Trial Outcomes & Findings for Phase II Dasatinib Study in Advanced Breast Cancer (NCT NCT00546104)

NCT ID: NCT00546104

Last Updated: 2013-07-17

Results Overview

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 measurable increase in a non-target lesion, or the appearance of new lesions, or similar definition as appropriate. Proportion progression-free at 16 weeks.From first day of study related treatment with Dasatinib until the date of first documented progression or date of death from any cause, whichever came first.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 31 participants
• Primary outcome timeframe: 16 weeks
• Results posted on: 2013-07-17

Participant Flow

Subjects will be identified in cancer center outpatient clinics multi-site. The study will be introduced by a physician or caregiver known to the patient. We will need to review protected health information in order to identify subjects, and information resulting from this activity will be used only to assess eligibility of a subject.

Meds which inhibit platelet function/coagulation,potent inhibitors of cytochrome CYP3A, or meds that prolong the QT interval during study require a 7 day wash-out.IV bisphosphonates must be held for 2 wks before/6 wks after trial tx. Subjects must be 3 wks since prior to therapy, 2 wks since surgical bx and 3 wks since major surgery.

Participant milestones

Measure	Dasatinib 50-100 mg PO BID
Overall Study STARTED	31
Overall Study COMPLETED	31
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Phase II Dasatinib Study in Advanced Breast Cancer

Baseline characteristics by cohort

Measure	Dasatinib n=31 Participants 50-100mg by mouth twice a day
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	24 Participants n=5 Participants
Age, Categorical >=65 years	7 Participants n=5 Participants
Age Continuous	54.4 years STANDARD_DEVIATION 13.4 • n=5 Participants
Sex: Female, Male Female	31 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Region of Enrollment United States	31 participants n=5 Participants

PRIMARY outcome

Timeframe: 16 weeks

Population: 31 patients on this trial, 1 patient was found to have disease progression at 16-weeks, 16 patients had disease progression prior to 16 weeks, 8 patients were taken off-treatment due to toxicity, and 6 patients voluntarily withdrew from treatment. These latter two groups of patients were censored in the analysis of Progression Free Survival.

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 measurable increase in a non-target lesion, or the appearance of new lesions, or similar definition as appropriate.

Proportion progression-free at 16 weeks.From first day of study related treatment with Dasatinib until the date of first documented progression or date of death from any cause, whichever came first.

Outcome measures

Measure	Dasatinib n=31 Participants 50mg-100mg po BID
Estimation of the Proportion of Progression-free Patients at 16 Wks.	0 percentage of participants Interval 0.0 to 20.0

SECONDARY outcome

Timeframe: 16 weeks

Population: Proportion with Best Response of Stable Disease

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progression At least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as a reference the smallest sum longest diameter recorded since treatment started, or the appearance of one or more new lesions.

RECIST 1.0 Overall response:

Complete Response (CR) Partial Response (PR) Stable Disease (SD) Progressive Disease (PD)

CR= CR+CR and No new lesions PR= CR+SD; PR+SD and no new lesions SD= SD+SD and no new lesions PD= PD+any new lesions

Outcome measures

Measure	Dasatinib n=30 Participants 50mg-100mg po BID
To Measure Response to Protocol Therapy Per RECIST Criteria	16.7 percentage of participants

SECONDARY outcome

Timeframe: 4 weeks

Population: Twenty patients with evaluable biopsies at baseline and 4 week follow-up

For the 20 patients with evaluable biopsies at baseline and week 4, the median relative change from baseline in tissue biomarker levels of phospho-Src (p-Src)

Outcome measures

Measure	Dasatinib n=20 Participants 50mg-100mg po BID
Characterization and Comparison of SRC (A Protein Tyrosine Kinase)Dysregulation at Baseline (All Patients), After 4 Weeks of Dasatinib Treatment (All Patients), and at Progression (Only Patients Who Progress After Documented Response)	-0.125 percentage of change in p-SRC Interval -0.41 to 0.153

SECONDARY outcome

Timeframe: 16 weeks

Population: 20 patients with baseline and 4 week Src measures. 11 patients came off due to screen failure, toxicity or progression before 4 week biopsy.

Since all patients progressed there is no comparison to between responders and non-responders.

Outcome measures

Measure	Dasatinib n=20 Participants 50mg-100mg po BID
Correlate SRC Dysregulation Results With Response to Dasatinib Therapy	-.10 percentage change in p-SRC Interval -0.3 to 0.1

SECONDARY outcome

Timeframe: Baseline Src measure to first progression

Population: 11 patients had both change in Src level and progression time intervals

Spearman's correlation between the change in SRC signature from baseline to 4 weeks and time to progression

Outcome measures

Measure	Dasatinib n=11 Participants 50mg-100mg po BID
To Explore the Association Between Each Patient's SRC Signature and Their Time to Progression.	0.27 correlation coefficient

SECONDARY outcome

Timeframe: not assessed

Not assessed secondary to limited number of subjects.

Outcome measures

Outcome data not reported

Adverse Events

Dasatinib

Serious events: 10 serious events

Other events: 30 other events

Deaths: 0 deaths

Serious adverse events

Measure	Dasatinib n=31 participants at risk 50-100mg po bid
Respiratory, thoracic and mediastinal disorders Pneumonitis	3.2% 1/31
Blood and lymphatic system disorders Thrombosis	3.2% 1/31
General disorders hyponatremia	3.2% 1/31
Infections and infestations infection	3.2% 1/31
Gastrointestinal disorders diarrhea	3.2% 1/31
General disorders fever	3.2% 1/31
General disorders Pain	6.5% 2/31
General disorders Pain, back	3.2% 1/31
General disorders Pain, extrimity limb	3.2% 1/31
Respiratory, thoracic and mediastinal disorders Dyspnea	6.5% 2/31
Metabolism and nutrition disorders Anorexia	3.2% 1/31
General disorders Syncope	3.2% 1/31
Blood and lymphatic system disorders Edema, limb	3.2% 1/31
Hepatobiliary disorders AST	3.2% 1/31
Respiratory, thoracic and mediastinal disorders Pleural Effusion	9.7% 3/31
General disorders Pain, chest/thorax	3.2% 1/31

Other adverse events

Measure	Dasatinib n=31 participants at risk 50-100mg po bid
General disorders anorexia	41.9% 13/31 • Number of events 13
General disorders fatigue	51.6% 16/31 • Number of events 16
Gastrointestinal disorders fever: non-neutropenic	16.1% 5/31 • Number of events 5
General disorders Flushing	22.6% 7/31 • Number of events 7
General disorders insomnia	25.8% 8/31 • Number of events 8
Gastrointestinal disorders diarrhea	48.4% 15/31 • Number of events 15
Gastrointestinal disorders constipation	35.5% 11/31 • Number of events 11
Gastrointestinal disorders nausea	61.3% 19/31 • Number of events 19
Gastrointestinal disorders vomiting	41.9% 13/31 • Number of events 13
Respiratory, thoracic and mediastinal disorders cough	19.4% 6/31 • Number of events 6
Respiratory, thoracic and mediastinal disorders dyspnea	38.7% 12/31 • Number of events 12
Respiratory, thoracic and mediastinal disorders pneumonitis	9.7% 3/31 • Number of events 3
Respiratory, thoracic and mediastinal disorders paricardial effusion	6.5% 2/31 • Number of events 2
Gastrointestinal disorders pain: abdomen	19.4% 6/31 • Number of events 6
Musculoskeletal and connective tissue disorders pain: bone	19.4% 6/31 • Number of events 6
Skin and subcutaneous tissue disorders pain: chestwall	12.9% 4/31 • Number of events 4
Musculoskeletal and connective tissue disorders pain:extremity	19.4% 6/31 • Number of events 6
Nervous system disorders pain: headache	35.5% 11/31 • Number of events 11
Musculoskeletal and connective tissue disorders pain:joint	29.0% 9/31 • Number of events 9
Musculoskeletal and connective tissue disorders pain: muscle	12.9% 4/31 • Number of events 4
Hepatobiliary disorders elevated ALT	16.1% 5/31 • Number of events 5
Hepatobiliary disorders elevated AST	12.9% 4/31 • Number of events 4
Investigations hyponatremia	6.5% 2/31 • Number of events 2
Investigations thrombocytopenia	6.5% 2/31 • Number of events 2
Vascular disorders DVT	6.5% 2/31 • Number of events 2
General disorders edema:facial	16.1% 5/31 • Number of events 5
General disorders edema: extremity	19.4% 6/31 • Number of events 6
Skin and subcutaneous tissue disorders cellulitis	3.2% 1/31 • Number of events 1
Skin and subcutaneous tissue disorders rash	51.6% 16/31 • Number of events 16
Skin and subcutaneous tissue disorders mucositis	12.9% 4/31 • Number of events 4
General disorders rhinitis	16.1% 5/31 • Number of events 5
Nervous system disorders neuropathy sensory	29.0% 9/31 • Number of events 9
Respiratory, thoracic and mediastinal disorders plueral effusion	51.6% 16/31 • Number of events 16

Additional Information

Kimberly Blackwell, MD

Duke University Health System

Phone: 919-668-1478

Email: kimberly.blackwell@duke.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place