Trial Outcomes & Findings for Epothilone B in Treating Patients With CNS Metastases From Breast Cancer (NCT NCT00450866)
NCT ID: NCT00450866
Last Updated: 2014-02-28
Results Overview
The number of patients that are documented to have progression free survival at 3 months after treatment. Progression free is define as \<25% increase in tumor area. PFS will be measured from the date of entry into the trial to the date of documented progression of brain metastases or death.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
55 participants
Primary outcome timeframe
3 months after treatment
Results posted on
2014-02-28
Participant Flow
This was a multicenter conducted at the Cleveland Clinic, University Hospitals Case Medical Center, Massachusetts General Hospital, Memorial Sloan Kettering Cancer Center, and the University of Michigan.Fifty five patients were treated on this study between February 2007 and May 2010, all of whom are considered eligible.
Participant milestones
| Measure |
Epothilone B (Group A)
Group A: Patients with progressive, radiographically measurable parenchymal brain metastases after whole brain radiation therapy (WBRT). Patupilone will be administered as a single intravenous infusion over 20 minutes, once every 3 weeks. Patupilone will be administered at a dose of 10 mg/m2 (q3weeks) with actual body weight.
|
Epothilone B (Group B)
Group B: an exploratory cohort of patients, with either leptomeningeal metastases (LMD) or unirradiated, asymptomatic brain metastasis from breast cancer (BCBM).Patupilone will be administered as a single intravenous infusion over 20 minutes, once every 3 weeks. Patupilone will be administered at a dose of 10 mg/m2 (q3weeks) with actual body weight.
|
|---|---|---|
|
Overall Study
STARTED
|
45
|
10
|
|
Overall Study
COMPLETED
|
38
|
7
|
|
Overall Study
NOT COMPLETED
|
7
|
3
|
Reasons for withdrawal
| Measure |
Epothilone B (Group A)
Group A: Patients with progressive, radiographically measurable parenchymal brain metastases after whole brain radiation therapy (WBRT). Patupilone will be administered as a single intravenous infusion over 20 minutes, once every 3 weeks. Patupilone will be administered at a dose of 10 mg/m2 (q3weeks) with actual body weight.
|
Epothilone B (Group B)
Group B: an exploratory cohort of patients, with either leptomeningeal metastases (LMD) or unirradiated, asymptomatic brain metastasis from breast cancer (BCBM).Patupilone will be administered as a single intravenous infusion over 20 minutes, once every 3 weeks. Patupilone will be administered at a dose of 10 mg/m2 (q3weeks) with actual body weight.
|
|---|---|---|
|
Overall Study
Adverse Event
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
5
|
2
|
|
Overall Study
Death
|
1
|
0
|
|
Overall Study
Physician Decision
|
1
|
0
|
Baseline Characteristics
Epothilone B in Treating Patients With CNS Metastases From Breast Cancer
Baseline characteristics by cohort
| Measure |
Epothilone B (Groups A and B)
n=55 Participants
Epothilone B : Patupilone will be administered as a single intravenous infusion over 20 minutes, once every 3 weeks. Patupilone will be administered at a dose of 10 mg/m2 (q3weeks) with actual body weight.
|
|---|---|
|
Age, Continuous
|
50 years
FULL_RANGE 8.6 • n=93 Participants
|
|
Sex: Female, Male
Female
|
55 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
49 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=93 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Black or African American
|
4 Participants
n=93 Participants
|
|
Race (NIH/OMB)
White
|
48 Participants
n=93 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=93 Participants
|
|
Region of Enrollment
United States
|
55 participants
n=93 Participants
|
|
Central Nervous System (CNS) metastases
Group A
|
45 participants
n=93 Participants
|
|
Central Nervous System (CNS) metastases
Group B
|
10 participants
n=93 Participants
|
PRIMARY outcome
Timeframe: 3 months after treatmentPopulation: Intention to treat
The number of patients that are documented to have progression free survival at 3 months after treatment. Progression free is define as \<25% increase in tumor area. PFS will be measured from the date of entry into the trial to the date of documented progression of brain metastases or death.
Outcome measures
| Measure |
Epothilone B: Group A
n=45 Participants
Group A: Patients with progressive, radiographically measurable parenchymal brain metastases after whole brain radiation therapy (WBRT). Patupilone will be administered as a single intravenous infusion over 20 minutes, once every 3 weeks. Patupilone will be administered at a dose of 10 mg/m2 (q3weeks) with actual body weight.
|
Epothilone B: Group B
n=10 Participants
Group B: an exploratory cohort of patients, with either leptomeningeal metastases (LMD) or unirradiated, asymptomatic brain metastasis from breast cancer (BCBM).Patupilone will be administered as a single intravenous infusion over 20 minutes, once every 3 weeks. Patupilone will be administered at a dose of 10 mg/m2 (q3weeks) with actual body weight.
|
|---|---|---|
|
Central Nervous System (CNS) Progression-free Survival(PFS)
|
12 participants
|
2 participants
|
SECONDARY outcome
Timeframe: 3 months after treatmentPopulation: Intention to treat
Percent of patients that experience the most common grade 3 and above toxicities possibly related to study drug - to be measured using the NCI Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 3.0.
Outcome measures
| Measure |
Epothilone B: Group A
n=55 Participants
Group A: Patients with progressive, radiographically measurable parenchymal brain metastases after whole brain radiation therapy (WBRT). Patupilone will be administered as a single intravenous infusion over 20 minutes, once every 3 weeks. Patupilone will be administered at a dose of 10 mg/m2 (q3weeks) with actual body weight.
|
Epothilone B: Group B
Group B: an exploratory cohort of patients, with either leptomeningeal metastases (LMD) or unirradiated, asymptomatic brain metastasis from breast cancer (BCBM).Patupilone will be administered as a single intravenous infusion over 20 minutes, once every 3 weeks. Patupilone will be administered at a dose of 10 mg/m2 (q3weeks) with actual body weight.
|
|---|---|---|
|
Toxicity as Measured by NCI CTCAE v3.0
|
44 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: 3 months after treatmentPopulation: Intention to treat
Complete Response (CR): the circumstance when the tumor is no longer seen by neuroimaging Partial Response (PR): Decrease of \>50% in the product of two diameters Stable Disease (SD): the circumstance when the scan shows no change. Progression (P): a \> 25% increase in tumor area (two diameters)
Outcome measures
| Measure |
Epothilone B: Group A
n=45 Participants
Group A: Patients with progressive, radiographically measurable parenchymal brain metastases after whole brain radiation therapy (WBRT). Patupilone will be administered as a single intravenous infusion over 20 minutes, once every 3 weeks. Patupilone will be administered at a dose of 10 mg/m2 (q3weeks) with actual body weight.
|
Epothilone B: Group B
n=10 Participants
Group B: an exploratory cohort of patients, with either leptomeningeal metastases (LMD) or unirradiated, asymptomatic brain metastasis from breast cancer (BCBM).Patupilone will be administered as a single intravenous infusion over 20 minutes, once every 3 weeks. Patupilone will be administered at a dose of 10 mg/m2 (q3weeks) with actual body weight.
|
|---|---|---|
|
CNS Response Rate, for Measurable Disease Will be Assessed by the Modified McDonald Criteria
Complete Response (CR)
|
0 participants
|
0 participants
|
|
CNS Response Rate, for Measurable Disease Will be Assessed by the Modified McDonald Criteria
Partial Response (PR)
|
5 participants
|
0 participants
|
|
CNS Response Rate, for Measurable Disease Will be Assessed by the Modified McDonald Criteria
Stable Disease (SD)
|
9 participants
|
2 participants
|
|
CNS Response Rate, for Measurable Disease Will be Assessed by the Modified McDonald Criteria
Progression (P)
|
31 participants
|
8 participants
|
SECONDARY outcome
Timeframe: 3 months after treatmentPopulation: Intention to treat
Complete Response (CR): the circumstance when the tumor is no longer seen by neuroimaging Partial Response (PR): Decrease of \>50% in the product of two diameters Stable Disease (SD): the circumstance when the scan shows no change. Progression (P): a \> 25% increase in tumor area (two diameters)
Outcome measures
| Measure |
Epothilone B: Group A
n=55 Participants
Group A: Patients with progressive, radiographically measurable parenchymal brain metastases after whole brain radiation therapy (WBRT). Patupilone will be administered as a single intravenous infusion over 20 minutes, once every 3 weeks. Patupilone will be administered at a dose of 10 mg/m2 (q3weeks) with actual body weight.
|
Epothilone B: Group B
Group B: an exploratory cohort of patients, with either leptomeningeal metastases (LMD) or unirradiated, asymptomatic brain metastasis from breast cancer (BCBM).Patupilone will be administered as a single intravenous infusion over 20 minutes, once every 3 weeks. Patupilone will be administered at a dose of 10 mg/m2 (q3weeks) with actual body weight.
|
|---|---|---|
|
Systemic Disease Response Rate for Measurable Disease Will be Assessed by the Modified McDonald Criteria
Complete Response (CR)
|
1 participants
|
—
|
|
Systemic Disease Response Rate for Measurable Disease Will be Assessed by the Modified McDonald Criteria
Partial Response (PR)
|
7 participants
|
—
|
|
Systemic Disease Response Rate for Measurable Disease Will be Assessed by the Modified McDonald Criteria
Stable Disease (SD)
|
18 participants
|
—
|
|
Systemic Disease Response Rate for Measurable Disease Will be Assessed by the Modified McDonald Criteria
Progression (P)
|
29 participants
|
—
|
SECONDARY outcome
Timeframe: 48 months from start of studyPopulation: Intention to treat
Median time (months) that patients survived during the duration of the study.
Outcome measures
| Measure |
Epothilone B: Group A
n=55 Participants
Group A: Patients with progressive, radiographically measurable parenchymal brain metastases after whole brain radiation therapy (WBRT). Patupilone will be administered as a single intravenous infusion over 20 minutes, once every 3 weeks. Patupilone will be administered at a dose of 10 mg/m2 (q3weeks) with actual body weight.
|
Epothilone B: Group B
Group B: an exploratory cohort of patients, with either leptomeningeal metastases (LMD) or unirradiated, asymptomatic brain metastasis from breast cancer (BCBM).Patupilone will be administered as a single intravenous infusion over 20 minutes, once every 3 weeks. Patupilone will be administered at a dose of 10 mg/m2 (q3weeks) with actual body weight.
|
|---|---|---|
|
Overall Survival
|
12.7 months
Interval 6.6 to 21.0
|
—
|
Adverse Events
Epothilone B (Groups A and B)
Serious events: 18 serious events
Other events: 55 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Epothilone B (Groups A and B)
n=55 participants at risk
Epothilone B : Patupilone will be administered as a single intravenous infusion over 20 minutes, once every 3 weeks. Patupilone will be administered at a dose of 10 mg/m2 (q3weeks) with actual body weight.
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
1.8%
1/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Nervous system disorders
Aphasia
|
1.8%
1/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Nervous system disorders
Confusion
|
1.8%
1/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
General disorders
Death not associated with CTCAE term - Death NOS (not otherwise specified)
|
1.8%
1/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
General disorders
Death not associated with CTCAE term - Disease progression NOS
|
1.8%
1/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Gastrointestinal disorders
Dehydration
|
10.9%
6/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Gastrointestinal disorders
Diarrhea
|
14.5%
8/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)
|
1.8%
1/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
General disorders
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L) Total
|
1.8%
1/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Gastrointestinal disorders
Hemorrhage, upper GI
|
1.8%
1/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Metabolism and nutrition disorders
Hypokalemia
|
1.8%
1/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Metabolism and nutrition disorders
Hyponatremia
|
1.8%
1/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Gastrointestinal disorders
Ileus, GI (functional obstruction of bowel, i.e., neuroconstipation)
|
1.8%
1/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness, generalized or specific area (not due to neuropathy)
|
1.8%
1/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness, generalized or specific area (not due to neuropathy) - Extremity-lower
|
1.8%
1/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Gastrointestinal disorders
Nausea
|
1.8%
1/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Blood and lymphatic system disorders
Neutropenia
|
1.8%
1/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Gastrointestinal disorders
Pain - Abdomen NOS (not otherwise specified)
|
1.8%
1/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Nervous system disorders
Pain - Head/headache
|
1.8%
1/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Respiratory, thoracic and mediastinal disorders
Pain, thorax (related to persistent coughing)
|
1.8%
1/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Psychiatric disorders
Psychosis (hallucinations/delusions)
|
1.8%
1/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Renal and urinary disorders
Renal Insufficiency
|
1.8%
1/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Nervous system disorders
Syncope (fainting)
|
1.8%
1/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Gastrointestinal disorders
Ulcer, GI - Duodenum
|
1.8%
1/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Gastrointestinal disorders
Vomiting
|
1.8%
1/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Musculoskeletal and connective tissue disorders
Weakness hand, left
|
1.8%
1/55 • Adverse events were collected while patients were on study over a 4 year period.
|
Other adverse events
| Measure |
Epothilone B (Groups A and B)
n=55 participants at risk
Epothilone B : Patupilone will be administered as a single intravenous infusion over 20 minutes, once every 3 weeks. Patupilone will be administered at a dose of 10 mg/m2 (q3weeks) with actual body weight.
|
|---|---|
|
Gastrointestinal disorders
Abdominal Pain
|
27.3%
15/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
16.4%
9/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Blood and lymphatic system disorders
Anemia
|
10.9%
6/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Metabolism and nutrition disorders
Anorexia
|
36.4%
20/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Nervous system disorders
Ataxia
|
7.3%
4/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Gastrointestinal disorders
Constipation
|
29.1%
16/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
12.7%
7/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Gastrointestinal disorders
Dehydration
|
5.5%
3/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Gastrointestinal disorders
Diarrhea
|
81.8%
45/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Nervous system disorders
Dizziness
|
20.0%
11/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Gastrointestinal disorders
Dry mouth/salivary gland (xerostomia)
|
5.5%
3/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
7.3%
4/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)
|
20.0%
11/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Vascular disorders
Edema: limb
|
9.1%
5/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
General disorders
Fatigue (asthenia, lethargy, malaise)
|
87.3%
48/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Gastrointestinal disorders
Flatulence
|
5.5%
3/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Gastrointestinal disorders
Heartburn/dyspepsia
|
14.5%
8/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Investigations
Hypokalemia
|
10.9%
6/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
General disorders
Insomnia
|
5.5%
3/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Nervous system disorders
Memory impairment
|
5.5%
3/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Psychiatric disorders
Mood alteration - Anxiety
|
9.1%
5/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Psychiatric disorders
Mood alteration - Depression
|
5.5%
3/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Gastrointestinal disorders
Mucositis/stomatitis (clinical exam) - Oral cavity
|
12.7%
7/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness, generalized or specific area (not due to neuropathy) - Extremity-lower
|
10.9%
6/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Gastrointestinal disorders
Nausea
|
58.2%
32/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Nervous system disorders
Neuropathy: sensory
|
32.7%
18/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Blood and lymphatic system disorders
Neutropenia
|
7.3%
4/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Musculoskeletal and connective tissue disorders
Pain - Extremity-limb
|
21.8%
12/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Nervous system disorders
Pain - Head/headache
|
32.7%
18/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Musculoskeletal and connective tissue disorders
Pain-Back
|
7.3%
4/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Musculoskeletal and connective tissue disorders
Pain-Bone
|
9.1%
5/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Musculoskeletal and connective tissue disorders
Pain-Joint
|
12.7%
7/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Musculoskeletal and connective tissue disorders
Pain-Muscle
|
14.5%
8/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Skin and subcutaneous tissue disorders
Pruritus/itching
|
5.5%
3/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Skin and subcutaneous tissue disorders
Rash/desquamation
|
10.9%
6/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Gastrointestinal disorders
Sore throat
|
5.5%
3/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Gastrointestinal disorders
Taste alteration (dysgeusia)
|
9.1%
5/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Eye disorders
Visual Changes
|
10.9%
6/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Gastrointestinal disorders
Vomiting
|
36.4%
20/55 • Adverse events were collected while patients were on study over a 4 year period.
|
|
Investigations
Weight loss
|
18.2%
10/55 • Adverse events were collected while patients were on study over a 4 year period.
|
Additional Information
David Peereboom, MD
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Phone: 216-445-6068
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place