Trial Outcomes & Findings for Tivantinib in Treating Patients With Recurrent or Metastatic Breast Cancer (NCT NCT01575522)

Results Overview

Analyzed using the Kaplan-Meier method. 95% confidence intervals (CI) will be determined. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), 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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

22 participants

Primary outcome timeframe

Time from start of treatment to time of progression or death, assessed up to 6 months

Results posted on

2016-03-21

Participant Flow

Participant milestones

Participant milestones
Measure	Treatment (Tivantinib) Patients receive tivantinib 360 mg PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection at baseline and periodically during study for c-Met expression, relevant markers (HGF and VEGF), PTEN loss, and PI3K mutation analysis by FISH and IHC. Archived tumor tissue samples are also analyzed. Laboratory Biomarker Analysis: Correlative studies Tivantinib: Given PO
Overall Study STARTED	22
Overall Study COMPLETED	22
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Tivantinib in Treating Patients With Recurrent or Metastatic Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Tivantinib) n=22 Participants Patients receive tivantinib PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection at baseline and periodically during study for c-Met expression, relevant markers (HGF and VEGF), PTEN loss, and PI3K mutation analysis by FISH and IHC. Archived tumor tissue samples are also analyzed. Laboratory Biomarker Analysis: Correlative studies Tivantinib: Given PO
Age, Continuous	55 years STANDARD_DEVIATION 10 • n=5 Participants
Sex: Female, Male Female	22 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Race/Ethnicity, Customized White	20 participants n=5 Participants
Race/Ethnicity, Customized Black or African American	2 participants n=5 Participants

PRIMARY outcome

Timeframe: Time from start of treatment to time of progression or death, assessed up to 6 months

Analyzed using the Kaplan-Meier method. 95% confidence intervals (CI) will be determined. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), 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.

Outcome measures

Outcome measures
Measure	Treatment (Tivantinib) n=22 Participants Patients receive tivantinib PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection at baseline and periodically during study for c-Met expression, relevant markers (HGF and VEGF), PTEN loss, and PI3K mutation analysis by FISH and IHC. Archived tumor tissue samples are also analyzed. Laboratory Biomarker Analysis: Correlative studies Tivantinib: Given PO
PFS Status	1.2 months Interval 1.0 to 1.4

SECONDARY outcome

Timeframe: Up to 1 year

The 95% confidence intervals should be provided. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by Conventional CT or 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.

Outcome measures

Outcome measures
Measure	Treatment (Tivantinib) n=22 Participants Patients receive tivantinib PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection at baseline and periodically during study for c-Met expression, relevant markers (HGF and VEGF), PTEN loss, and PI3K mutation analysis by FISH and IHC. Archived tumor tissue samples are also analyzed. Laboratory Biomarker Analysis: Correlative studies Tivantinib: Given PO
Overall Response Using RECIST v1.1	4.5 percentage of participants Interval 0.1 to 22.8

SECONDARY outcome

Timeframe: Baseline

Assessment of ploidy status was done by visual screening of all tumor area; cells with maximum number of signals were recorded. MET amplification was defined as a MET/CEP7 ratio ≥ 2. Samples having a MET/CEP7 ratio from 1.5 and up to 2 were defined as having relative MET gain. Samples with a MET/CEP7 ratio of 1 but with more than two copies of each probe were defined as having polysomy of chromosome 7.

Outcome measures

Outcome measures
Measure	Treatment (Tivantinib) n=22 Participants Patients receive tivantinib PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection at baseline and periodically during study for c-Met expression, relevant markers (HGF and VEGF), PTEN loss, and PI3K mutation analysis by FISH and IHC. Archived tumor tissue samples are also analyzed. Laboratory Biomarker Analysis: Correlative studies Tivantinib: Given PO
To Evaluate c-Met Expression in Archival Tumor Tissue.	10 participants

SECONDARY outcome

Timeframe: Baseline

MET amplification was defined as a MET/CEP7 ratio ≥ 2. Samples having a MET/CEP7 ratio from 1.5 and up to 2 were defined as having relative MET gain. Samples with a MET/CEP7 ratio of 1 but with more than two copies of each probe were defined as having polysomy of chromosome 7.

Outcome measures

Outcome measures
Measure	Treatment (Tivantinib) n=22 Participants Patients receive tivantinib PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection at baseline and periodically during study for c-Met expression, relevant markers (HGF and VEGF), PTEN loss, and PI3K mutation analysis by FISH and IHC. Archived tumor tissue samples are also analyzed. Laboratory Biomarker Analysis: Correlative studies Tivantinib: Given PO
To Evaluate Phospho c-Met Expression in Archival Tumor Tissue.	0 participants

SECONDARY outcome

Timeframe: Baseline

Outcome measures

Outcome measures
Measure	Treatment (Tivantinib) n=7 Participants Patients receive tivantinib PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection at baseline and periodically during study for c-Met expression, relevant markers (HGF and VEGF), PTEN loss, and PI3K mutation analysis by FISH and IHC. Archived tumor tissue samples are also analyzed. Laboratory Biomarker Analysis: Correlative studies Tivantinib: Given PO
To Evaluate the Incidence of c-Met Positive Circulating Tumor Cells.	1 participants

Adverse Events

Treatment (Tivantinib)

Serious events: 13 serious events

Other events: 22 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Treatment (Tivantinib) n=22 participants at risk Patients receive tivantinib PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection at baseline and periodically during study for c-Met expression, relevant markers (HGF and VEGF), PTEN loss, and PI3K mutation analysis by FISH and IHC. Archived tumor tissue samples are also analyzed. Laboratory Biomarker Analysis: Correlative studies Tivantinib: Given PO
Respiratory, thoracic and mediastinal disorders Pleural effusion	4.5% 1/22 • Number of events 1 • April 2012 -
Respiratory, thoracic and mediastinal disorders Cough	4.5% 1/22 • Number of events 1 • April 2012 -
Respiratory, thoracic and mediastinal disorders Dyspnea	13.6% 3/22 • Number of events 3 • April 2012 -
Psychiatric disorders Anxiety	4.5% 1/22 • Number of events 1 • April 2012 -
Skin and subcutaneous tissue disorders Cellulitis	4.5% 1/22 • Number of events 1 • April 2012 -
Gastrointestinal disorders Constipation	4.5% 1/22 • Number of events 1 • April 2012 -
Investigations Neutropenia	4.5% 1/22 • Number of events 3 • April 2012 -
Vascular disorders Thromboembolic event	4.5% 1/22 • Number of events 1 • April 2012 -
General disorders Death	13.6% 3/22 • Number of events 3 • April 2012 -

Other adverse events

Other adverse events
Measure	Treatment (Tivantinib) n=22 participants at risk Patients receive tivantinib PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection at baseline and periodically during study for c-Met expression, relevant markers (HGF and VEGF), PTEN loss, and PI3K mutation analysis by FISH and IHC. Archived tumor tissue samples are also analyzed. Laboratory Biomarker Analysis: Correlative studies Tivantinib: Given PO
General disorders Fatigue	72.7% 16/22 • Number of events 16 • April 2012 -
Gastrointestinal disorders Nausea	31.8% 7/22 • Number of events 7 • April 2012 -
Blood and lymphatic system disorders Anemia	27.3% 6/22 • Number of events 6 • April 2012 -
Gastrointestinal disorders Diarrhea	27.3% 6/22 • Number of events 6 • April 2012 -
Blood and lymphatic system disorders Neutropenia	22.7% 5/22 • Number of events 5 • April 2012 -
Metabolism and nutrition disorders Anorexia	18.2% 4/22 • Number of events 4 • April 2012 -
Skin and subcutaneous tissue disorders Rash maculo-papular	13.6% 3/22 • Number of events 3 • April 2012 -
Gastrointestinal disorders Vomiting	9.1% 2/22 • Number of events 2 • April 2012 -

Additional Information

Sara M. Tolaney, MD, MPH

Dana-Farber Cancer Institute

Phone: 617.632.5743

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60