Trial Outcomes & Findings for Aurora A Kinase Inhibitor MLN8237 in Treating Patients With Unresectable Stage III-IV Melanoma (NCT NCT01316692)
NCT ID: NCT01316692
Last Updated: 2016-05-30
Results Overview
If 2 or more of 23 pts show CR/PR in stage 1, then an additional 33 pts will be enrolled in stage 2. If 6 or more of the total 56 pts show CR/PR at 18 weeks, then further clinical trials will be warranted. Per Response Evaluation Criteria in Solid Tumor (RECIST)1.1: Complete response (CR): disappearance of all target lesions. Partial response (PR): \>=30% decrease in sum of LD of target lesion(s), taking as reference baseline sum LD. Patients are categorized according to the best response achieved prior to occurrence of progressive disease, where best response hierarchy is CR\>PR\>SD\>PD.
TERMINATED
PHASE2
12 participants
At 18 weeks
2016-05-30
Participant Flow
Participants on this study were treated at Vanderbilt-Ingram Cancer Center. The study was conducted from October 2011- August 2015
A total of 19 patients consented to participate in this study. Four of 19 patients were screen failures and therefore were not eligible, 3 patients were eligible, but withdrew before treatment.
Participant milestones
| Measure |
MLN8237
Patients receive oral Aurora A kinase inhibitor MLN8237 every 12 hours on days 1-7. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
laboratory biomarker identification and analysis: Correlative studies
biopsy: Correlative studies
immunohistochemistry/tissue microarrays: Correlative studies
TdT-mediated dUTP nick end labeling assay: Correlative studies
mass spectrometry: Correlative studies
|
|---|---|
|
Overall Study
STARTED
|
12
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
12
|
Reasons for withdrawal
| Measure |
MLN8237
Patients receive oral Aurora A kinase inhibitor MLN8237 every 12 hours on days 1-7. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
laboratory biomarker identification and analysis: Correlative studies
biopsy: Correlative studies
immunohistochemistry/tissue microarrays: Correlative studies
TdT-mediated dUTP nick end labeling assay: Correlative studies
mass spectrometry: Correlative studies
|
|---|---|
|
Overall Study
Adverse Event
|
5
|
|
Overall Study
Disease Progression
|
7
|
Baseline Characteristics
Aurora A Kinase Inhibitor MLN8237 in Treating Patients With Unresectable Stage III-IV Melanoma
Baseline characteristics by cohort
| Measure |
MLN8237
n=12 Participants
Patients receive oral Aurora A kinase inhibitor MLN8237 every 12 hours on days 1-7. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
laboratory biomarker identification and analysis: Correlative studies
biopsy: Correlative studies
immunohistochemistry/tissue microarrays: Correlative studies
TdT-mediated dUTP nick end labeling assay: Correlative studies
mass spectrometry: Correlative studies
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
5 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
7 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
12 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 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
|
11 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
|
12 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: At 18 weeksPopulation: All patients with Objective Response, defined as a complete or partial response.
If 2 or more of 23 pts show CR/PR in stage 1, then an additional 33 pts will be enrolled in stage 2. If 6 or more of the total 56 pts show CR/PR at 18 weeks, then further clinical trials will be warranted. Per Response Evaluation Criteria in Solid Tumor (RECIST)1.1: Complete response (CR): disappearance of all target lesions. Partial response (PR): \>=30% decrease in sum of LD of target lesion(s), taking as reference baseline sum LD. Patients are categorized according to the best response achieved prior to occurrence of progressive disease, where best response hierarchy is CR\>PR\>SD\>PD.
Outcome measures
| Measure |
MLN8237
n=12 Participants
Patients receive oral Aurora A kinase inhibitor MLN8237 every 12 hours on days 1-7. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
laboratory biomarker identification and analysis: Correlative studies
biopsy: Correlative studies
immunohistochemistry/tissue microarrays: Correlative studies
TdT-mediated dUTP nick end labeling assay: Correlative studies
mass spectrometry: Correlative studies
|
|---|---|
|
Overall Response Rate
|
0 participants
Interval 0.0 to 0.265
|
SECONDARY outcome
Timeframe: On treatment date to last follow-up, disease progression or death for any reason, up to 5 yearsPopulation: All patients are included in the analysis on intention-to treat basis. Analysis is by Kaplan-Meier method, where death is an event, with censoring for non-expired patients at greater of off-study date or last known alive date.
Progression-free survival (PFS) is defined as the duration in time from start of therapy to last follow-up, disease progression, or death for any reason.measured every 6 weeks for 24 weeks, and then every 12 weeks or to last date known alive or death, determined every 6 months for up to 5 years. For those who are alive and without progression, they are censored at the last date known alive.
Outcome measures
| Measure |
MLN8237
n=12 Participants
Patients receive oral Aurora A kinase inhibitor MLN8237 every 12 hours on days 1-7. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
laboratory biomarker identification and analysis: Correlative studies
biopsy: Correlative studies
immunohistochemistry/tissue microarrays: Correlative studies
TdT-mediated dUTP nick end labeling assay: Correlative studies
mass spectrometry: Correlative studies
|
|---|---|
|
Progression-free Survival
|
111 days
Interval 45.0 to 187.0
|
SECONDARY outcome
Timeframe: On treatment date to last follow-up or death for any reason, up to 5 yearsPopulation: All patients are included in the analysis on intention-to-treat basis. Analysis is by Kaplan-Meier method, where death is an event, with censoring for non-expired patients at greater of off-study date or last known alive date.
Estimated probable duration of life from on-study date to date of death from any cause, using the Kaplan-Meier method with censoring (see analysis population description for additional details) Evaluated every 3 months for 12 months, then every 6 months
Outcome measures
| Measure |
MLN8237
n=12 Participants
Patients receive oral Aurora A kinase inhibitor MLN8237 every 12 hours on days 1-7. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
laboratory biomarker identification and analysis: Correlative studies
biopsy: Correlative studies
immunohistochemistry/tissue microarrays: Correlative studies
TdT-mediated dUTP nick end labeling assay: Correlative studies
mass spectrometry: Correlative studies
|
|---|---|
|
Overall Survival
|
256 days
Interval 136.0 to 419.0
|
SECONDARY outcome
Timeframe: at 18 weeksPopulation: total numbers of adverse events, patients experiencing grade 3 and 4 related to study treatment
Event are graded using National Cancer Institute Common Toxicity Criteria with grade 1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life-threatening/disabling, 5 = death. toxicities measured on day 1 of each 21-day cycle. Treatment continues to disease progression, toxicity, or withdrawal for other reasons.
Outcome measures
| Measure |
MLN8237
n=12 Participants
Patients receive oral Aurora A kinase inhibitor MLN8237 every 12 hours on days 1-7. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
laboratory biomarker identification and analysis: Correlative studies
biopsy: Correlative studies
immunohistochemistry/tissue microarrays: Correlative studies
TdT-mediated dUTP nick end labeling assay: Correlative studies
mass spectrometry: Correlative studies
|
|---|---|
|
Number of Grade 3 and 4 Study-related Toxicities
Grade 3 Toxicities
|
6 toxicities
|
|
Number of Grade 3 and 4 Study-related Toxicities
Grade 4 Toxicities
|
3 toxicities
|
|
Number of Grade 3 and 4 Study-related Toxicities
Grade 5 Toxicities1
|
0 toxicities
|
OTHER_PRE_SPECIFIED outcome
Timeframe: At 24 weeksPopulation: Collected samples of tumors were very limited. It did not allow us to perform the described assays
In stage 1 patients: tumor biopsies are taken before initiation of treatment and on the 8th day of the first cycle of treatment. Tissue will be assayed for mutations that are neither parent-possessed, nor able to be transmitted, in pre- and in post-treatment tissue and the results will be compared and contrasted with patients' objective clinical responses, as determined by RECIST 1.1, after 18 weeks of treatment
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: At 24 weeksPopulation: unable to collected the required number of tumor samples
In stage 2 patients: tumor biopsies are taken before initiation of treatment and on the 8th day of the first cycle of treatment. Post-treatment tumor tissue will be assayed for MLN8237-induced selective Aurora Kinase A inhibition and compared to pre-treatment tumor tissue and the results will be compared and contrasted with patients' objective clinical responses, as determined by RECIST 1.1, after 18 weeks of treatment
Outcome measures
Outcome data not reported
Adverse Events
MLN8237
Serious adverse events
| Measure |
MLN8237
n=12 participants at risk；n=15 participants at risk
Patients receive oral Aurora A kinase inhibitor MLN8237 every 12 hours on days 1-7. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
laboratory biomarker identification and analysis: Correlative studies
biopsy: Correlative studies
immunohistochemistry/tissue microarrays: Correlative studies
TdT-mediated dUTP nick end labeling assay: Correlative studies
mass spectrometry: Correlative studies
|
|---|---|
|
Gastrointestinal disorders
Diarrhea
|
6.7%
1/15 • Number of events 1 • 3 years, 10 months
|
|
Gastrointestinal disorders
Dehydration
|
6.7%
1/15 • Number of events 1 • 3 years, 10 months
|
|
Vascular disorders
Thromboembolic event
|
6.7%
1/15 • Number of events 1 • 3 years, 10 months
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory infection
|
6.7%
1/15 • Number of events 1 • 3 years, 10 months
|
|
Vascular disorders
Bronchial infection
|
6.7%
1/15 • Number of events 1 • 3 years, 10 months
|
|
Blood and lymphatic system disorders
Anemia
|
6.7%
1/15 • Number of events 1 • 3 years, 10 months
|
|
Investigations
Platelet count decreased
|
6.7%
1/15 • Number of events 1 • 3 years, 10 months
|
Other adverse events
| Measure |
MLN8237
n=12 participants at risk；n=15 participants at risk
Patients receive oral Aurora A kinase inhibitor MLN8237 every 12 hours on days 1-7. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
laboratory biomarker identification and analysis: Correlative studies
biopsy: Correlative studies
immunohistochemistry/tissue microarrays: Correlative studies
TdT-mediated dUTP nick end labeling assay: Correlative studies
mass spectrometry: Correlative studies
|
|---|---|
|
Metabolism and nutrition disorders
Hyperglycemia
|
91.7%
11/12 • Number of events 17 • 3 years, 10 months
|
|
Metabolism and nutrition disorders
Anorexia
|
33.3%
4/12 • Number of events 5 • 3 years, 10 months
|
|
Metabolism and nutrition disorders
Hyponatremia
|
25.0%
3/12 • Number of events 3 • 3 years, 10 months
|
|
Metabolism and nutrition disorders
Hypokalemia
|
8.3%
1/12 • Number of events 2 • 3 years, 10 months
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
8.3%
1/12 • Number of events 1 • 3 years, 10 months
|
|
Gastrointestinal disorders
Diarrhea
|
58.3%
7/12 • Number of events 10 • 3 years, 10 months
|
|
Gastrointestinal disorders
Mucositis oral
|
50.0%
6/12 • Number of events 7 • 3 years, 10 months
|
|
Gastrointestinal disorders
Nausea
|
50.0%
6/12 • Number of events 9 • 3 years, 10 months
|
|
Gastrointestinal disorders
Vomiting
|
25.0%
3/12 • Number of events 4 • 3 years, 10 months
|
|
Gastrointestinal disorders
Abdominal pain
|
16.7%
2/12 • Number of events 2 • 3 years, 10 months
|
|
Gastrointestinal disorders
Bloating
|
8.3%
1/12 • Number of events 1 • 3 years, 10 months
|
|
Gastrointestinal disorders
Constipation
|
8.3%
1/12 • Number of events 1 • 3 years, 10 months
|
|
Gastrointestinal disorders
Flatulence
|
8.3%
1/12 • Number of events 1 • 3 years, 10 months
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
8.3%
1/12 • Number of events 1 • 3 years, 10 months
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
83.3%
10/12 • Number of events 12 • 3 years, 10 months
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
8.3%
1/12 • Number of events 1 • 3 years, 10 months
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
8.3%
1/12 • Number of events 1 • 3 years, 10 months
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
8.3%
1/12 • Number of events 1 • 3 years, 10 months
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
8.3%
1/12 • Number of events 1 • 3 years, 10 months
|
|
General disorders
Fatigue
|
66.7%
8/12 • Number of events 11 • 3 years, 10 months
|
|
General disorders
Chills
|
16.7%
2/12 • Number of events 2 • 3 years, 10 months
|
|
General disorders
Pain
|
16.7%
2/12 • Number of events 2 • 3 years, 10 months
|
|
General disorders
Fever
|
8.3%
1/12 • Number of events 1 • 3 years, 10 months
|
|
General disorders
administration site conditions
|
8.3%
1/12 • Number of events 1 • 3 years, 10 months
|
|
Investigations
Lymphocyte count decreased
|
50.0%
6/12 • Number of events 14 • 3 years, 10 months
|
|
Investigations
White blood cell decreased
|
50.0%
6/12 • Number of events 12 • 3 years, 10 months
|
|
Investigations
Neutrophil count decreased
|
41.7%
5/12 • Number of events 9 • 3 years, 10 months
|
|
Investigations
Platelet count decreased
|
25.0%
3/12 • Number of events 9 • 3 years, 10 months
|
|
Investigations
Alkaline phosphatase increased
|
16.7%
2/12 • Number of events 4 • 3 years, 10 months
|
|
Investigations
Aspartate aminotransferase increased
|
16.7%
2/12 • Number of events 2 • 3 years, 10 months
|
|
Investigations
Creatinine increased
|
8.3%
1/12 • Number of events 2 • 3 years, 10 months
|
|
Blood and lymphatic system disorders
Anemia
|
58.3%
7/12 • Number of events 22 • 3 years, 10 months
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
8.3%
1/12 • Number of events 1 • 3 years, 10 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
8.3%
1/12 • Number of events 1 • 3 years, 10 months
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
8.3%
1/12 • Number of events 1 • 3 years, 10 months
|
|
Infections and infestations
Bladder infection
|
8.3%
1/12 • Number of events 1 • 3 years, 10 months
|
|
Infections and infestations
Upper respiratory infection
|
8.3%
1/12 • Number of events 1 • 3 years, 10 months
|
|
Nervous system disorders
Dizziness
|
8.3%
1/12 • Number of events 2 • 3 years, 10 months
|
|
Nervous system disorders
Headache
|
8.3%
1/12 • Number of events 1 • 3 years, 10 months
|
|
Nervous system disorders
Nystagmus
|
8.3%
1/12 • Number of events 1 • 3 years, 10 months
|
|
Nervous system disorders
Tremor
|
8.3%
1/12 • Number of events 1 • 3 years, 10 months
|
|
Nervous system disorders
Syncope
|
8.3%
1/12 • Number of events 1 • 3 years, 10 months
|
|
Renal and urinary disorders
Hematuria
|
16.7%
2/12 • Number of events 5 • 3 years, 10 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
16.7%
2/12 • Number of events 2 • 3 years, 10 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
8.3%
1/12 • Number of events 1 • 3 years, 10 months
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
8.3%
1/12 • Number of events 1 • 3 years, 10 months
|
|
Respiratory, thoracic and mediastinal disorders
Sneezing
|
8.3%
1/12 • Number of events 1 • 3 years, 10 months
|
|
Vascular disorders
Hypotension
|
8.3%
1/12 • Number of events 1 • 3 years, 10 months
|
|
Vascular disorders
Thromboembolic event
|
8.3%
1/12 • Number of events 1 • 3 years, 10 months
|
|
Cardiac disorders
Palpitations
|
8.3%
1/12 • Number of events 1 • 3 years, 10 months
|
|
Psychiatric disorders
Confusion
|
8.3%
1/12 • Number of events 1 • 3 years, 10 months
|
|
Psychiatric disorders
Depression
|
8.3%
1/12 • Number of events 1 • 3 years, 10 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place