Clinical trial NCT01199263: Paclitaxel With or Without Viral Therapy in Treating Patients With Recurrent or Persistent Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cancer
Official title: A Randomized Phase II Evaluation of Weekly Paclitaxel (NSC# 673089) Versus Weekly Paclitaxel With Oncolytic Reovirus (Reolysin NSC # 729968) in the Treatment of Recurrent or Persistent Ovarian, Fallopian Tube or Primary Peritoneal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Recurrent Fallopian Tube Carcinoma
Recurrent Ovarian Carcinoma
Recurrent Primary Peritoneal Carcinoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: NRG Oncology
First posted: 2010-09-10
Enrollment: 108
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This randomized phase II trial studies the side effects and how well giving paclitaxel with or without viral therapy works in treating patients with ovarian epithelial, fallopian tube, or primary peritoneal cancer that has come back. Drugs used in chemotherapy, such as 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 spreading. Viral therapy may be able to kill tumor cells without damaging normal cells. Giving paclitaxel together with viral therapy may kill more tumor cells.

Detailed description: PRIMARY OBJECTIVES:

I. To estimate the progression-free survival hazard ratio of the combination of weekly paclitaxel with Reolysin (wild-type reovirus) to weekly paclitaxel alone in patients with persistent or recurrent ovarian, fallopian tube, or primary peritoneal cancer.

II. To determine the frequency and severity of adverse events associated with treatment with weekly paclitaxel alone and weekly paclitaxel with REOLYSIN as assessed by Common Terminology Criteria for Adverse Events (CTCAE).

SECONDARY OBJECTIVES:

I. To estimate the progression-free survival and overall survival of patients treated with weekly paclitaxel alone and weekly paclitaxel with REOLYSIN.

II. To estimate (and compare) the proportion of patients who respond to the regimen on each arm of the study (according to Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1 with measurable patients and by cancer antigen \[CA\]-125 for those patients with detectable disease only).

III. To characterize and compare progression-free survival and overall survival in patients with measurable disease (RECIST 1.1 criteria) and patients with detectable (non-measurable) disease.

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

ARM I: Patients receive paclitaxel intravenously (IV) over 1 hour on days 1, 8, and 15.

ARM II: Patients receive paclitaxel as in arm I and wild-type reovirus IV over 1 hour on days 1-5.

In both arms, treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Eligibility criteria: Inclusion Criteria:

* Patients must have recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal carcinoma; histologic documentation of the original primary tumor is required via the pathology report
* Patients must have measurable disease or detectable (non-measurable) disease:

  * Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be \>= 10 mm when measured by computed tomography \[CT\], magnetic resonance imaging \[MRI\] or caliper measurement by clinical exam; or \>= 20 mm when measured by chest x-ray; lymph nodes must be \> 15 mm in short axis when measured by CT or MRI
  * Detectable (non-measurable) disease is defined as not having measurable disease but has at least one of the following conditions:

    * Baseline values of CA-125 at least 2 x upper limit of normal (ULN);
    * Ascites and/or pleural effusion attributed to tumor;
    * Solid and/or cystic abnormalities on radiographic imaging that do not meet RECIST 1.1 definitions for target lesions
* Patient with measurable disease must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST 1.1; tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy
* Patients must not be eligible for a higher priority Gynecologic Oncology Group (GOG) protocol, if one exists; in general, this would refer to any active GOG phase III protocol or rare tumor protocol for the same patient population
* Patients who have received one prior regimen must have a GOG performance status of 0, 1, or 2

  * Patients who have received two or three prior regimens must have a GOG performance status of 0 or 1
* Recovery from effects of recent surgery, radiotherapy, or chemotherapy:

  * Patients should be free of active infection requiring antibiotics (with the exception of uncomplicated urinary tract infection \[UTI\])
  * Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration; continuation of hormone replacement therapy is permitted
  * Any other prior therapy directed at the malignant tumor, including chemotherapy, biologic/targeted and immunologic agents, must be discontinued at least three weeks prior to registration
* Patients must have had one prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organoplatinum compound; this initial treatment may have included intraperitoneal therapy, consolidation, non-cytotoxic agents (biologic/targeted) or extended therapy administered after surgical or non-surgical assessment; if patients were treated with paclitaxel for their primary disease, this can have been given weekly or every 3 weeks
* Patients are allowed to receive, but are not required to receive, two additional cytotoxic regimens for management of recurrent or persistent disease, with no more than 1 non-platinum, non-taxane regimen; treatment with weekly paclitaxel for recurrent or persistent disease is NOT allowed
* Patients are allowed to receive, but are not required to receive, non-cytotoxic (biologic/targeted) therapy as part of their primary treatment regimen; patients are allowed to receive, but are not required to receive, non-cytotoxic (biologic/targeted) therapy as part of their treatment for recurrent or persistent disease and/or as treatment for recurrent or persistent disease; if non-cytotoxic (biologic/targeted) therapy is given alone (i.e., not in combination with cytotoxic chemotherapy) it will NOT count as a prior regimen

  * For the purposes of this study, poly (adenosine diphosphate \[ADP\]-ribose) polymerase (PARP) inhibitors will NOT count as a prior regimen when given alone (i.e., not in combination with cytotoxic chemotherapy)
* Patients who have received only one prior cytotoxic regimen (platinum-based regimen for management of primary disease), must have a platinum-free interval of less than 12 months, or have progressed during platinum-based therapy, or have persistent disease after a platinum-based therapy
* Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl
* Platelets greater than or equal to 100,000/mcl
* Hemoglobin greater than or equal to 9 g/dL
* Creatinine less than or equal to 1.5 x institutional upper limit normal (ULN)
* Bilirubin less than or equal to 1.5 x ULN
* Serum glutamic oxaloacetic transaminase (SGOT) less than or equal to 3 x ULN
* Alkaline phosphatase less than or equal to 2.5 x ULN
* Neuropathy (sensory and motor) less than or equal to grade 1
* Patients of childbearing potential must have a negative pregnancy test prior to the study entry and be practicing an effective form of contraception; (pregnant women are excluded from this study)
* Patients must have signed an approved informed consent and authorization permitting the release of personal health information
* Patients must meet pre-entry requirements as specified
* Patients must be able to avoid direct contact with severely immune-compromised individuals such as patients who have had a recent bone-marrow or organ transplant or patients with acquire immunodeficiency syndrome (AIDS); contact should be avoided on the days of Reolysin treatment and for the 2 days following Reolysin treatment
* Patients must be able to avoid direct contact with pregnant or nursing women and infants while receiving Reolysin; contact should be avoided on the days of Reolysin treatment and for the 2 days following Reolysin treatment

Exclusion Criteria:

* Patient who have had previous treatment with Reolysin or other oncolytic virus; patients who have had previous treatment with weekly paclitaxel for recurrent or persistent disease
* Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer and other specific malignancies are excluded if there is any evidence of other malignancy being present within the last three years; patients are also excluded if their previous cancer treatment contraindicates this protocol therapy
* Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis OTHER THAN for the treatment of ovarian, fallopian tube, or primary peritoneal cancer within the last three years are excluded; prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease
* Patients who have received prior chemotherapy for any abdominal or pelvic tumor OTHER THAN for the treatment of ovarian, fallopian tube, or primary peritoneal cancer within the last three years are excluded; patients may have received prior adjuvant chemotherapy for localized breast cancer, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease
* Patients with a past history of primary endometrial cancer are excluded unless all of the following conditions are met: stage not greater than I-B; no more than superficial myometrial invasion, without vascular or lymphatic invasion; no poorly differentiated subtypes, including papillary serious, clear cell or other International Federation of Gynecology and Obstetrics (FIGO) grade 3 lesions
* Patients with known human immunodeficiency virus (HIV) or hepatitis B or C are excluded due to risk of viral infectivity of Reolysin therefore patients with a pre-existent infection are not eligible
* Patients who are receiving immunosuppressive therapy including chronic oral steroids (at an equivalent dose of greater than prednisone 5 mg daily)
* Women who are pregnant or nursing; pregnant women are excluded from this study; breastfeeding should be discontinued while the mother is being treated with the agents in this clinical trial
* Myocardial infarction or unstable angina within 6 months of the first date of study therapy
* History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation) or cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well controlled with antiarrhythmic medication)
* Troponin \> ULN
* Baseline ejection fraction \< 50% as assessed by echocardiogram or multi gated acquisition scan (MUGA)
* New York Heart Association (NYHA) class II or greater congestive heart failure
* History of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months of the first date of study therapy

Primary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: Approximately 4.5 years.
measure: Number of Participants With Adverse Events Grade 3 or Greater as Assessed by CTCAE Version 4.0
timeFrame: approximately 4.5 years
Secondary outcomes:
measure: Percentage of Participants withTumor Response by RECIST
timeFrame: approximately 4.5 years
measure: Median Overall Survival (OS) by Treatment Group
timeFrame: After patient stops protocol therapy, she is followed quarterly for 2 years, semi-annually for 3 more years, approximately 4.5 years.
measure: Tumor Response by CA125
timeFrame: Before every cycle, approximately 4.5 years.
Other outcomes:
Locations:
city: Burbank
country: United States
facility: Providence Saint Joseph Medical Center/Disney Family Cancer Center
state: California
city: Mountain View
country: United States
facility: Palo Alto Medical Foundation-Gynecologic Oncology
state: California
city: Hartford
country: United States
facility: Smilow Cancer Hospital Care Center at Saint Francis
state: Connecticut
city: Gainesville
country: United States
facility: Northeast Georgia Medical Center-Gainesville
state: Georgia
city: Boise
country: United States
facility: Saint Alphonsus Cancer Care Center-Boise
state: Idaho
city: Indianapolis
country: United States
facility: Indiana University/Melvin and Bren Simon Cancer Center
state: Indiana
city: Ann Arbor
country: United States
facility: Michigan Cancer Research Consortium NCORP
state: Michigan
city: Ann Arbor
country: United States
facility: Saint Joseph Mercy Hospital
state: Michigan
city: Dearborn
country: United States
facility: Beaumont Hospital - Dearborn
state: Michigan
city: Detroit
country: United States
facility: Ascension Saint John Hospital
state: Michigan
city: Flint
country: United States
facility: Hurley Medical Center
state: Michigan
city: Grand Blanc
country: United States
facility: Genesys Regional Medical Center
state: Michigan
city: Jackson
country: United States
facility: Allegiance Health
state: Michigan
city: Lansing
country: United States
facility: Sparrow Hospital
state: Michigan
city: Livonia
country: United States
facility: Saint Mary Mercy Hospital
state: Michigan
city: Pontiac
country: United States
facility: Saint Joseph Mercy Oakland
state: Michigan
city: Port Huron
country: United States
facility: Lake Huron Medical Center
state: Michigan
city: Saginaw
country: United States
facility: Ascension Saint Mary's Hospital
state: Michigan
city: Warren
country: United States
facility: Saint John Macomb-Oakland Hospital
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Las Vegas
country: United States
facility: Women's Cancer Center of Nevada
state: Nevada
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Center
state: New Mexico
city: Concord
country: United States
facility: Atrium Health Cabarrus/LCI-Concord
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Cancer Center/Fairview Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
city: Mayfield Heights
country: United States
facility: Hillcrest Hospital Cancer Center
state: Ohio
city: Mentor
country: United States
facility: UH Seidman Cancer Center at Lake Health Mentor Campus
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Providence
country: United States
facility: Women and Infants Hospital
state: Rhode Island
city: Dallas
country: United States
facility: UT Southwestern/Simmons Cancer Center-Dallas
state: Texas
city: Roanoke
country: United States
facility: Carilion Clinic Gynecological Oncology
state: Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: NRG Oncology
name: David E Cohn
role: PRINCIPAL_INVESTIGATOR
References: