Paclitaxel With or Without Viral Therapy in Treating Patients With Recurrent or Persistent Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cancer

Recurrent Ovarian Carcinoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01199263
• Other study ID #: NCI-2011-02654
• Secondary ID: NCI-2011-02654CD
• Status: Completed
• Phase: Phase 2
• Start date: December 6, 2010
• Est. completion date: July 17, 2020

Study information

• Verified date: August 2020
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 108
• Est. completion date: July 17, 2020
• Est. primary completion date: June 1, 2015
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Recurrent Fallopian Tube Carcinoma
• Recurrent Ovarian Carcinoma
• Recurrent Primary Peritoneal Carcinoma

Intervention

Other:
• Laboratory Biomarker Analysis
Correlative studies

Drug:
• Paclitaxel
Given IV

Biological:
• Pelareorep
Given IV

Locations

Country	Name	City	State
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Michigan Cancer Research Consortium NCORP	Ann Arbor	Michigan
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California
United States	Case Western Reserve University	Cleveland	Ohio
United States	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Atrium Health Cabarrus/LCI-Concord	Concord	North Carolina
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Beaumont Hospital - Dearborn	Dearborn	Michigan
United States	Ascension Saint John Hospital	Detroit	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Northeast Georgia Medical Center-Gainesville	Gainesville	Georgia
United States	Genesys Regional Medical Center	Grand Blanc	Michigan
United States	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut
United States	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	Allegiance Health	Jackson	Michigan
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Sparrow Hospital	Lansing	Michigan
United States	Women's Cancer Center of Nevada	Las Vegas	Nevada
United States	Saint Mary Mercy Hospital	Livonia	Michigan
United States	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio
United States	UH Seidman Cancer Center at Lake Health Mentor Campus	Mentor	Ohio
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Palo Alto Medical Foundation-Gynecologic Oncology	Mountain View	California
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Saint Joseph Mercy Oakland	Pontiac	Michigan
United States	Lake Huron Medical Center	Port Huron	Michigan
United States	Women and Infants Hospital	Providence	Rhode Island
United States	Carilion Clinic Gynecological Oncology	Roanoke	Virginia
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	Ascension Saint Mary's Hospital	Saginaw	Michigan
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)	NRG Oncology

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival (PFS)	Time from patient entry until progression, death, or date last seen. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), 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	Approximately 4.5 years.
Primary	Number of Participants With Adverse Events Grade 3 or Greater as Assessed by CTCAE Version 4.0	The frequency and severity of Grade 3 and above toxicities are tabulated.	approximately 4.5 years
Secondary	Percentage of Participants withTumor Response by RECIST	Participants with Complete and Partial Tumor Response by RECIST. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR	approximately 4.5 years
Secondary	Median Overall Survival (OS) by Treatment Group	Time from patient randomization to death or date last seen.	After patient stops protocol therapy, she is followed quarterly for 2 years, semi-annually for 3 more years, approximately 4.5 years.
Secondary	Tumor Response by CA125	Percentage of participants with Complete and Partial Tumor Response by CA125.	Before every cycle, approximately 4.5 years.