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A Phase 1 Study of Reovirus Serotype 3 - Dearing Strain (REOLYSIN®) (NSC 729968) in Patients With Ovarian, Primary Peritoneal and Fallopian Tube Carcinoma


Phase 1
18 Years
N/A
Open (Enrolling)
Female
Recurrent Fallopian Tube Cancer, Recurrent Ovarian Epithelial Cancer, Recurrent Primary Peritoneal Cavity Cancer

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Trial Information

A Phase 1 Study of Reovirus Serotype 3 - Dearing Strain (REOLYSIN®) (NSC 729968) in Patients With Ovarian, Primary Peritoneal and Fallopian Tube Carcinoma


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.


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])

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerable dose of intraperitoneal (IP) wild-type reovirus when administered with fixed dose IV wild-type reovirus (phase I)

Outcome Description:

Dose-limiting toxicity will be assessed using the Common Terminology Criteria for Adverse Events (CTCAE) v. 4

Outcome Time Frame:

At each dose level, assessed up to 5 dose levels

Safety Issue:

Yes

Principal Investigator

David Cohn

Investigator Role:

Principal Investigator

Investigator Affiliation:

Ohio State University

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2009-00234

NCT ID:

NCT00602277

Start Date:

April 2008

Completion Date:

Related Keywords:

  • Recurrent Fallopian Tube Cancer
  • Recurrent Ovarian Epithelial Cancer
  • Recurrent Primary Peritoneal Cavity Cancer
  • Peritoneal Neoplasms
  • Fallopian Tube Neoplasms
  • Neoplasms, Glandular and Epithelial
  • Ovarian Neoplasms

Name

Location

Ohio State University Medical CenterColumbus, Ohio  43210