Trial Outcomes & Findings for Pevonedistat Alone and in Combination With Chemotherapy in Patients With Mesothelioma (NCT NCT03319537)
NCT ID: NCT03319537
Last Updated: 2024-05-23
Results Overview
The CBR is defined as the proportion of patients CR, PR or SD at 18 weeks based on RECIST criteria.
Recruitment status
TERMINATED
Study phase
PHASE1/PHASE2
Target enrollment
9 participants
Primary outcome timeframe
at 18 weeks post initiation of treatment
Results posted on
2024-05-23
Participant Flow
Participant milestones
| Measure |
Pevonedistat
pevonedistat: Pevonedistat will be administered as an IV infusion at a dose of 50 mg/m2 days 1, 3, and 5 of a 21-day cycle.Treatment will be administered as an outpatient.
|
Pevonedistat in Combination With Pemetrexed and Cisplatin
pevonedistat: Pevonedistat will be administered as an IV infusion at a dose of 50 mg/m2 days 1, 3, and 5 of a 21-day cycle.Treatment will be administered as an outpatient.
Pemetrexed and cisplatin: Pemetrexed, 500 mg/m2 and cisplatin, 75 mg/m2, will be given at fixed doses on day 1 of each cycle.
|
|---|---|---|
|
Overall Study
STARTED
|
9
|
0
|
|
Overall Study
COMPLETED
|
9
|
0
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Pevonedistat Alone and in Combination With Chemotherapy in Patients With Mesothelioma
Baseline characteristics by cohort
| Measure |
Pevonedistat
n=9 Participants
pevonedistat: Pevonedistat will be administered as an IV infusion at a dose of 50 mg/m2 days 1, 3, and 5 of a 21-day cycle.Treatment will be administered as an outpatient.
|
Pevonedistat in Combination With Pemetrexed and Cisplatin
pevonedistat: Pevonedistat will be administered as an IV infusion at a dose of 50 mg/m2 days 1, 3, and 5 of a 21-day cycle.Treatment will be administered as an outpatient.
Pemetrexed and cisplatin: Pemetrexed, 500 mg/m2 and cisplatin, 75 mg/m2, will be given at fixed doses on day 1 of each cycle.
|
Total
n=9 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
62.19 years
n=5 Participants
|
—
|
62.19 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
—
|
1 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
—
|
8 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
—
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
7 Participants
n=5 Participants
|
—
|
7 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
—
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
—
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
—
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
—
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
—
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
9 Participants
n=5 Participants
|
—
|
9 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
—
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
—
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
9 Participants
n=5 Participants
|
—
|
9 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: at 18 weeks post initiation of treatmentPopulation: No participants accrued to pevonedistat in combination with pemetrexed and cisplatin cohort
The CBR is defined as the proportion of patients CR, PR or SD at 18 weeks based on RECIST criteria.
Outcome measures
| Measure |
Pevonedistat
n=9 Participants
pevonedistat: Pevonedistat will be administered as an IV infusion at a dose of 50 mg/m2 days 1, 3, and 5 of a 21-day cycle.Treatment will be administered as an outpatient.
|
Pevonedistat in Combination With Pemetrexed and Cisplatin
pevonedistat: Pevonedistat will be administered as an IV infusion at a dose of 50 mg/m2 days 1, 3, and 5 of a 21-day cycle.Treatment will be administered as an outpatient.
Pemetrexed and cisplatin: Pemetrexed, 500 mg/m2 and cisplatin, 75 mg/m2, will be given at fixed doses on day 1 of each cycle.
|
|---|---|---|
|
Number of Patients Who Have a Clinical Benefit Rate (CBR) (Cohort 1)
Participants who have a Clinical Benefit Rate/CBR
|
2 Participants
|
—
|
|
Number of Patients Who Have a Clinical Benefit Rate (CBR) (Cohort 1)
Participants without a Clinical Benefit Rate/CBR
|
7 Participants
|
—
|
PRIMARY outcome
Timeframe: 3 yearPopulation: N/A - Data were not collected
If none of the initial cohort of 3 has a dose-limited toxicity the dose level will be escalated. If one has a DLT that dose level will be expanded with 3 more patients. Dose escalation will stop if ≥2 DLTs are seen at a dose level. The MTD is defined as the highest dose level at which no more than 1 of the 6 patients at that level has a DLT. If no patient in the 3-patient cohort has a DLT and the dose level is under final consideration of the MTD, an additional three patients will be treated at that level for confirmation.
Outcome measures
Outcome data not reported
Adverse Events
Pevonedistat
Serious events: 3 serious events
Other events: 7 other events
Deaths: 8 deaths
Pevonedistat in Combination With Pemetrexed and Cisplatin
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Pevonedistat
n=9 participants at risk
pevonedistat: Pevonedistat will be administered as an IV infusion at a dose of 50 mg/m2 days 1, 3, and 5 of a 21-day cycle.Treatment will be administered as an outpatient.
|
Pevonedistat in Combination With Pemetrexed and Cisplatin
pevonedistat: Pevonedistat will be administered as an IV infusion at a dose of 50 mg/m2 days 1, 3, and 5 of a 21-day cycle.Treatment will be administered as an outpatient.
Pemetrexed and cisplatin: Pemetrexed, 500 mg/m2 and cisplatin, 75 mg/m2, will be given at fixed doses on day 1 of each cycle.
|
|---|---|---|
|
Gastrointestinal disorders
Upper Gastrointestinal Hemorrhage
|
11.1%
1/9 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
—
0/0 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
11.1%
1/9 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
—
0/0 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms ben/mal/unk (inc cyst/polyp
|
11.1%
1/9 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
—
0/0 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
|
General disorders
Death NOS
|
11.1%
1/9 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
—
0/0 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
Other adverse events
| Measure |
Pevonedistat
n=9 participants at risk
pevonedistat: Pevonedistat will be administered as an IV infusion at a dose of 50 mg/m2 days 1, 3, and 5 of a 21-day cycle.Treatment will be administered as an outpatient.
|
Pevonedistat in Combination With Pemetrexed and Cisplatin
pevonedistat: Pevonedistat will be administered as an IV infusion at a dose of 50 mg/m2 days 1, 3, and 5 of a 21-day cycle.Treatment will be administered as an outpatient.
Pemetrexed and cisplatin: Pemetrexed, 500 mg/m2 and cisplatin, 75 mg/m2, will be given at fixed doses on day 1 of each cycle.
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal Pain
|
22.2%
2/9 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
—
0/0 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
|
Investigations
Alanine aminotransferase increased
|
11.1%
1/9 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
—
0/0 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
|
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis
|
11.1%
1/9 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
—
0/0 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
|
Metabolism and nutrition disorders
Anorexia
|
22.2%
2/9 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
—
0/0 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
|
Psychiatric disorders
Anxiety
|
33.3%
3/9 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
—
0/0 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
|
Investigations
Aspartate aminotransferase increased
|
11.1%
1/9 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
—
0/0 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
33.3%
3/9 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
—
0/0 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
|
Musculoskeletal and connective tissue disorders
Chest wall pain
|
11.1%
1/9 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
—
0/0 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
|
General disorders
Chills
|
11.1%
1/9 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
—
0/0 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
|
Gastrointestinal disorders
Constipation
|
44.4%
4/9 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
—
0/0 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
33.3%
3/9 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
—
0/0 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
|
Metabolism and nutrition disorders
Decreased appetite
|
11.1%
1/9 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
—
0/0 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
|
Metabolism and nutrition disorders
Dehydration
|
11.1%
1/9 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
—
0/0 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
|
Gastrointestinal disorders
Diarrhea
|
22.2%
2/9 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
—
0/0 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
|
Nervous system disorders
Dizziness
|
22.2%
2/9 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
—
0/0 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
|
Eye disorders
Dry eye
|
11.1%
1/9 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
—
0/0 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
33.3%
3/9 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
—
0/0 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
|
General disorders
Edema limbs
|
11.1%
1/9 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
—
0/0 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
|
General disorders
Fatigue
|
44.4%
4/9 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
—
0/0 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
|
General disorders
Fever
|
11.1%
1/9 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
—
0/0 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
|
Gastrointestinal disorders
Flatulence
|
11.1%
1/9 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
—
0/0 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
11.1%
1/9 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
—
0/0 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
|
Nervous system disorders
Headache
|
11.1%
1/9 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
—
0/0 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
|
Vascular disorders
Hypertension
|
11.1%
1/9 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
—
0/0 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
|
Psychiatric disorders
Insomnia
|
11.1%
1/9 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
—
0/0 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
11.1%
1/9 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
—
0/0 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
11.1%
1/9 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
—
0/0 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
|
Gastrointestinal disorders
Nausea
|
33.3%
3/9 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
—
0/0 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
|
General disorders
Pain
|
22.2%
2/9 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
—
0/0 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
|
Respiratory, thoracic and mediastinal disorders
Productive Cough
|
22.2%
2/9 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
—
0/0 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
22.2%
2/9 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
—
0/0 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
|
Cardiac disorders
Sinus tachycardia
|
11.1%
1/9 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
—
0/0 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
|
Respiratory, thoracic and mediastinal disorders
Sore throat
|
11.1%
1/9 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
—
0/0 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
|
Infections and infestations
Upper respiratory infection
|
11.1%
1/9 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
—
0/0 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
|
Gastrointestinal disorders
Vomiting
|
11.1%
1/9 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
—
0/0 • 1 year
No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort
|
Additional Information
Dr. Marjorie Zauderer, MD
Memorial Sloan Kettering Cancer Center
Phone: 646-608-3790
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place