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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01853644
Recruitment Status : Active, not recruiting
First Posted : May 15, 2013
Results First Posted : February 28, 2020
Last Update Posted : February 28, 2020
Sponsor:
Collaborator:
National Comprehensive Cancer Network
Information provided by (Responsible Party):
Daniela Matei, Northwestern University

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Recurrent Epithelial Ovarian Cancer
Recurrent Fallopian Tube Cancer
Recurrent Primary Peritoneal Cancer
Intervention Drug: Tivozanib
Enrollment 31
Recruitment Details The study opened to enrollment on May 23,2013 with the first patient being treated on the study on June 6, 2013. The study closed to further enrollment August 10, 2018 with 31 patients registered to the study and 30 patients treated on study.
Pre-assignment Details  
Arm/Group Title Treatment (Tivozanib)
Hide Arm/Group Description

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

Period Title: Registration and Treatment Start
Started 31
Registered 31
Started Treatment 30
Completed 30
Not Completed 1
Reason Not Completed
Did not start treatment             1
Period Title: Reached First Response/Complete 2 Cycles
Started 30
Completed 24
Not Completed 6
Reason Not Completed
Adverse Event             2
Withdrawal by Subject             1
Other             1
Progressive Disease             2
Period Title: Continued Treatment After First Response
Started 24
Completed 12
Not Completed 12
Reason Not Completed
Adverse Event             2
Progressive Diseaes             10
Period Title: Follow up for 3 Years or Until Death
Started [1] 29 [2]
Completed 26
Not Completed 3
Reason Not Completed
Still in the follow up period             3
[1]
1 patient is currently on active treatment and pending follow up period.
[2]
All patients that are treated on the study go into the follow up period
Arm/Group Title Treatment (Tivozanib)
Hide Arm/Group Description

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

Overall Number of Baseline Participants 30
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants
<=18 years
0
   0.0%
Between 18 and 65 years
20
  66.7%
>=65 years
10
  33.3%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants
Female
30
 100.0%
Male
0
   0.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants
Hispanic or Latino
2
   6.7%
Not Hispanic or Latino
28
  93.3%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
2
   6.7%
White
28
  93.3%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 30 participants
30
1.Primary Outcome
Title Overall Response Rate (ORR)
Hide Description

ORR is defined as the percentage 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.

Time Frame Time taken to reach first best response. Range 1-4 cycles (1 cycle = 28 days)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment (Tivozanib)
Hide Arm/Group Description:

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

Overall Number of Participants Analyzed 30
Measure Type: Number
Unit of Measure: participants
4
2.Secondary Outcome
Title Progression Free Survival (PFS) in Platinum-resistant Ovarian Cancer to Treatment With Single Agent Tivozanib
Hide Description 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..
Time Frame Range of months 1-25
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment (Tivozanib)
Hide Arm/Group Description:

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

Overall Number of Participants Analyzed 30
Median (Full Range)
Unit of Measure: months
4
(1 to 25)
3.Secondary Outcome
Title Number of Adverse Events in Platinum-resistant Ovarian Cancer to Treatment With Single Agent Tivozanib
Hide Description 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:
Time Frame During treatment and up to 30 days after completion of study treatment. Range of cycles 1-31 (1 cycle =28 days).
Outcome Measure Data Not Reported
4.Secondary Outcome
Title Overall Survival (OS) in Platinum-resistant Ovarian Cancer to Treatment With Single Agent Tivozanib
Hide Description OS is defined from the start of treatment until date of death from any cause or date of last contact.
Time Frame Range of months 1-39
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment (Tivozanib)
Hide Arm/Group Description:

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

Overall Number of Participants Analyzed 30
Median (Full Range)
Unit of Measure: months
8
(1 to 39)
5.Post-Hoc Outcome
Title Overall Best Response of Patients With Platinum-resistant Ovarian Cancer to Treatment With Single Agent Tivozanib
Hide Description

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.

Time Frame Time taken to reach first best response. Range 1-4 cycles (1 cycle = 28 days)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment (Tivozanib)
Hide Arm/Group Description:

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

Overall Number of Participants Analyzed 30
Measure Type: Count of Participants
Unit of Measure: Participants
CR
0
   0.0%
PR
4
  13.3%
SD
12
  40.0%
PD
11
  36.7%
Not Evaluable
3
  10.0%
6.Post-Hoc Outcome
Title Clinical Benefit Rate (CBR)
Hide Description

CBR is defined as the percentage 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.

Time Frame Time taken to reach first best response. Range 1-4 cycles (1 cycle = 28 days)
Hide Outcome Measure Data
Hide Analysis Population Description
3 patients who were determined to be not evaluable are included in this number
Arm/Group Title Treatment (Tivozanib)
Hide Arm/Group Description:

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

Overall Number of Participants Analyzed 30
Measure Type: Number
Unit of Measure: participants
16
7.Post-Hoc Outcome
Title 6 Month Progression Free Survival Rate
Hide Description PFS rate will be measured by the number of patients that are progression free at 6 months from treatment initiation.
Time Frame 6 months from start of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment (Tivozanib)
Hide Arm/Group Description:

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

Overall Number of Participants Analyzed 30
Measure Type: Number
Unit of Measure: participants
7
Time Frame AEs are collected at the beginning of every cycle (1 Cycle = 28 days) during treatment and for 30 days post last treatment. Range of cycles completed by any patient 1-31 cycles (1 patient currently on treatment, range may change)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Treatment (Tivozanib)
Hide Arm/Group Description

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

All-Cause Mortality
Treatment (Tivozanib)
Affected / at Risk (%)
Total   26/30 (86.67%) 
Hide Serious Adverse Events
Treatment (Tivozanib)
Affected / at Risk (%)
Total   12/30 (40.00%) 
Cardiac disorders   
Sinus tachycardia  1  1/30 (3.33%) 
Gastrointestinal disorders   
Small intestinal obstruction  1  2/30 (6.67%) 
Ileal obstruction  1  1/30 (3.33%) 
Small intestinal perforation  1  2/30 (6.67%) 
Constipation  1  1/30 (3.33%) 
Colonic obstruction  1  1/30 (3.33%) 
Vomiting  1  1/30 (3.33%) 
Abdominal pain  1  1/30 (3.33%) 
Ascites  1  1/30 (3.33%) 
General disorders   
Non-cardiac chest pain  1  1/30 (3.33%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Tumor pain  1  1/30 (3.33%) 
Nervous system disorders   
Stroke  1  1/30 (3.33%) 
1
Term from vocabulary, CTCAE (4.03)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Treatment (Tivozanib)
Affected / at Risk (%)
Total   30/30 (100.00%) 
Blood and lymphatic system disorders   
Anemia  1  12/30 (40.00%) 
Cardiac disorders   
Sinus bradycardia  1  3/30 (10.00%) 
Palpitations  1  2/30 (6.67%) 
Ear and labyrinth disorders   
Hearing impaired  1  2/30 (6.67%) 
Endocrine disorders   
Hypothyroidism  1  3/30 (10.00%) 
Hyperthyroidism  1  1/30 (3.33%) 
Eye disorders   
Blurred vision  1  1/30 (3.33%) 
watery eyes  1  1/30 (3.33%) 
Eye itching  1  1/30 (3.33%) 
Gastrointestinal disorders   
Abdominal distension  1  4/30 (13.33%) 
Abdominal pain  1  14/30 (46.67%) 
Abscess  1  1/30 (3.33%) 
Anal hemorrhage  1  1/30 (3.33%) 
Ascities  1  2/30 (6.67%) 
Bloating  1  6/30 (20.00%) 
Colonic Fistula  1  2/30 (6.67%) 
Constipation  1  7/30 (23.33%) 
Diarrhea  1  16/30 (53.33%) 
Dry mouth  1  4/30 (13.33%) 
Dyspepsia  1  2/30 (6.67%) 
Dysphagia  1  2/30 (6.67%) 
Enterocolitis  1  1/30 (3.33%) 
Flatulence  1  1/30 (3.33%) 
Gastroesophageal reflux disease  1  1/30 (3.33%) 
Gastrointestinal fistula  1  1/30 (3.33%) 
Gastrointestinal pain  1  3/30 (10.00%) 
Mucositis oral  1  4/30 (13.33%) 
Nausea  1  15/30 (50.00%) 
Oral dysesthesia  1  3/30 (10.00%) 
Periodontal disease  1  1/30 (3.33%) 
Rectal hemorrhage  1  1/30 (3.33%) 
Stomach pain  1  1/30 (3.33%) 
Vomiting  1  11/30 (36.67%) 
General disorders   
Chills  1  1/30 (3.33%) 
Edema limbs  1  2/30 (6.67%) 
Fatigue  1  22/30 (73.33%) 
Fever  1  1/30 (3.33%) 
Gait disturbance  1  1/30 (3.33%) 
Polydipsia  1  1/30 (3.33%) 
Night sweats  1  1/30 (3.33%) 
Malaise  1  2/30 (6.67%) 
Non-cardiac chest pain  1  1/30 (3.33%) 
Hepatobiliary disorders   
Portal hypertension  1  1/30 (3.33%) 
Infections and infestations   
Bladder infection  1  1/30 (3.33%) 
Enterocolitis infectious  1  1/30 (3.33%) 
Skin infection  1  1/30 (3.33%) 
Upper respiratory infection  1  3/30 (10.00%) 
Infections and infestations -Urinary tract infection  1  4/30 (13.33%) 
Injury, poisoning and procedural complications   
Bruising  1  2/30 (6.67%) 
Fall  1  1/30 (3.33%) 
Leg injury  1  1/30 (3.33%) 
Investigations   
Activated partial thromboplastin time prolonged  1  1/30 (3.33%) 
Alanine aminotransferase increased  1  5/30 (16.67%) 
Alkaline phosphatase increased  1  12/30 (40.00%) 
Aspartate aminotransferase increased  1  12/30 (40.00%) 
Cholesterol high  1  1/30 (3.33%) 
Creatinine increased  1  2/30 (6.67%) 
Ekectricarduigran QT corrected interval prolonged  1  1/30 (3.33%) 
INR increased  1  2/30 (6.67%) 
Low GFR  1  2/30 (6.67%) 
Elevated TSH  1  1/30 (3.33%) 
Lymphocyte count decreased  1  9/30 (30.00%) 
Neutrophhil count decreased  1  3/30 (10.00%) 
Platelet count decreased  1  8/30 (26.67%) 
Weight loss  1  12/30 (40.00%) 
White blood cell decreased  1  4/30 (13.33%) 
Metabolism and nutrition disorders   
Anorexia  1  16/30 (53.33%) 
Dehydration  1  4/30 (13.33%) 
Hypercalcemia  1  2/30 (6.67%) 
Hyperglycemia  1  6/30 (20.00%) 
Hyperkalemia  1  6/30 (20.00%) 
Hypermagnesemia  1  1/30 (3.33%) 
Hypernatremia  1  1/30 (3.33%) 
Hypertriglyceridemia  1  1/30 (3.33%) 
Hypoalbuminemia  1  12/30 (40.00%) 
Hypocalcemia  1  6/30 (20.00%) 
Hypokalemia  1  9/30 (30.00%) 
Hypomagnesemia  1  13/30 (43.33%) 
Hyponatremia  1  13/30 (43.33%) 
Hypophosphatemia  1  6/30 (20.00%) 
Obesity  1  1/30 (3.33%) 
Musculoskeletal and connective tissue disorders   
Arthralgia  1  11/30 (36.67%) 
Back pain  1  4/30 (13.33%) 
Bone pain  1  1/30 (3.33%) 
Buttock pain  1  1/30 (3.33%) 
Flank pain  1  2/30 (6.67%) 
Generalized muscle weakness  1  4/30 (13.33%) 
Joint range of motion decreased  1  1/30 (3.33%) 
Plantar fascitis  1  1/30 (3.33%) 
Myalgia  1  5/30 (16.67%) 
Neck pain  1  2/30 (6.67%) 
Pain in extremity  1  3/30 (10.00%) 
Nervous system disorders   
Amnesia  1  1/30 (3.33%) 
Dizziness  1  5/30 (16.67%) 
Dysgeusia  1  2/30 (6.67%) 
Headaches  1  9/30 (30.00%) 
Memory impairment  1  1/30 (3.33%) 
Hypersomnia  1  1/30 (3.33%) 
Peripheral sensory neuropathy  1  4/30 (13.33%) 
Paresthesia  1  2/30 (6.67%) 
Tremor  1  2/30 (6.67%) 
Psychiatric disorders   
Agitation  1  1/30 (3.33%) 
Anxiety  1  3/30 (10.00%) 
Confusion  1  6/30 (20.00%) 
Insomnia  1  2/30 (6.67%) 
Strange dreams  1  1/30 (3.33%) 
Renal and urinary disorders   
Hematuria  1  7/30 (23.33%) 
Proteinuria  1  9/30 (30.00%) 
Urinary incontinence  1  3/30 (10.00%) 
Urinary urgency  1  1/30 (3.33%) 
Urinary tract pain  1  2/30 (6.67%) 
Urinary tract obstruction  1  1/30 (3.33%) 
Reproductive system and breast disorders   
Pelvic pain  1  1/30 (3.33%) 
Vaginal hemorrhage  1  4/30 (13.33%) 
Respiratory, thoracic and mediastinal disorders   
Allergic rhinitis  1  1/30 (3.33%) 
Cough  1  5/30 (16.67%) 
Dyspnea  1  8/30 (26.67%) 
Epistaxis  1  2/30 (6.67%) 
Hiccups  1  1/30 (3.33%) 
Hoarseness  1  8/30 (26.67%) 
Pharyngolaryngeal pain  1  1/30 (3.33%) 
Pleural effusion  1  1/30 (3.33%) 
Sore throat  1  1/30 (3.33%) 
Postnasal drip  1  1/30 (3.33%) 
Skin and subcutaneous tissue disorders   
Alopecia  1  1/30 (3.33%) 
Dry skin  1  5/30 (16.67%) 
Nail dicoloration  1  1/30 (3.33%) 
Palmar-plantar erythrodysesthesia syndrome  1  1/30 (3.33%) 
Pruritus  1  2/30 (6.67%) 
Photosensitivity  1  1/30 (3.33%) 
Vascular disorders   
Hypertension  1  21/30 (70.00%) 
Hypotension  1  1/30 (3.33%) 
Thromboembolic event  1  2/30 (6.67%) 
1
Term from vocabulary, CTCAE (4.03)
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Daniela Matei
Organization: Northwestern University
Phone: 312.472.4684
EMail: daniela.matei@northwestern.edu
Layout table for additonal information
Responsible Party: Daniela Matei, Northwestern University
ClinicalTrials.gov Identifier: NCT01853644    
Other Study ID Numbers: STU00073756
First Submitted: May 10, 2013
First Posted: May 15, 2013
Results First Submitted: February 10, 2020
Results First Posted: February 28, 2020
Last Update Posted: February 28, 2020