Carboplatin and Paclitaxel With or Without Viral Therapy in Treating Patients With Recurrent or Metastatic Pancreatic Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT01280058
• Collaborator: (none)
• Enrollment: 73
• Locations: 6
• Arms: 2
• Actual Duration (Months): 61.6
• Patients Per Site: 12.2
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This phase II trial studies how well carboplatin and paclitaxel with or without viral therapy works in treating patients with pancreatic cancer that has come back or has spread to other places in the body. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Viral therapy may be able to kill tumor cells without damaging normal cells. It is not yet known whether carboplatin and paclitaxel are more effective with or without viral therapy in treating pancreatic cancer.

Condition or Disease	Intervention/Treatment	Phase
Pancreatic Acinar Cell Carcinoma; Pancreatic Ductal Adenocarcinoma; Recurrent Pancreatic Carcinoma; Stage IV Pancreatic Cancer	Drug: Carboplatin; Other: Laboratory Biomarker Analysis; Drug: Paclitaxel; Biological: Wild-type Reovirus	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To assess the improvement in progression-free survival with Reolysin (wild-type reovirus), carboplatin, and paclitaxel relative to carboplatin and paclitaxel alone in patients with recurrent or metastatic pancreatic cancer.

SECONDARY OBJECTIVES:

1. To evaluate the safety and tolerability of Reolysin in combination with carboplatin and paclitaxel versus without Reolysin in patients with recurrent or metastatic pancreas cancer.

2. To compare the treatment groups for other efficacy endpoints such as overall response rate and overall survival.

3. To define how the combination of Reolysin and carboplatin and paclitaxel (CP) modulate factors regulating immunity to reovirus and its persistence in the system circulation of patients with pancreatic cancer.

4. To prospectively establish and validate the relationship between Ras mutations in tumor samples and response to Reolysin.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive paclitaxel intravenously (IV) over 3 hours and carboplatin IV over 30 minutes on day 1 and wild-type reovirus IV over 60 minutes on days 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive paclitaxel and carboplatin as in Arm I. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may crossover to Arm I.

After completion of study treatment, patients are followed up at 1 month and then every 2 months thereafter.

Study Design

• Study Type: Interventional
• Actual Enrollment: 73 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A 2-arm Randomized Phase II Study of Carboplatin, Paclitaxel Plus Reovirus Serotype-3 Dearing Strain (Reolysin) vs. Carboplatin and Paclitaxel in the First Line Treatment of Patients With Recurrent or Metastatic Pancreatic Cancer
• Actual Study Start Date: Dec 1, 2010
• Actual Primary Completion Date: Jan 19, 2016
• Actual Study Completion Date: Jan 20, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I (wild-type reovirus, carboplatin, paclitaxel) Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 and wild-type reovirus IV over 60 minutes on days 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Drug: Carboplatin; Given IV; Other Names: Blastocarb Carboplat Carboplatin Hexal Carboplatino Carbosin Carbosol Carbotec CBDCA Displata Ercar JM-8 Nealorin Novoplatinum Paraplat Paraplatin Paraplatin AQ Paraplatine Platinwas Ribocarbo ; Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Paclitaxel; Given IV; Other Names: Anzatax Asotax Bristaxol Praxel Taxol Taxol Konzentrat ; Biological: Wild-type Reovirus; Given IV; Other Names: Reolysin
Experimental: Arm II (carboplatin, paclitaxel) Patients receive paclitaxel and carboplatin as in Arm I. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may crossover to Arm I.	Drug: Carboplatin; Given IV; Other Names: Blastocarb Carboplat Carboplatin Hexal Carboplatino Carbosin Carbosol Carbotec CBDCA Displata Ercar JM-8 Nealorin Novoplatinum Paraplat Paraplatin Paraplatin AQ Paraplatine Platinwas Ribocarbo ; Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Paclitaxel; Given IV; Other Names: Anzatax Asotax Bristaxol Praxel Taxol Taxol Konzentrat

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival Using RECIST v. 1.1 [From study entry to the date of documented progression and/or death, assessed up to 4 years]

   The progression-free survival distributions between the two arms will be compared using log-rank tests. Progression-free survival curves will be constructed using the Kaplan-Meier product limit method, and additional analyses will be done using the Cox proportional hazards model.

Secondary Outcome Measures

1. Incidence of Severe (Grade 3+) Adverse Events That Are Classified as Either Possibly, Probably, or Definitely Related to Study Treatment, as Assessed by NCI CTCAE Version 4.0 [Up to 4 years]

   Toxicities will be described for each treatment arm, but will also be compared between the arms. Fisher's exact tests will be used to quantitatively compare the incidence of severe as well as specific toxicities of interest between the treatment arms and we will graphically assess differences in maximum grades observed for toxicities between the arms.

2. Overall Response Rate (Partial or Complete Response) Evaluated Using the Standard RECIST v. 1.1 [Up to 4 years]

   95% confidence intervals will be calculated. Differences in objective response rates between the treatment arms will be assessed using Fisher's exact test.

3. Overall Survival [From study entry to the time of death due to any cause, assessed up to 4 years]

   Evaluated and compared between the two treatment groups using log-rank statistics and graphically using the methods of Kaplan and Meier.

Other Outcome Measures

1. Immunologic Correlative Markers [Up to day 1 of course 12]

   The inflammatory cytokine profile, immune effector cell phenotype and function, and NARA titers will be assessed and compared. Patterns of change in the longitudinal data on these markers will be evaluated for each of the correlative outcomes of interest.

2. Percentage of Patients With Ras Pathway Activation [Baseline]

   The 95% confidence interval will be assessed. Cochran-Mantel-Haenszel test will be used to assess differences in the relationships between response and Ras pathway activation and the association of treatment groups on these relationships.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically confirmed adenocarcinoma of the pancreas that is recurrent or metastatic; cytological confirmation is not allowed on this study; paraffin embedded tissue from tumor blocks will be required from patients before enrolling on this study; diagnosis of pancreas cancer with histologic confirmation of adenocarcinoma would suffice

• Patients must have measurable disease, defined as one lesion that can be accurately measured in at least one dimension per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (longest diameter to be recorded) as >= 10 mm by spiral computed tomography (CT) scan (CT scan slice thickness no greater than 5 mm); malignant lymph nodes will be considered measurable if they are >= 15 mm in short axis; for patients previously irradiated, the measurable lesion must be outside the radiated field

• Patients must not have received any prior chemotherapy in metastatic setting; patients who have received prior chemotherapy in the adjuvant setting will not be eligible for our study; patients should not have received prior Reolysin; prior palliative radiation therapy or major surgery must have occurred at least 28 days prior to study enrollment; prior minor surgeries (such as laparoscopies) must have occurred at least 14 days prior to study enrollment; prior minor procedures such as biopsies and mediport placement must have occurred at least 48 hours prior to study enrollment

• Eastern Cooperative Oncology Group (ECOG) status =< 1 (Karnofsky >= 70%)

• Absolute neutrophil count (ANC) >= 1.5 x 10^9/L International System of Units (SI) units

• Platelet count >= 100 x10^9/L SI units

• Hemoglobin >= 8.5 g/dL SI units

• Serum creatinine =< 1.5 mg/dL OR creatinine clearance >= 60 mL/min

• Bilirubin =< upper limit of normal (ULN) (=< 2 x ULN if it is non-rising for a period of 10 days prior to initiation of therapy)

• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 X ULN

• Troponin I < ULN

• All patients must have signed an informed consent indicating that they are aware of the neoplastic nature of their disease and have been informed of the procedures of the protocol, the experimental nature of the therapy, alternatives, potential benefits, side effects, risks, and discomforts

• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; patients must be able to avoid direct contact with pregnant or nursing women, infants and immunocompromised individuals while on study and for >= 3 weeks following the last dose of Reolysin administration

• All patients must be willing and able to comply with scheduled visits, the treatment plan, and laboratory tests

Exclusion Criteria:

• Patients may not be receiving any other investigational agents or concurrent therapy with other anti-cancer agents while on study

• Patients with untreated brain metastases will be excluded from this clinical trial; however, patients with resected oligometastasis are eligible if postresection magnetic resonance imaging (MRI) demonstrates resolution; gamma-knife treated patients are also eligible if there are no more than two treated metastases confined to the same area of the brain and a post treatment MRI shows a decrease in the metastases

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to Reolysin or other agents used in the study

• Patients may not have received any viral-based therapy within the past 6 months

• Patients must have NO continuing acute toxic effects (except alopecia) of any prior radiotherapy, chemotherapy, or surgical procedures; all such effects must have resolved to Common Terminology Criteria for Adverse Events (CTCAE, version [v.] 4 ) grade =< 1 prior to study enrollment

• Patients must not have grade 2 or higher baseline peripheral neuropathy according to CTCAE v. 4

• Patients with uncontrolled cardiac dysfunction or arrhythmia, including a myocardial infarction in the preceding 6 months, known cardiac ejection fraction < 40%, symptomatic congestive heart failure, or unstable angina pectoris

• Patients must not be receiving concurrent systemic immunosuppressive therapy

• Patients must not have known human immunodeficiency virus (HIV) infection or active hepatitis B or C

• Patients must not have uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or known psychiatric illness/social situations that would limit compliance with study requirements

• Patients must not have dementia or altered mental status that would prohibit informed consent

• Patients must not have other known severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation, study drug administration, or may interfere with the interpretation of study results that, in the judgment of the Principal Investigator, would make the patient inappropriate for this study

• Pregnant women are excluded from this study; breastfeeding should be discontinued while the mother is being treated with the agents in this clinical trial

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	MedStar Georgetown University Hospital	Washington	District of Columbia	United States	20007
2	Emory University/Winship Cancer Institute	Atlanta	Georgia	United States	30322
3	Montefiore Medical Center-Weiler Hospital	Bronx	New York	United States	10461
4	Montefiore Medical Center - Moses Campus	Bronx	New York	United States	10467-2490
5	Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210
6	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Anne Noonan, Ohio State University Comprehensive Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT01280058
• Other Study ID Numbers: NCI-2011-02567; NCI-2011-02567; OSU 10045; OSU-10045; CDR0000692060; 8601; 8601; N01CM00070; N01CM62207; P30CA016058
• First Posted: Jan 20, 2011
• Last Update Posted: Mar 9, 2018
• Last Verified: Feb 1, 2018

• Additional relevant MeSH terms: Carcinoma; Pancreatic Neoplasms; Carcinoma, Acinar Cell; Recurrence; Paclitaxel; Carboplatin; Albumin-Bound Paclitaxel

Study Results

Participant Flow

Recruitment Details	Patients were randomized between February 2011 and April 2014

Arm/Group Title	Arm A (Wild-type Reovirus, Carboplatin, Paclitaxel)	Arm B (Carboplatin, Paclitaxel)
Arm/Group Description	Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 and wild-type reovirus IV over 60 minutes on days 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Paclitaxel: Given IV Wild-type Reovirus: Given IV	Patients receive paclitaxel and carboplatin as in Arm I. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may crossover to Arm I. Carboplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Paclitaxel: Given IV
Period Title: Overall Study
STARTED	36	37
COMPLETED	36	37
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Arm A (Wild-type Reovirus, Carboplatin, Paclitaxel)	Arm B (Carboplatin, Paclitaxel)	Total
Arm/Group Description	Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 and wild-type reovirus IV over 60 minutes on days 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Paclitaxel: Given IV Wild-type Reovirus: Given IV	Patients receive paclitaxel and carboplatin as in Arm I. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may crossover to Arm I. Carboplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Paclitaxel: Given IV	Total of all reporting groups
Overall Participants	36	37	73
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	61.5	66	64
Sex: Female, Male (Count of Participants)
Female	14 38.9%	18 48.6%	32 43.8%
Male	22 61.1%	19 51.4%	41 56.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 2.8%	0 0%	1 1.4%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 5.6%	0 0%	2 2.7%
White	32 88.9%	35 94.6%	67 91.8%
More than one race	0 0%	1 2.7%	1 1.4%
Unknown or Not Reported	1 2.8%	1 2.7%	2 2.7%
Region of Enrollment (Count of Participants)
United States	36 100%	37 100%	73 100%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival Using RECIST v. 1.1
Description	The progression-free survival distributions between the two arms will be compared using log-rank tests. Progression-free survival curves will be constructed using the Kaplan-Meier product limit method, and additional analyses will be done using the Cox proportional hazards model.
Time Frame	From study entry to the date of documented progression and/or death, assessed up to 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A (Wild-type Reovirus, Carboplatin, Paclitaxel)	Arm B (Carboplatin, Paclitaxel)
Arm/Group Description	Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 and wild-type reovirus IV over 60 minutes on days 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Paclitaxel: Given IV Wild-type Reovirus: Given IV	Patients receive paclitaxel and carboplatin as in Arm I. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may crossover to Arm I. Carboplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Paclitaxel: Given IV
Measure Participants	36	37
Median (95% Confidence Interval) [months]	4.9	5.2

2. Secondary Outcome

Title	Incidence of Severe (Grade 3+) Adverse Events That Are Classified as Either Possibly, Probably, or Definitely Related to Study Treatment, as Assessed by NCI CTCAE Version 4.0
Description	Toxicities will be described for each treatment arm, but will also be compared between the arms. Fisher's exact tests will be used to quantitatively compare the incidence of severe as well as specific toxicities of interest between the treatment arms and we will graphically assess differences in maximum grades observed for toxicities between the arms.
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A (Wild-type Reovirus, Carboplatin, Paclitaxel)	Arm B (Carboplatin, Paclitaxel)
Arm/Group Description	Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 and wild-type reovirus IV over 60 minutes on days 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Paclitaxel: Given IV Wild-type Reovirus: Given IV	Patients receive paclitaxel and carboplatin as in Arm I. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may crossover to Arm I. Carboplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Paclitaxel: Given IV
Measure Participants	36	37
Neutropenia	56	59
Leukopenia	33	46
Thrombocytopenia	28	24
Anemia	25	30
Febrile Neutropenia	8	11
Fatigue	11	8
Infection	11	5
Dose Delay	37	54
Dose reduction	36	43

3. Secondary Outcome

Title	Overall Response Rate (Partial or Complete Response) Evaluated Using the Standard RECIST v. 1.1
Description	95% confidence intervals will be calculated. Differences in objective response rates between the treatment arms will be assessed using Fisher's exact test.
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A (Wild-type Reovirus, Carboplatin, Paclitaxel)	Arm B (Carboplatin, Paclitaxel)
Arm/Group Description	Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 and wild-type reovirus IV over 60 minutes on days 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Paclitaxel: Given IV Wild-type Reovirus: Given IV	Patients receive paclitaxel and carboplatin as in Arm I. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may crossover to Arm I. Carboplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Paclitaxel: Given IV
Measure Participants	36	37
Partial Response	7 19.4%	7 18.9%
Complete Response	0 0%	0 0%

4. Secondary Outcome

Title	Overall Survival
Description	Evaluated and compared between the two treatment groups using log-rank statistics and graphically using the methods of Kaplan and Meier.
Time Frame	From study entry to the time of death due to any cause, assessed up to 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A (Wild-type Reovirus, Carboplatin, Paclitaxel)	Arm B (Carboplatin, Paclitaxel)
Arm/Group Description	Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 and wild-type reovirus IV over 60 minutes on days 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Paclitaxel: Given IV Wild-type Reovirus: Given IV	Patients receive paclitaxel and carboplatin as in Arm I. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may crossover to Arm I. Carboplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Paclitaxel: Given IV
Measure Participants	36	37
Median (95% Confidence Interval) [months]	7.3	8.8

5. Other Pre-specified Outcome

Title	Immunologic Correlative Markers
Description	The inflammatory cytokine profile, immune effector cell phenotype and function, and NARA titers will be assessed and compared. Patterns of change in the longitudinal data on these markers will be evaluated for each of the correlative outcomes of interest.
Time Frame	Up to day 1 of course 12

Outcome Measure Data

Analysis Population Description

data was not collected

Arm/Group Title	Arm I (Wild-type Reovirus, Carboplatin, Paclitaxel)	Arm II (Carboplatin, Paclitaxel)
Arm/Group Description	Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 and wild-type reovirus IV over 60 minutes on days 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Paclitaxel: Given IV Wild-type Reovirus: Given IV	Patients receive paclitaxel and carboplatin as in Arm I. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may crossover to Arm I. Carboplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Paclitaxel: Given IV
Measure Participants	0	0

6. Other Pre-specified Outcome

Title	Percentage of Patients With Ras Pathway Activation
Description	The 95% confidence interval will be assessed. Cochran-Mantel-Haenszel test will be used to assess differences in the relationships between response and Ras pathway activation and the association of treatment groups on these relationships.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A (Wild-type Reovirus, Carboplatin, Paclitaxel)	Arm B (Carboplatin, Paclitaxel)
Arm/Group Description	Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 and wild-type reovirus IV over 60 minutes on days 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Paclitaxel: Given IV Wild-type Reovirus: Given IV	Patients receive paclitaxel and carboplatin as in Arm I. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may crossover to Arm I. Carboplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Paclitaxel: Given IV
Measure Participants	36	37
Number [percentage of patients]	71	75

Adverse Events

Adverse Event Reporting Description	The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was used for adverse event grading and reporting.
Arm/Group Title	Arm A (Wild-type Reovirus, Carboplatin, Paclitaxel)		Arm B (Carboplatin, Paclitaxel)
Arm/Group Description	Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 and wild-type reovirus IV over 60 minutes on days 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Carboplatin and Paclitaxel were given IV. Wild-type Reovirus: Given IV		Patients receive paclitaxel and carboplatin as in Arm I. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may crossover to Arm I. Carboplatin and Paclitaxel were given IV
All Cause Mortality
	Arm A (Wild-type Reovirus, Carboplatin, Paclitaxel)		Arm B (Carboplatin, Paclitaxel)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm A (Wild-type Reovirus, Carboplatin, Paclitaxel)		Arm B (Carboplatin, Paclitaxel)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	36/36 (100%)		37/37 (100%)
Blood and lymphatic system disorders
Anemia	10/36 (27.8%)	10	11/37 (29.7%)	11
Febrile Neutropenia	4/36 (11.1%)	4	5/37 (13.5%)	5
Cardiac disorders
Atrial fibrillation	2/36 (5.6%)	2	0/37 (0%)	0
Cardiac arrest	1/36 (2.8%)	1	0/37 (0%)	0
Chest pain-cardiac	1/36 (2.8%)	1	0/37 (0%)	0
Sinus tachycardia	1/36 (2.8%)	1	0/37 (0%)	0
Gastrointestinal disorders
Abdominal distension	2/36 (5.6%)	2	2/37 (5.4%)	2
Abdominal pain	6/36 (16.7%)	6	5/37 (13.5%)	5
Ascites	3/36 (8.3%)	3	3/37 (8.1%)	3
Constipation	1/36 (2.8%)	1	0/37 (0%)	0
Diarrhea	2/36 (5.6%)	2	3/37 (8.1%)	3
Bloating	0/36 (0%)	0	1/37 (2.7%)	1
Gastric hemorrhage	1/36 (2.8%)	1	1/37 (2.7%)	1
Gastric ulcer	1/36 (2.8%)	1	0/37 (0%)	0
Lower gastrointestional hemorrhage	1/36 (2.8%)	1	0/37 (0%)	0
Nausea	7/36 (19.4%)	7	7/37 (18.9%)	7
Pancreatitis	1/36 (2.8%)	1	1/37 (2.7%)	1
Rectal hemorrhage	1/36 (2.8%)	1	0/37 (0%)	0
Vomiting	5/36 (13.9%)	5	4/37 (10.8%)	4
General disorders
Edema limbs	2/36 (5.6%)	2	1/37 (2.7%)	1
Fatigue	6/36 (16.7%)	6	2/37 (5.4%)	2
Fever	1/36 (2.8%)	1	1/37 (2.7%)	1
Infusion related reaction	1/36 (2.8%)	1	1/37 (2.7%)	1
Pain	2/36 (5.6%)	2	3/37 (8.1%)	3
Non-cardiac chest pain	0/36 (0%)	0	1/37 (2.7%)	1
Hepatobiliary disorders
Bile duct stenosis	3/36 (8.3%)	3	0/37 (0%)	0
Infections and infestations
Device related infection	1/36 (2.8%)	1	0/37 (0%)	0
Infections	2/36 (5.6%)	2	2/37 (5.4%)	2
Lung Infection	1/36 (2.8%)	1	0/37 (0%)	0
Sepsis	3/36 (8.3%)	3	1/37 (2.7%)	1
Skin Infection	2/36 (5.6%)	2	0/37 (0%)	0
Upper Respiratory Infection	1/36 (2.8%)	1	0/37 (0%)	0
Urinary Tract Infection	3/36 (8.3%)	3	1/37 (2.7%)	1
Injury, poisoning and procedural complications
Fracture	1/36 (2.8%)	1	1/37 (2.7%)	1
Injury, poisoning and procedural complications	1/36 (2.8%)	1	0/37 (0%)	0
Postoperative hemorrhage	1/36 (2.8%)	1	0/37 (0%)	0
Investigations
Alanine aminotransferase increased	3/36 (8.3%)	3	2/37 (5.4%)	2
Alkaline phosphatase increased	1/36 (2.8%)	1	1/37 (2.7%)	1
Aspartate aminotransferase increased	3/36 (8.3%)	3	2/37 (5.4%)	2
Blood bilirubin increased	7/36 (19.4%)	7	4/37 (10.8%)	4
Cardiac troponin I increaesd	3/36 (8.3%)	3	0/37 (0%)	0
Neutrophil count decreased	15/36 (41.7%)	15	13/37 (35.1%)	13
Platelet count decreased	10/36 (27.8%)	10	4/37 (10.8%)	4
White blood cell decreased	10/36 (27.8%)	10	8/37 (21.6%)	8
Metabolism and nutrition disorders
Dehydration	2/36 (5.6%)	2	1/37 (2.7%)	1
Hypokalemia	4/36 (11.1%)	4	1/37 (2.7%)	1
Hyperglycemia	0/36 (0%)	0	2/37 (5.4%)	2
Nervous system disorders
Dizziness	2/36 (5.6%)	2	2/37 (5.4%)	2
Peripheral sensory	2/36 (5.6%)	2	0/37 (0%)	0
Transient ischemic attacks	2/36 (5.6%)	2	0/37 (0%)	0
Psychiatric disorders
Confusion	4/36 (11.1%)	4	2/37 (5.4%)	2
Renal and urinary disorders
Acute kidney injury	4/36 (11.1%)	4	1/37 (2.7%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	5/36 (13.9%)	5	1/37 (2.7%)	1
Respiratory failure	2/36 (5.6%)	2	1/37 (2.7%)	1
Vascular disorders
Hypertension	2/36 (5.6%)	2	0/37 (0%)	0
Hypostension	1/36 (2.8%)	1	2/37 (5.4%)	2
Thromboembolic event	4/36 (11.1%)	4	3/37 (8.1%)	3
Other (Not Including Serious) Adverse Events
	Arm A (Wild-type Reovirus, Carboplatin, Paclitaxel)		Arm B (Carboplatin, Paclitaxel)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	36/36 (100%)		37/37 (100%)
Blood and lymphatic system disorders
Neutropenia	20/36 (55.6%)	20	22/37 (59.5%)	22
Leukopenia	12/36 (33.3%)	12	17/37 (45.9%)	17
Thrombocytopenia	10/36 (27.8%)	10	9/37 (24.3%)	9
Anemia	9/36 (25%)	9	11/37 (29.7%)	11
General disorders
Fatigue	4/36 (11.1%)	4	3/37 (8.1%)	3
Infections and infestations
Febrile Neutropenia	3/36 (8.3%)	3	4/37 (10.8%)	4
Infection	4/36 (11.1%)	4	2/37 (5.4%)	2

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.