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Recurrent Epithelial Ovarian CancerPhase 2TIVONCT01853644

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

A Phase 2 study testing Tivozanib in people with Recurrent Epithelial Ovarian Cancer and Recurrent Fallopian Tube Cancer, run by Northwestern University at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 110 years, women only
What is being tested?
Tivozanib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
31 participants
Where
2 sitesUnited States
Study dates
6 Jun 2013to 11 May 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 110 years
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • • Patients must have recurrent or persistent, platinum resistant epithelial ovarian, fallopian tube or primary peritoneal carcinoma; platinum-resistant disease is defined as a recurrence within 6 months of completing adjuvant, platinum-based chemotherapy
  • Patients must have measurable disease or non-measurable (detectable) 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 greater than or equal to 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI) or by clinical exam; or greater than or equal to 20 mm when measured by chest x-ray; lymph nodes must be greater than or equal to 15 mm in short axis when measured by CT or MRI
  • Non-measurable (detectable) disease in a patient is defined in this protocol as one who does not have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) criteria but does have a cancer antigen 125 (CA-125) greater than or equal to two times the upper normal limit within the last 60 days (confirmatory at baseline) and at least one of the following conditions:
  • Ascites and/or pleural effusion attributed to tumor
  • Hypermetabolic lesions on positron emission tomography (PET) scan
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  • Patients with measurable disease must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST
  • Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
  • 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 other prior therapy directed at the malignant tumor, including chemotherapy, biological/targeted (non-cytotoxic) agents and immunologic agents, must be discontinued at least three weeks prior to registration
  • At least 4 weeks must have elapsed since the patient underwent any major surgery (e.g., major: laparotomy, laparoscopy, thoracotomy, video assisted thorascopic surgery (VATS); there is no restriction on minor procedures (e.g., minor: central venous access catheter placement, ureteral stent placement or exchange, paracentesis, thoracentesis)
  • Patients must have had one prior taxane and platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organo platinum compound; this initial treatment may have included intraperitoneal therapy, consolidation, non-cytotoxic (biologic/targeted agents, such as bevacizumab) or extended therapy administered after surgical or non-surgical assessment; there is no maximum number of prior regimens;
  • patients may not have had any prior systemic therapy (including interleukin-2, interferon-alpha, chemotherapy, bevacizumab, investigational or licensed drug that targets vascular endothelial growth factor [VEGF] or VEGF receptors/pathway or are mammalian target of rapamycin [mTOR] inhibitors) for treatment of recurrent ovarian cancer
  • Patients must have signed an approved informed consent and authorization permitting the release of personal health information
  • Patients must meet pre-entry requirements
  • A female is eligible to participate if she is of non-childbearing potential or as documentation of a negative pregnancy test prior to the start of the study treatment; sexually active pre-menopausal female subjects must agree to use adequate, highly effective contraceptive measures, while on study and for 45 days after the last dose of last study drug; effective birth control includes (a) intrauterine device (IUD) plus one barrier method; (b) oral, implantable or injectable contraceptives plus one barrier method; or (c) 2 barrier methods; effective barrier methods are male or female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm)

Who cannot join

  • • Age < 18 years
  • Patients who have had previous treatment with tivozanib
  • Hemoglobin < 9.0 g/dL
  • Absolute neutrophil count (ANC) < 1500 per mm^3
  • Platelet count < 100,000 per mm^3
  • Total bilirubin > 1.5 × upper limit of normal (ULN) (or > 2.5 x ULN for subjects with asymptomatic Gilbert's syndrome)
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  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 × ULN (or > 5 × ULN for subjects with liver metastasis)
  • BOTH total bilirubin > ULN AND AST/ALT > ULN
  • Alkaline phosphatase > 2.5 × ULN (or > 5 × ULN for subjects with liver or bone metastasis)
  • Creatinine > 2.0 × ULN
  • Prothrombin time (PT) such that international normalized ratio (INR) > 1.5 x ULN (unless a patient is on therapeutic warfarin) or a partial thromboplastin time (PTT) > 1.5 x ULN
  • Proteinuria > 3+ by urinalysis or urine dipstick
  • Significant cardiovascular disease, including:
  • Symptomatic left ventricular dysfunction or baseline left ventricular ejection fraction (LVEF) by multigated acquisition scan (MUGA) or echocardiogram (ECHO) of =< lower limit of institutional normal (LLN)
  • Uncontrolled hypertension: systolic blood pressure of > 140 mmHg or diastolic blood pressure of > 90 mmHg documented on 2 consecutive measurements taken at least 24 hours apart
  • Myocardial infarction, severe angina, or unstable angina within 6 months prior to administration of first dose of study drug
  • History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation)
  • Cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well controlled with anti-arrhythmic medication)
  • Coronary or peripheral artery bypass graft within 6 months of screening
  • History of class III or IV congestive heart failure, as defined by the New York Heart Association
  • Central nervous system metastases; Note: subjects with previously treated (radiotherapy or surgery) brain metastasis that have been stable without steroid treatment for at least 3 months following prior treatment may be enrolled
  • Non-healing wound, bone fracture, or skin ulcer
  • Active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis, or other gastrointestinal condition with increased risk of perforation; history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 4 weeks prior to administration of first dose of study drug
  • Serious/active infection or infection requiring parenteral antibiotics
  • Corrected QT interval (QTc) of > 480 msec using Bazett's formula
  • Radiotherapy or minor surgical procedure within 2 weeks, or major surgical procedure within 4 weeks prior to administration of first dose of study drug; inadequate recovery from prior surgical procedure
  • Significant thromboembolic or vascular disorders within 6 months prior to administration of first dose of study drug, including but not limited to:
  • Deep vein thrombosis
  • Pulmonary embolism
  • Cerebrovascular accident (CVA) or transient ischemic attack (TIA)
  • Peripheral arterial ischemia > grade 2 (per National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version 4.0)
  • Significant bleeding disorders within 6 months prior to administration of first dose of study drug, including but not limited to:
  • Hematemesis, hematochezia, melena or other gastrointestinal bleeding >= grade 2 (per CTCAE version 4.0)
  • Hemoptysis or other pulmonary bleeding >= grade 2 (per CTCAE Version 4.0)
  • Hematuria or other genitourinary bleeding >= grade 2 (per CTCAE Version 4.0)
  • Currently active second primary malignancy, including hematologic malignancies (leukemia, lymphoma, multiple myeloma, etc.), other than non-melanoma skin cancers, non-metastatic prostate cancer, in situ cervical cancer, and ductal or lobular carcinoma in situ of the breast; subjects are considered to have a currently active malignancy if they have completed anti-cancer therapy and have not been disease free for > 2 years
  • Pregnant or lactating females
  • History of genetic or acquired immune suppression disease such as human immunodeficiency virus (HIV); subjects on immune suppressive therapy for organ transplant
  • Life-threatening illness or organ system dysfunction compromising safety evaluation
  • Requirement for hemodialysis or peritoneal dialysis
  • Inability to swallow capsules, malabsorption syndrome or gastrointestinal disease that severely affects the absorption of study drugs, major resection of the stomach or small bowel, or gastric bypass procedure
  • Known hypersensitivity to drugs chemically related to tivozanib hydrochloride or sunitinib or their excipients
  • Psychiatric disorder or altered mental status precluding informed consent or protocol-related testing

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Northwestern University

    Chicago, Illinois, 60611

  • CDH-Delnor Health System - Northwestern Medicine Cancer Center

    Warrenville, Illinois, 60555

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

  1. 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.

Being tested
Tivozanib
Keywords
Cancer, Recurrent, Ovary, Fallopian Tube, Primary Peritioneal, Phase II, Platinum Resistant
Medical subject headings
Carcinoma, Ovarian Epithelial, Fallopian Tube Neoplasms, Neoplasms, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TivozanibDrug

    Also called AV-951, Oral VEGF receptor tyrosine kinase inhibitor AV-951

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

Study groups in NCT01853644
Study groupRoleWhat they receive
Treatment (Tivozanib)ExperimentalTivozanib 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
Receives: Drug: Tivozanib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Response Rate (ORR)

    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.

    Measured: Time taken to reach first best response. Range 1-4 cycles (1 cycle = 28 days)

Secondary outcomes (3)

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

    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..

    Measured: Up to 36 months

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

    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.

    Measured: During treatment and up to 30 days after completion of study treatment. Range of cycles 1-32 (1 cycle =28 days).

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

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

    Measured: Up to approximately 42 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 May 2013 (estimated)
  2. Study start6 Jun 2013
  3. Primary completion2 Oct 2018
  4. Study completion11 May 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
31 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01853644
Sponsor's protocol ID
STU00073756
Acronym
TIVO
Status last verified
Sep 2021
First submitted
10 May 2013
Last updated
12 Oct 2021
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Tivozanib in people with Recurrent Epithelial Ovarian Cancer and Recurrent Fallopian Tube Cancer, run by Northwestern University at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 43 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Feb 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Response Rate (ORR) (time frame: Time taken to reach first best response. Range 1-4 cycles (1 cycle = 28 days)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01853644.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Oct 2021.

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