Trial Outcomes & Findings for ONTAK® in Treating Patients With Advanced Breast Cancer That Did Not Respond to Previous Treatment (NCT NCT00425672)
NCT ID: NCT00425672
Last Updated: 2018-12-05
Results Overview
Subjects are monitored for the development of end organ damage by assessing adverse events with serum chemistries, liver function studies, serum albumin, complete blood counts, symptom assessment, and physical exams performed at every cycle until 3 weeks after the final dose of ONTAK. All adverse events for all systems are graded on a scale of 1-5 using CTCAE v3.0.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
15 participants
Primary outcome timeframe
7 Days after last dose of ONTAK
Results posted on
2018-12-05
Participant Flow
Participant milestones
| Measure |
ONTAK
Patients receive ONTAK IV over 1 hour on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
ONTAK: Given IV
flow cytometry: Correlative studies
immunohistochemistry staining method: Correlative studies
enzyme-linked immunosorbent assay: Correlative studies
laboratory biomarker analysis: Correlative studies
protein expression analysis: Correlative studies
|
|---|---|
|
Overall Study
STARTED
|
15
|
|
Overall Study
COMPLETED
|
14
|
|
Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
ONTAK® in Treating Patients With Advanced Breast Cancer That Did Not Respond to Previous Treatment
Baseline characteristics by cohort
| Measure |
Arm I
n=15 Participants
Patients receive ONTAK IV over 1 hour on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
ONTAK: Given IV
flow cytometry: Correlative studies
immunohistochemistry staining method: Correlative studies
enzyme-linked immunosorbent assay: Correlative studies
laboratory biomarker analysis: Correlative studies
protein expression analysis: Correlative studies
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
13 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
2 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
14 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
13 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
15 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 7 Days after last dose of ONTAKSubjects are monitored for the development of end organ damage by assessing adverse events with serum chemistries, liver function studies, serum albumin, complete blood counts, symptom assessment, and physical exams performed at every cycle until 3 weeks after the final dose of ONTAK. All adverse events for all systems are graded on a scale of 1-5 using CTCAE v3.0.
Outcome measures
| Measure |
Arm I
n=15 Participants
Patients receive ONTAK IV over 1 hour on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
ONTAK: Given IV
flow cytometry: Correlative studies
immunohistochemistry staining method: Correlative studies
enzyme-linked immunosorbent assay: Correlative studies
laboratory biomarker analysis: Correlative studies
protein expression analysis: Correlative studies
|
|---|---|
|
Safety Evaluated by Collecting Study Related Toxicity as Assessed by CTCAE v3.0
|
15 Participants
|
PRIMARY outcome
Timeframe: 21 days after cycle 6Population: 14 patients equals patients that had repeat blood draws taken but did not complete the treatment except for 4 patients who completed the study
The efficacy of ONTAK in depleting Tregs will be defined as a decrease in peripheral blood Tregs by 25% of each individual subject's baseline. All subjects will undergo blood draws at baseline and post ONTAK infusions at designated time points. Tregs from the peripheral blood will be quantitated using flow cytometry.
Outcome measures
| Measure |
Arm I
n=14 Participants
Patients receive ONTAK IV over 1 hour on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
ONTAK: Given IV
flow cytometry: Correlative studies
immunohistochemistry staining method: Correlative studies
enzyme-linked immunosorbent assay: Correlative studies
laboratory biomarker analysis: Correlative studies
protein expression analysis: Correlative studies
|
|---|---|
|
Efficacy of ONTAK in Depleting T-regulatory Cells as a Decrease in Peripheral Blood Tregs Using Flow Cytometry
|
4 Participants
|
SECONDARY outcome
Timeframe: 21 days after cycle 6The incidence of IL-2 expression and its receptor complex, IL-2R in tumor samples will be evaluated by IHC analysis. Tumor sections will be interpreted as either positive or negative.
Outcome measures
| Measure |
Arm I
n=14 Participants
Patients receive ONTAK IV over 1 hour on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
ONTAK: Given IV
flow cytometry: Correlative studies
immunohistochemistry staining method: Correlative studies
enzyme-linked immunosorbent assay: Correlative studies
laboratory biomarker analysis: Correlative studies
protein expression analysis: Correlative studies
|
|---|---|
|
Incidence of Interleukin-2 (IL-2) and IL-2 Receptor (IL-2R) Expression in Tumor Samples by Immunohistochemical (IHC) Analysis
YES
|
8 Participants
|
|
Incidence of Interleukin-2 (IL-2) and IL-2 Receptor (IL-2R) Expression in Tumor Samples by Immunohistochemical (IHC) Analysis
NO
|
6 Participants
|
SECONDARY outcome
Timeframe: 21 days after cycle 6Population: 4/14 patients had peripheral blood available before and after ONTAK treatment.
Evaluate levels of circulating sIL-2R (pg/ml) in the peripheral blood assessed before and after ONTAK therapy. Changes from baseline will be tabulated.
Outcome measures
| Measure |
Arm I
n=14 Participants
Patients receive ONTAK IV over 1 hour on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
ONTAK: Given IV
flow cytometry: Correlative studies
immunohistochemistry staining method: Correlative studies
enzyme-linked immunosorbent assay: Correlative studies
laboratory biomarker analysis: Correlative studies
protein expression analysis: Correlative studies
|
|---|---|
|
Presence of Circulating sIL-2R in the Peripheral Blood
Pre ONTAK Treatment
|
4.8 pg/ml
Interval 1.3 to 673.0
|
|
Presence of Circulating sIL-2R in the Peripheral Blood
6 Weeks Post ONTAK Treatment
|
8.1 pg/ml
Interval 3.0 to 360.5
|
|
Presence of Circulating sIL-2R in the Peripheral Blood
12-16 Weeks Post ONTAK Treatment
|
34.8 pg/ml
Interval 3.4 to 58.1
|
|
Presence of Circulating sIL-2R in the Peripheral Blood
18-23 Weeks Post ONTAK Treatment
|
17.7 pg/ml
Interval 2.7 to 282.5
|
SECONDARY outcome
Timeframe: 21 days after cycle 6Evaluate the effect of ONTAK on endogenous tumor specific immunity
Outcome measures
| Measure |
Arm I
n=14 Participants
Patients receive ONTAK IV over 1 hour on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
ONTAK: Given IV
flow cytometry: Correlative studies
immunohistochemistry staining method: Correlative studies
enzyme-linked immunosorbent assay: Correlative studies
laboratory biomarker analysis: Correlative studies
protein expression analysis: Correlative studies
|
|---|---|
|
Presence of Endogenous Tumor-specific Immunity
|
10 Participants
|
SECONDARY outcome
Timeframe: 21 days after cycle 6Anti-tumor effects of ONTAK will be determined by evaluating tumor response and progression per RECIST. An objective response to ONTAK will be defined as achieving a CR or PR. Analysis of the data will include determination of complete (CR) and partial response (PR) rates, as well as stable (SD) and progressive disease (PD).
Outcome measures
| Measure |
Arm I
n=15 Participants
Patients receive ONTAK IV over 1 hour on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
ONTAK: Given IV
flow cytometry: Correlative studies
immunohistochemistry staining method: Correlative studies
enzyme-linked immunosorbent assay: Correlative studies
laboratory biomarker analysis: Correlative studies
protein expression analysis: Correlative studies
|
|---|---|
|
Anti-tumor Effects of ONTAK Determined by Tumor Response and Progression
Complete Response (CR)
|
0 Participants
|
|
Anti-tumor Effects of ONTAK Determined by Tumor Response and Progression
Partial Response (PR)
|
0 Participants
|
|
Anti-tumor Effects of ONTAK Determined by Tumor Response and Progression
Progressive Disease (PD)
|
10 Participants
|
|
Anti-tumor Effects of ONTAK Determined by Tumor Response and Progression
Stable Disease (SD)
|
4 Participants
|
Adverse Events
Arm I
Serious events: 1 serious events
Other events: 15 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Arm I
n=15 participants at risk
Patients receive ONTAK IV over 1 hour on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
ONTAK: Given IV
flow cytometry: Correlative studies
immunohistochemistry staining method: Correlative studies
enzyme-linked immunosorbent assay: Correlative studies
laboratory biomarker analysis: Correlative studies
protein expression analysis: Correlative studies
|
|---|---|
|
Gastrointestinal disorders
Severe Nausea and Vomiting
|
6.7%
1/15 • Number of events 1
|
Other adverse events
| Measure |
Arm I
n=15 participants at risk
Patients receive ONTAK IV over 1 hour on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
ONTAK: Given IV
flow cytometry: Correlative studies
immunohistochemistry staining method: Correlative studies
enzyme-linked immunosorbent assay: Correlative studies
laboratory biomarker analysis: Correlative studies
protein expression analysis: Correlative studies
|
|---|---|
|
Investigations
Allergic Reaction/Hypersensitivity
|
6.7%
1/15 • Number of events 1
|
|
Ear and labyrinth disorders
Tinnitus
|
6.7%
1/15 • Number of events 1
|
|
Ear and labyrinth disorders
Other - Ringing in Ear
|
6.7%
1/15 • Number of events 1
|
|
Blood and lymphatic system disorders
Hemoglobin Abnormal
|
53.3%
8/15 • Number of events 18
|
|
Blood and lymphatic system disorders
Lymphopenia
|
26.7%
4/15 • Number of events 8
|
|
Blood and lymphatic system disorders
Platelets Abnormal
|
20.0%
3/15 • Number of events 6
|
|
Blood and lymphatic system disorders
Leukocytes Abnormal
|
13.3%
2/15 • Number of events 7
|
|
Blood and lymphatic system disorders
ANC/AGC Abnormal
|
13.3%
2/15 • Number of events 3
|
|
Blood and lymphatic system disorders
Blood and Lymphatic System Disorders - Other
|
6.7%
1/15 • Number of events 2
|
|
Cardiac disorders
Cardiac Arrhythmia
|
6.7%
1/15 • Number of events 2
|
|
Vascular disorders
Hypotension
|
13.3%
2/15 • Number of events 4
|
|
Cardiac disorders
Hypertension
|
6.7%
1/15 • Number of events 2
|
|
General disorders
Fatigue
|
80.0%
12/15 • Number of events 36
|
|
General disorders
Rigors/Chills
|
73.3%
11/15 • Number of events 12
|
|
Psychiatric disorders
Insomnia
|
66.7%
10/15 • Number of events 14
|
|
General disorders
Fever
|
26.7%
4/15 • Number of events 5
|
|
Gastrointestinal disorders
Weight Gain
|
6.7%
1/15 • Number of events 2
|
|
Gastrointestinal disorders
Weight Loss
|
6.7%
1/15 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Rash/Desquamation
|
13.3%
2/15 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Rash: Acne/Acneiform
|
6.7%
1/15 • Number of events 1
|
|
Vascular disorders
Flushing
|
6.7%
1/15 • Number of events 1
|
|
Gastrointestinal disorders
Constipation
|
80.0%
12/15 • Number of events 26
|
|
Gastrointestinal disorders
Nausea
|
60.0%
9/15 • Number of events 22
|
|
Gastrointestinal disorders
Anorexia
|
60.0%
9/15 • Number of events 14
|
|
Gastrointestinal disorders
Vomiting
|
46.7%
7/15 • Number of events 10
|
|
Gastrointestinal disorders
Diarrhea
|
26.7%
4/15 • Number of events 5
|
|
Gastrointestinal disorders
Gastritis
|
13.3%
2/15 • Number of events 2
|
|
Nervous system disorders
Taste Alteration (dysgeusia)
|
6.7%
1/15 • Number of events 1
|
|
Metabolism and nutrition disorders
Dehydration
|
6.7%
1/15 • Number of events 2
|
|
Infections and infestations
Infection - Toe
|
6.7%
1/15 • Number of events 1
|
|
Vascular disorders
Edema: Limb
|
26.7%
4/15 • Number of events 6
|
|
Investigations
AST Abnormal
|
93.3%
14/15 • Number of events 34
|
|
Investigations
ALT Abnormal
|
93.3%
14/15 • Number of events 33
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
80.0%
12/15 • Number of events 28
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
73.3%
11/15 • Number of events 27
|
|
Metabolism and nutrition disorders
Hypokalemia
|
66.7%
10/15 • Number of events 31
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
53.3%
8/15 • Number of events 21
|
|
Metabolism and nutrition disorders
Creatinine Abnormal
|
53.3%
8/15 • Number of events 19
|
|
Investigations
Alkaline Phosphatase Abnormal
|
40.0%
6/15 • Number of events 11
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
13.3%
2/15 • Number of events 4
|
|
Investigations
Hypoproteinemia
|
13.3%
2/15 • Number of events 7
|
|
Metabolism and nutrition disorders
Hyponatremia
|
6.7%
1/15 • Number of events 2
|
|
Metabolism and nutrition disorders
Alkalosis (metabolic or respiratory)
|
6.7%
1/15 • Number of events 1
|
|
Metabolism and nutrition disorders
Hyperbilirubinemia
|
6.7%
1/15 • Number of events 1
|
|
Metabolism and nutrition disorders
Chloride High
|
6.7%
1/15 • Number of events 5
|
|
Musculoskeletal and connective tissue disorders
Muscle Weakness
|
6.7%
1/15 • Number of events 2
|
|
Metabolism and nutrition disorders
Leg Cramps
|
6.7%
1/15 • Number of events 1
|
|
Nervous system disorders
Dizziness
|
26.7%
4/15 • Number of events 5
|
|
Nervous system disorders
Neuropathy: Sensory
|
26.7%
4/15 • Number of events 4
|
|
Psychiatric disorders
Mood Alteration
|
20.0%
3/15 • Number of events 3
|
|
Psychiatric disorders
Confusion
|
13.3%
2/15 • Number of events 2
|
|
Nervous system disorders
Ataxia (incoordination)
|
6.7%
1/15 • Number of events 1
|
|
Nervous system disorders
Neuropathy: Motor
|
6.7%
1/15 • Number of events 4
|
|
Eye disorders
Loss of Acuity Related to Illness
|
6.7%
1/15 • Number of events 1
|
|
Eye disorders
Vitreous Detachment
|
6.7%
1/15 • Number of events 1
|
|
Eye disorders
Vision Blurred - Vision
|
6.7%
1/15 • Number of events 1
|
|
Eye disorders
Watery Eye
|
6.7%
1/15 • Number of events 1
|
|
Nervous system disorders
Headache
|
66.7%
10/15 • Number of events 18
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
40.0%
6/15 • Number of events 8
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
6.7%
1/15 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Pain - Chest Wall
|
26.7%
4/15 • Number of events 4
|
|
Musculoskeletal and connective tissue disorders
Pain - Back
|
20.0%
3/15 • Number of events 7
|
|
Musculoskeletal and connective tissue disorders
Pain - Muscle
|
20.0%
3/15 • Number of events 3
|
|
Musculoskeletal and connective tissue disorders
Pain - Bone
|
13.3%
2/15 • Number of events 3
|
|
Gastrointestinal disorders
Abdomen NOS
|
13.3%
2/15 • Number of events 3
|
|
Musculoskeletal and connective tissue disorders
Extremity
|
6.7%
1/15 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Pain - Arm
|
6.7%
1/15 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Pain - Musculoskeletal - Extremity
|
6.7%
1/15 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Pain - Rib
|
6.7%
1/15 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Throat/Pharynx/Larynx
|
6.7%
1/15 • Number of events 1
|
|
General disorders
Pain - Tightness in Shoulders Secondary to Benadryl IV
|
6.7%
1/15 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea (Shortness of Breath)
|
60.0%
9/15 • Number of events 11
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
53.3%
8/15 • Number of events 12
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis
|
13.3%
2/15 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
Pleural Effusion (non-malignant)
|
6.7%
1/15 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Fibrosis (radiologic changes)
|
6.7%
1/15 • Number of events 1
|
|
General disorders
Flu-Like Syndrome
|
33.3%
5/15 • Number of events 10
|
|
Vascular disorders
Acute Vascular Leak Syndrome
|
66.7%
10/15 • Number of events 19
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place