Brief Title
Viral Therapy in Treating Patients With Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer That Did Not Respond to Platinum Chemotherapy
Official Title
A Phase 1 Study of Reovirus Serotype 3 - Dearing Strain (REOLYSIN®) (NSC 729968) in Patients With Ovarian, Primary Peritoneal and Fallopian Tube Carcinoma
Brief Summary
This phase I/II trial is studying the side effects and best dose of viral therapy in treating
patients with ovarian epithelial cancer, primary peritoneal cancer, or fallopian tube cancer
that did not respond to platinum chemotherapy (phase II closed as of 1/7/2011). Viral therapy
may be able to kill tumor cells without damaging normal cells.
Detailed Description
PRIMARY OBJECTIVES:
I. Determine the safety and tolerability of intravenous (IV) and intraperitoneal (IP)
administration of wild-type reovirus (REOLYSIN®).
II. Determine the maximum tolerated dose of IP REOLYSIN® when used with a fixed dose of IV
REOLYSIN®.
III. Determine the objective response rate (complete response and partial response per
Response Evaluation Criteria in Solid Tumors [RECIST] criteria) of treatment with IV and IP
REOLYSIN® in patients with recurrent, platinum-refractory ovarian epithelial, peritoneal, or
fallopian tube carcinoma. (Phase II) (phase II closed as of 1/7/2011).
SECONDARY OBJECTIVES:
I. To identify viral replication in tumor following IV reovirus. II. To identify
anti-reovirus antibodies in patients being treated with IV and IP REOLYSIN® therapy.
III. To identify viral replication in the abdominal washings of patients undergoing IV and IP
REOLYSIN® therapy.
IV. To correlate response to therapy with Ras oncogene status. V. To evaluate double-stranded
RNA-activated protein kinase activity in tumors. VI. To correlate molecular predictors of
response to REOLYSIN® therapy.
OUTLINE: This is a phase I, dose-escalation study of intraperitoneal (IP) wild-type reovirus
when administered with fixed dose IV wild-type reovirus.
PHASE I: Patients receive wild-type reovirus IV over 60 minutes on days 1-5 in course 1,
followed by insertion of an IP access port. Beginning in course 2, patients receive wild-type
reovirus IV over 60 minutes on days 1-5 and wild-type reovirus IP over 10 minutes on days 1
and 2*. Treatment with IV and IP wild-type reovirus repeats every 28 days in the absence of
disease progression or unacceptable toxicity.
PHASE II: Patients undergo IP access port insertion before beginning treatment. Patients
receive wild-type reovirus IV over 60 minutes on days 1-5 and IP (at the maximum tolerated
dose determined in phase I) over 10 minutes on days 1 and 2*. Treatment repeats every 28 days
in the absence of disease progression or unacceptable toxicity (phase II closed as of
1/7/2011). NOTE: *Patients receive IP wild-type reovirus on days 2 and 3 in course 3.
Prior to each IP wild-type reovirus administration, normal saline is administered through the
IP catheter and withdrawn for correlative studies in courses 2 and 3 (phase I) or courses 1
and 2 (phase II). Patients also undergo a CT-guided percutaneous tumor biopsy on day 2 of
course 3 (phase I or II). Samples are analyzed by immunohistochemistry, RT-PCR, and electron
microscopy for the relevant molecular effects of wild-type reovirus on tumor and normal
tissue.
After completion of study treatment, patients are followed for up to 12 weeks.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Maximum tolerable dose of intraperitoneal (IP) wild-type reovirus when administered with fixed dose IV wild-type reovirus (phase I)
Secondary Outcome
Association of Ras oncogene and molecular markers with objective response
Condition
Recurrent Fallopian Tube Carcinoma
Intervention
Laboratory Biomarker Analysis
Study Arms / Comparison Groups
Treatment (viral therapy)
Description: Patients receive wild-type reovirus IV over 60 minutes on days 1-5 in course 1, followed by insertion of an IP access port. Beginning in course 2, patients receive wild-type reovirus IV over 60 minutes on days 1-5 and wild-type reovirus IP over 10 minutes on days 1 and 2*. Treatment with IV and IP wild-type reovirus repeats every 28 days in the absence of disease progression or unacceptable toxicity. (phase II closed as of 1/7/2011). NOTE: *Patients receive IP wild-type reovirus on days 2 and 3 in course 3.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Other
Estimated Enrollment
70
Start Date
April 2008
Completion Date
August 2016
Primary Completion Date
August 2016
Eligibility Criteria
Inclusion Criteria:
- Histologically confirmed ovarian epithelial, primary peritoneal, or fallopian tube
cancer
- Recurrent disease after platinum-based chemotherapy
- Must have experienced disease persistence during primary platinum-based therapy
or recurrence within 12 months after completion of platinum-based chemotherapy
("platinum-refractory" or "platinum-resistant" disease)
- A patient receiving a second course of platinum-based chemotherapy for
platinum-sensitive disease who then develops persistence or recurrence
within 12 months is considered eligible for this trial
- Must have measurable disease by RECIST criteria (phase II) (phase II closed as of
1/7/2011)
- Must have received ≥ 1 prior platinum-based cytotoxic chemotherapy regimen (for
primary disease) containing carboplatin, cisplatin, or other organoplatinum compound
- Initial treatment may have included any of the following:
- High-dose therapy
- Consolidation therapy
- Intraperitoneal (IP) therapy
- Extended therapy administered after surgical or nonsurgical assessment
- One additional non-cytotoxic regimen (e.g., monoclonal antibodies, cytokines, or
small-molecule inhibitors) for recurrent or persistent disease allowed
- Patients may have received hormonal therapy for management of disease (e.g., SERMs,
aromatase inhibitors, progestins, and GnRH agonists)
- No loculated ascites for which IP distribution of virus is not expected to be feasible
- No known brain metastases
- GOG performance status (PS) 0-2 (Karnofsky PS 60-100%)
- Life expectancy > 12 weeks
- Leukocytes ≥ 3,000/mcL
- Absolute neutrophil count ≥ 1,500/mcL
- Hemoglobin ≥ 10 g/dL
- Platelets ≥ 100,000/mcL
- Total bilirubin normal
- AST/ALT ≤ 2.5 times upper limit of normal
- Creatinine normal
- Ejection fraction > 50% by echocardiogram or MUGA
- Cardiac enzymes normal
- Not pregnant or nursing
- Fertile patients must use adequate contraception (hormonal or barrier method of birth
control or abstinence) prior to study entry and for the duration of study
participation
- Must be able to avoid direct contact with pregnant or nursing women, infants, or
immunocompromised individuals while on study and for ≥ 3 weeks following the last dose
of study agent administration
- Cardiac conduction abnormalities (e.g., bundle branch block, heart block) are allowed
if their cardiac status has been stable for 6 months before study entry
- At least 4 weeks since most recent cytotoxic chemotherapy (6 weeks for nitrosoureas or
mitomycin C)
- Recovered from adverse events due to agents administered more than 4 weeks earlier
- No prior radiotherapy to the abdomen or pelvis
- No other concurrent investigational agents
- No investigational or commercial agents or therapies other than those described below
may be administered with the intent to treat the patient's malignancy
Exclusion Criteria:
- Patients in whom insertion of an IP catheter is not feasible due to surgical
contraindications or abdominal and pelvic adhesions
- Known HIV infection or hepatitis B or C
- Clinically significant cardiac disease (New York Heart Association class III or IV
cardiac disease) including any of the following:
- Pre-existing arrhythmia
- Uncontrolled angina pectoris
- Myocardial infarction 1 year prior to study entry
- Compromised left ventricular ejection fraction ≥ grade 2 by MUGA or
echocardiogram
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, or psychiatric illness/social situations that would limit compliance with
study requirements
- Chronic oral steroids at an equivalent dose of prednisone 5 mg daily
- Inhaled steroids allowed
- Patients on immunosuppressive therapy
- Concurrent routine prophylactic use of growth factor (filgrastim [G-CSF] or
sargramostim [GM-CSF])
Gender
Female
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
David Cohn, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00602277
Organization ID
NCI-2009-00234
Secondary IDs
NCI-2009-00234
Responsible Party
Sponsor
Study Sponsor
National Cancer Institute (NCI)
Study Sponsor
David Cohn, Principal Investigator, Ohio State University Comprehensive Cancer Center
Verification Date
August 2016