21 patients accrued to the study before addendum13. At dose level 7, these patients received a 10^9 TCID50dose of MV-CEA diluted in 500 ml of normal saline over 30 minutes. They receive treatment every 4 weeks for a total of 6 cycles.	Cohort 2 consists of the last 16 patients accrued to the study after addendum13. At dose level 1, these patients received one 0.025mg tablet of Cytomel 3 times a day for the 7 days leading up to a 10^8 TCID50 treatment of MV-NIS(every 4 weeks for up to 6 cycles). After this main treatment, they also received 5 mCi of Iodine, orally on days 3 and 8.	Cohort 2 consists of the last 16 patients accrued to the study after addendum13. At dose level 2, these patients received one 0.025mg tablet of Cytomel 3 times a day for the 7 days leading up to a 10^9 TCID50 treatment of MV-NIS(every 4 weeks for up to 6 cycles). After this main treatment, they also received 5 mCi of Iodine, orally on days 3 and 8.
Period Title: Overall Study
STARTED	3	3	3	3	3	3	3	3	13
COMPLETED	3	3	3	3	3	3	3	3	13
NOT COMPLETED	0	0	0	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Cohort 1	Cohort 2	Total
Arm/Group Description	Includes all dose levels of Cohort 1	Includes all dose levels of Cohort 2	Total of all reporting groups
Overall Participants	21	16	37
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	57	57.5	57
Sex: Female, Male (Count of Participants)
Female	21 100%	16 100%	37 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	21 100%	16 100%	37 100%
Ascites Present (participants with ascites) [Number]
Number [participants with ascites]	7 33.3%	13 81.3%	20 54.1%

Outcome Measures

1. Primary Outcome

Title	Dose Limiting Toxicity
Description	If one patient experiences a Dose limiting Toxicity(DLT), up to three additional patients will be treated at the same dose level. If DLT is observed in only one of six patients treated at a given dose level, the next cohort of three patients will be treated at the next higher dose level. If two or more patients experience DLT at a particular dose level, then the dose escalation will cease and any subsequent patients will be treated at a lower dose level. Thus finding the Max tolerated dose
Time Frame	up to 12 months after last treatment

Outcome Measure Data

Analysis Population Description

All patients that received study drug for at least 4 weeks were evaluated for dose limiting toxicities.

Arm/Group Title	Cohort 1	Cohort 2
Arm/Group Description	Includes all dose levels of Cohort 1	Includes all dose levels of Cohort 2
Measure Participants	21	16
Number [participants with DLTs]	0 0%	0 0%

2. Secondary Outcome

Title	Number of Responses (Complete and Partial, Stable and Progressive Disease)
Description	Responses will be summarized separately for the MV-CEA virus and MV-NIS virus by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease. CA125 levels and time to progression will also be summarized descriptively. Modified Response Evaluation Criteria in Solid Tumors(RECIST v1.0) criteria will be used. For target lesions: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter(LD) of target lesions; Progression (PD): As least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum LD
Time Frame	up to 12 months after last treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1	Cohort 2
Arm/Group Description	Includes all dose levels of Cohort 1	Includes all dose levels of Cohort 2
Measure Participants	21	16
CR	0 0%	0 0%
PR	0 0%	0 0%
SD	14 66.7%	13 81.3%
PD	7 33.3%	3 18.8%

3. Secondary Outcome

Title	Change in CA-125 Levels From Baseline to Last Recorded Value (up to 18 Months)
Description	CA-125 tests are measured in units per milliliter (U/mL) and taken every cycle (up to 6-28 day cycles) during treatment and every three months up to 12 months after treatment. The change in CA-125 is calculated as the baseline CA-125 value subtracted by the last recorded value of CA-125 (up to 18 months from baseline.
Time Frame	baseline and up to 18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1, Dose Level 1	Cohort 1, Dose Level 2	Cohort 1, Dose Level 3	Cohort 1, Dose Level 4	Cohort 1, Dose Level 5	Cohort 1, Dose Level 6	Cohort 1, Dose Level 7	Cohort 2, Dose Level 1	Cohort 2, Dose Level 2
Arm/Group Description	Cohort 1 consists of the first 21 patients accrued to the study before addendum13. At dose level 1, these patients received a 10^3 TCID50dose of MV-CEA diluted in 500 ml of normal saline over 30 minutes. They receive treatment every 4 weeks for a total of 6 cycles.	Cohort 1 consists of the first 21 patients accrued to the study before addendum13. At dose level 2, these patients received a 10^4 TCID50dose of MV-CEA diluted in 500 ml of normal saline over 30 minutes. They receive treatment every 4 weeks for a total of 6 cycles.	Cohort 1 consists of the first 21 patients accrued to the study before addendum13. At dose level 3, these patients received a 10^5 TCID50dose of MV-CEA diluted in 500 ml of normal saline over 30 minutes. They receive treatment every 4 weeks for a total of 6 cycles.	Cohort 1 consists of the first 21 patients accrued to the study before addendum13. At dose level 4, these patients received a 10^6 TCID50dose of MV-CEA diluted in 500 ml of normal saline over 30 minutes. They receive treatment every 4 weeks for a total of 6 cycles.	Cohort 1 consists of the first 21 patients accrued to the study before addendum13. At dose level 5, these patients received a 10^7 TCID50dose of MV-CEA diluted in 500 ml of normal saline over 30 minutes. They receive treatment every 4 weeks for a total of 6 cycles.	Cohort 1 consists of the first 21 patients accrued to the study before addendum13. At dose level 6, these patients received a 10^8 TCID50dose of MV-CEA diluted in 500 ml of normal saline over 30 minutes. They receive treatment every 4 weeks for a total of 6 cycles.	Cohort 1 consists of the first 21 patients accrued to the study before addendum13. At dose level 7, these patients received a 10^9 TCID50dose of MV-CEA diluted in 500 ml of normal saline over 30 minutes. They receive treatment every 4 weeks for a total of 6 cycles.	Cohort 2 consists of the last 16 patients accrued to the study after addendum13. At dose level 1, these patients received one 0.025mg tablet of Cytomel 3 times a day for the 7 days leading up to a 10^8 TCID50 treatment of MV-NIS(every 4 weeks for up to 6 cycles). After this main treatment, they also received 5 mCi of Iodine, orally on days 3 and 8.	Cohort 2 consists of the last 16 patients accrued to the study after addendum13. At dose level 2, these patients received one 0.025mg tablet of Cytomel 3 times a day for the 7 days leading up to a 10^9 TCID50 treatment of MV-NIS(every 4 weeks for up to 6 cycles). After this main treatment, they also received 5 mCi of Iodine, orally on days 3 and 8.
Measure Participants	3	1	3	2	3	3	3	3	13
Median (Full Range) [U/ml]	-20.2	97	52	42.5	129	-112	11	1200	18

4. Secondary Outcome

Title	Time to Progression
Description	Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time Frame	up to 12 months after last treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1	Cohort 2
Arm/Group Description	Includes all dose levels of Cohort 1	Includes all dose levels of Cohort 2
Measure Participants	21	16
Median (Full Range) [Days]	55	64.5

Adverse Events

Arm/Group Title	Cohort 1		Cohort 2
Arm/Group Description	Includes all dose levels of Cohort 1		Includes all dose levels of Cohort 2
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	3/21 (14.3%)		2/16 (12.5%)
Gastrointestinal disorders
Abdominal distension	1/21 (4.8%)	1	0/16 (0%)	0
Abdominal pain	1/21 (4.8%)	1	0/16 (0%)	0
Ascites	1/21 (4.8%)	1	0/16 (0%)	0
Colonic obstruction	0/21 (0%)	0	1/16 (6.3%)	1
Nausea	2/21 (9.5%)	2	0/16 (0%)	0
Small intestinal obstruction	2/21 (9.5%)	2	1/16 (6.3%)	1
Vomiting	2/21 (9.5%)	2	0/16 (0%)	0
General disorders
Edema limbs	1/21 (4.8%)	1	0/16 (0%)	0
Fatigue	1/21 (4.8%)	1	0/16 (0%)	0
Infections and infestations
Peritoneal infection	1/21 (4.8%)	1	0/16 (0%)	0
Skin infection	1/21 (4.8%)	1	0/16 (0%)	0
Investigations
Creatine phosphokinase increased	1/21 (4.8%)	1	0/16 (0%)	0
Creatinine increased	1/21 (4.8%)	1	0/16 (0%)	0
Metabolism and nutrition disorders
Anorexia	1/21 (4.8%)	1	0/16 (0%)	0
Dehydration	2/21 (9.5%)	3	0/16 (0%)	0
Vascular disorders
Hypotension	1/21 (4.8%)	1	0/16 (0%)	0
Thrombosis	1/21 (4.8%)	1	0/16 (0%)	0
Other (Not Including Serious) Adverse Events
	Cohort 1		Cohort 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/21 (100%)		16/16 (100%)
Blood and lymphatic system disorders
Hemoglobin decreased	6/21 (28.6%)	8	6/16 (37.5%)	12
Hemolysis	1/21 (4.8%)	1	0/16 (0%)	0
Cardiac disorders
Arrhythmia	1/21 (4.8%)	1	0/16 (0%)	0
Atrial tachycardia	0/21 (0%)	0	1/16 (6.3%)	1
Cardiac disorder	1/21 (4.8%)	1	0/16 (0%)	0
Palpitations	0/21 (0%)	0	1/16 (6.3%)	1
Sinus bradycardia	1/21 (4.8%)	6	0/16 (0%)	0
Sinus tachycardia	2/21 (9.5%)	3	2/16 (12.5%)	3
Ear and labyrinth disorders
Tinnitus	1/21 (4.8%)	1	0/16 (0%)	0
Endocrine disorders
Endocrine disorder	0/21 (0%)	0	1/16 (6.3%)	1
Eye disorders
Extraocular muscle paresis	1/21 (4.8%)	1	0/16 (0%)	0
Eye disorder	1/21 (4.8%)	2	0/16 (0%)	0
Gastrointestinal disorders
Abdominal distension	6/21 (28.6%)	9	7/16 (43.8%)	10
Abdominal pain	16/21 (76.2%)	36	16/16 (100%)	33
Ascites	1/21 (4.8%)	1	1/16 (6.3%)	1
Constipation	6/21 (28.6%)	9	6/16 (37.5%)	11
Diarrhea	11/21 (52.4%)	12	9/16 (56.3%)	15
Dyspepsia	0/21 (0%)	0	1/16 (6.3%)	2
Flatulence	8/21 (38.1%)	13	7/16 (43.8%)	14
Gastritis	2/21 (9.5%)	2	1/16 (6.3%)	1
Gastrointestinal disorder	0/21 (0%)	0	1/16 (6.3%)	1
Lower gastrointestinal hemorrhage	1/21 (4.8%)	1	0/16 (0%)	0
Mucositis oral	2/21 (9.5%)	3	1/16 (6.3%)	1
Nausea	9/21 (42.9%)	13	9/16 (56.3%)	13
Rectal hemorrhage	0/21 (0%)	0	1/16 (6.3%)	1
Small intestinal obstruction	1/21 (4.8%)	1	0/16 (0%)	0
Stomach pain	1/21 (4.8%)	1	0/16 (0%)	0
Vomiting	5/21 (23.8%)	6	8/16 (50%)	11
General disorders
Chest pain	0/21 (0%)	0	1/16 (6.3%)	1
Chills	4/21 (19%)	9	9/16 (56.3%)	20
Edema limbs	5/21 (23.8%)	9	4/16 (25%)	4
Fatigue	13/21 (61.9%)	26	10/16 (62.5%)	24
Fever	10/21 (47.6%)	16	10/16 (62.5%)	22
General symptom	1/21 (4.8%)	1	2/16 (12.5%)	3
Injection site reaction	1/21 (4.8%)	2	0/16 (0%)	0
Pain	7/21 (33.3%)	17	4/16 (25%)	5
Infections and infestations
Bladder infection	1/21 (4.8%)	1	1/16 (6.3%)	1
Bronchitis	0/21 (0%)	0	1/16 (6.3%)	1
Catheter related infection	0/21 (0%)	0	1/16 (6.3%)	1
Infection	1/21 (4.8%)	1	0/16 (0%)	0
Skin infection	1/21 (4.8%)	2	0/16 (0%)	0
Soft tissue infection	1/21 (4.8%)	1	0/16 (0%)	0
Wound infection	1/21 (4.8%)	1	0/16 (0%)	0
Injury, poisoning and procedural complications
Bruising	1/21 (4.8%)	1	0/16 (0%)	0
Intestinal stoma site bleeding	0/21 (0%)	0	1/16 (6.3%)	1
Investigations
Alanine aminotransferase increased	1/21 (4.8%)	3	1/16 (6.3%)	4
Alkaline phosphatase increased	1/21 (4.8%)	1	3/16 (18.8%)	5
Aspartate aminotransferase increased	3/21 (14.3%)	4	2/16 (12.5%)	3
Blood bilirubin increased	0/21 (0%)	0	1/16 (6.3%)	2
Creatinine increased	1/21 (4.8%)	1	2/16 (12.5%)	5
Laboratory test abnormal	0/21 (0%)	0	1/16 (6.3%)	2
Leukocyte count decreased	1/21 (4.8%)	3	4/16 (25%)	9
Lymphocyte count decreased	0/21 (0%)	0	1/16 (6.3%)	1
Neutrophil count decreased	1/21 (4.8%)	5	3/16 (18.8%)	6
Platelet count decreased	0/21 (0%)	0	3/16 (18.8%)	6
Serum cholesterol increased	0/21 (0%)	0	1/16 (6.3%)	1
Weight gain	0/21 (0%)	0	1/16 (6.3%)	4
Weight loss	1/21 (4.8%)	1	0/16 (0%)	0
Metabolism and nutrition disorders
Anorexia	9/21 (42.9%)	14	3/16 (18.8%)	4
Blood glucose increased	3/21 (14.3%)	7	3/16 (18.8%)	3
Dehydration	1/21 (4.8%)	1	0/16 (0%)	0
Serum albumin decreased	1/21 (4.8%)	1	0/16 (0%)	0
Serum calcium decreased	0/21 (0%)	0	1/16 (6.3%)	1
Serum calcium increased	0/21 (0%)	0	1/16 (6.3%)	2
Serum glucose decreased	0/21 (0%)	0	1/16 (6.3%)	1
Serum phosphate decreased	0/21 (0%)	0	1/16 (6.3%)	1
Serum potassium decreased	0/21 (0%)	0	1/16 (6.3%)	1
Serum potassium increased	5/21 (23.8%)	5	0/16 (0%)	0
Serum sodium decreased	2/21 (9.5%)	2	3/16 (18.8%)	4
Musculoskeletal and connective tissue disorders
Arthralgia	2/21 (9.5%)	11	1/16 (6.3%)	1
Back pain	5/21 (23.8%)	9	0/16 (0%)	0
Bone pain	2/21 (9.5%)	2	1/16 (6.3%)	1
Myalgia	4/21 (19%)	11	1/16 (6.3%)	2
Pain in extremity	1/21 (4.8%)	1	0/16 (0%)	0
Nervous system disorders
Dizziness	2/21 (9.5%)	2	0/16 (0%)	0
Headache	5/21 (23.8%)	5	3/16 (18.8%)	6
Neurological disorder NOS	2/21 (9.5%)	2	1/16 (6.3%)	1
Peripheral motor neuropathy	1/21 (4.8%)	2	1/16 (6.3%)	1
Peripheral sensory neuropathy	1/21 (4.8%)	1	3/16 (18.8%)	7
Speech disorder	1/21 (4.8%)	1	1/16 (6.3%)	1
Syncope vasovagal	1/21 (4.8%)	1	0/16 (0%)	0
Psychiatric disorders
Anxiety	1/21 (4.8%)	1	2/16 (12.5%)	3
Depression	1/21 (4.8%)	1	0/16 (0%)	0
Insomnia	3/21 (14.3%)	3	1/16 (6.3%)	2
Renal and urinary disorders
Renal failure	1/21 (4.8%)	1	0/16 (0%)	0
Urogenital disorder	0/21 (0%)	0	1/16 (6.3%)	2
Reproductive system and breast disorders
Pelvic pain	0/21 (0%)	0	1/16 (6.3%)	2
Vaginal discharge	0/21 (0%)	0	2/16 (12.5%)	3
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	1/21 (4.8%)	1	1/16 (6.3%)	2
Cough	1/21 (4.8%)	1	0/16 (0%)	0
Dyspnea	4/21 (19%)	4	2/16 (12.5%)	2
Laryngeal pain	1/21 (4.8%)	1	0/16 (0%)	0
Respiratory disorder	1/21 (4.8%)	1	1/16 (6.3%)	1
Skin and subcutaneous tissue disorders
Alopecia	3/21 (14.3%)	4	0/16 (0%)	0
Dry skin	1/21 (4.8%)	3	0/16 (0%)	0
Pain of skin	1/21 (4.8%)	1	0/16 (0%)	0
Pruritus	2/21 (9.5%)	3	2/16 (12.5%)	2
Rash desquamating	3/21 (14.3%)	5	3/16 (18.8%)	8
Skin disorder	1/21 (4.8%)	2	2/16 (12.5%)	2
Skin ulceration	1/21 (4.8%)	1	0/16 (0%)	0
Sweating	0/21 (0%)	0	1/16 (6.3%)	1
Vascular disorders
Flushing	1/21 (4.8%)	1	0/16 (0%)	0
Hemorrhage	1/21 (4.8%)	1	0/16 (0%)	0
Hypertension	1/21 (4.8%)	1	0/16 (0%)	0
Hypotension	2/21 (9.5%)	2	1/16 (6.3%)	1
Thrombosis	1/21 (4.8%)	1	0/16 (0%)	0

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.