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Tivozanib 1.5mg orally given daily for 3 weeks with one week off to complete a 4 week cycle until disease progression or adverse effects prohibit further therapy

1.5 mg Given PO (orally)days 1-21 or every 28 day cycle

Daniela Matei, MD

This phase II trial studies how well tivozanib works in treating patients with recurrent ovarian, fallopian tube, or primary peritoneal cancer. Tivozanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. To determine the clinical activity of tivozanib in patients with platinum-resistant, recurrent ovarian, fallopian tube or primary peritoneal cancer.

SECONDARY OBJECTIVES:

I. Determining the potential survival advantage and characterizing the safety of single agent tivozanib in patients with platinum-resistant ovarian cancer.

OUTLINE:

Patients receive tivozanib hydrochloride orally (PO) once daily (QD) on days 1-21. Courses repeat every 4 weeks 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.

Tivozanib in Recurrent, Platinum-Resistant Ovarian, Fallopian Tube or Primary Peritoneal Cancer

The Efficacy and Safety of Tivozanib in Recurrent, Platinum-Resistant Ovarian, Fallopian Tube or Primary Peritoneal Cancer

ORR is defined as the number of patients with complete response plus those with partial response as measured by RECIST 1.1 where:

Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

The Kaplan-Meier method will be utilized to estimate the median and overall distribution of PFS and will be defined from the start of treatment until the first documentation of progressive disease or death, whichever occurs first..

Adverse events will be assessed by NCI CTCAE v 4.03. Adverse event that were determined to be serious adverse events (either grade 3, 4, or 5) related to study drug were collected. Grading is as follows:In general the following severity definitions are true:

Mild (grade 1): the event causes discomfort without disruption of normal daily activities.

Moderate (grade 2): the event causes discomfort that affects normal daily activities.

Severe (grade 3): the event makes the patient unable to perform normal daily activities or significantly affects his/her clinical status.

Life-threatening (grade 4): the patient was at risk of death at the time of the event. Fatal (grade 5): the event caused death.

OS is defined from the start of treatment until date of death from any cause or date of last contact.

National Comprehensive Cancer Network

Northwestern University

Tivozanib 1.5mg orally given daily for 3 weeks with one week off to complete a 4 week cycle until disease progression or adverse effects prohibit further therapy

Tivozanib: 1.5 mg Given PO (orally)days 1-21 or every 28 day cycle

Treatment (Tivozanib)

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Daniela Matei

6 patients who were determined to not be evaluable and are not included in the overall number of patients analyzed

Overall Response Rate (ORR)

Progression Free Survival (PFS) in Platinum-resistant Ovarian Cancer to Treatment With Single Agent Tivozanib

Hypertension

Fatigue

Hyponatremia

Colonic Fistula

Nausea

Hypomagnesemia

Anemia

Proteinuria

Hypoalbuminemia

Small intestinal perforation

Portal hypertension

Stroke

Small intestinal obstruction

Number of Patients Who Experienced Adverse Events in Platinum-resistant Ovarian Cancer to Treatment With Single Agent Tivozanib

Overall Survival (OS) in Platinum-resistant Ovarian Cancer to Treatment With Single Agent Tivozanib

Overall Best Response as measured by physical exam findings, serum CA125 levels and/or measurement of index lesions via appropriate imaging studies using RECIST criteria defined as either:

Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note:the appearance of one or more new lesions is also considered progressions).

Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

Overall Best Response of Patients With Platinum-resistant Ovarian Cancer to Treatment With Single Agent Tivozanib

CBR is defined as the number of patients with Complete Response (CR) plus those with Partial Response (PR) plus those with Stable Disease (SD) as assessed by RECIST 1.1 where:

Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note:the appearance of one or more new lesions is also considered progressions).

Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

6 patients were determined to be not evaluable are not included in the overall number of patients analyzed

Clinical Benefit Rate (CBR)

3 months

6 months

12 months

PFS rate will be measured by the number of patients that are progression free at 3, 6 and 12 months from treatment initiation.

3, 6, and 12 Month Progression Free Survival

Duration of response is defined as the time of response to the time of progression for those patients who responded. Response is generally defined as either:

Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease.

Only patients with a response are included

Duration of Response

OS is defined from the start of treatment until date of death from any cause or date of last contact with the probability being calculated at 3, 6 and 12 months.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Tivozanib in Recurrent, Platinum-Resistant Ovarian, Fallopian Tube or Primary Peritoneal Cancer	NCT01853644	Recurrent Epith... Recurrent Fallo... Recurrent Prima...	Tivozanib	18 Years - 110 Years	Northwestern University
Tivozanib in Recurrent, Platinum-Resistant Ovarian, Fallopian Tube or Primary Peritoneal Cancer	NCT01853644	Recurrent Epith... Recurrent Fallo... Recurrent Prima...	Tivozanib	18 Years - 110 Years	Northwestern University
Tivozanib in Recurrent, Platinum-Resistant Ovarian, Fallopian Tube or Primary Peritoneal Cancer	NCT01853644	Recurrent Epith... Recurrent Fallo... Recurrent Prima...	Tivozanib	18 Years - 110 Years	Northwestern University

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