Trial Outcomes & Findings for A Trial of ASP7487 (OSI-906) in Combination With Bortezomib for the Treatment of Relapsed Multiple Myeloma (NCT NCT01672736)
NCT ID: NCT01672736
Last Updated: 2018-09-13
Results Overview
* Phase 1: To determine the maximum tolerated dose (MTD) of ASP7487 (OSI-906) administered in combination with the recommended dose and schedule of bortezomib and dexamethasone; * Phase 2: To evaluate the antitumor activity of ASP7487 (OSI-906) in combination with bortezomib and dexamethasone at the MTD established from the Phase 1 component.
Recruitment status
TERMINATED
Study phase
PHASE1/PHASE2
Target enrollment
19 participants
Primary outcome timeframe
45 months
Results posted on
2018-09-13
Participant Flow
Subject enrollment under this IND was stopped prematurely due to the drug manufacturer's decision to terminate the development of the study drug, Linsitinib (letter dated 1 November 2015). Therefore, the study did not proceed to Phase II portion of the study protocol. The available study drug supply at the study sites expired on 31 May 2016.
Participant milestones
| Measure |
ASP7487, Velcade, Dexamethasone
ASP7487 administered orally 75, 100 and 150 mg) BID continuously for each cycle. Bortezomib administered at 1.3 mg/m2 twice weekly for the first 8 21 day cycles and once weekly beyond cycle 9 for 35 day cycles. Dexamethasone is administered on bortezomib administration days at 20 mg
ASP7487, Velcade, Dexamethasone: ASP7487- Oral (75, 100, 150 mg)BID Bortezomib- 1.3 mg/m2 IV on days 1, 4, 8, 15 of each 21 day cycle up to cycle 8 and days 1, 5, 15, 22 of each 35 day cycle beyond cycle 9 Dexamethasone- 20 mg on the day of Bortezomib administration
|
|---|---|
|
Overall Study
STARTED
|
19
|
|
Overall Study
COMPLETED
|
16
|
|
Overall Study
NOT COMPLETED
|
3
|
Reasons for withdrawal
| Measure |
ASP7487, Velcade, Dexamethasone
ASP7487 administered orally 75, 100 and 150 mg) BID continuously for each cycle. Bortezomib administered at 1.3 mg/m2 twice weekly for the first 8 21 day cycles and once weekly beyond cycle 9 for 35 day cycles. Dexamethasone is administered on bortezomib administration days at 20 mg
ASP7487, Velcade, Dexamethasone: ASP7487- Oral (75, 100, 150 mg)BID Bortezomib- 1.3 mg/m2 IV on days 1, 4, 8, 15 of each 21 day cycle up to cycle 8 and days 1, 5, 15, 22 of each 35 day cycle beyond cycle 9 Dexamethasone- 20 mg on the day of Bortezomib administration
|
|---|---|
|
Overall Study
Available drug expired on 31 May 16
|
3
|
Baseline Characteristics
A Trial of ASP7487 (OSI-906) in Combination With Bortezomib for the Treatment of Relapsed Multiple Myeloma
Baseline characteristics by cohort
| Measure |
ASP7487, Velcade, Dexamethasone
n=19 Participants
ASP7487 administered orally 75, 100 and 150 mg) BID continuously for each cycle. Bortezomib administered at 1.3 mg/m2 twice weekly for the first 8 21 day cycles and once weekly beyond cycle 9 for 35 day cycles. Dexamethasone is administered on bortezomib administration days at 20 mg
ASP7487, Velcade, Dexamethasone: ASP7487- Oral (75, 100, 150 mg)BID Bortezomib- 1.3 mg/m2 IV on days 1, 4, 8, 15 of each 21 day cycle up to cycle 8 and days 1, 5, 15, 22 of each 35 day cycle beyond cycle 9 Dexamethasone- 20 mg on the day of Bortezomib administration
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
12 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
7 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
17 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
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
15 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
Canada
|
18 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
1 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 45 months* Phase 1: To determine the maximum tolerated dose (MTD) of ASP7487 (OSI-906) administered in combination with the recommended dose and schedule of bortezomib and dexamethasone; * Phase 2: To evaluate the antitumor activity of ASP7487 (OSI-906) in combination with bortezomib and dexamethasone at the MTD established from the Phase 1 component.
Outcome measures
| Measure |
ASP7487, Velcade, Dexamethasone
n=19 Participants
ASP7487 administered orally 75, 100 and 150 mg) BID continuously for each cycle. Bortezomib administered at 1.3 mg/m2 twice weekly for the first 8 21 day cycles and once weekly beyond cycle 9 for 35 day cycles. Dexamethasone is administered on bortezomib administration days at 20 mg
ASP7487, Velcade, Dexamethasone: ASP7487- Oral (75, 100, 150 mg)BID Bortezomib- 1.3 mg/m2 IV on days 1, 4, 8, 15 of each 21 day cycle up to cycle 8 and days 1, 5, 15, 22 of each 35 day cycle beyond cycle 9 Dexamethasone- 20 mg on the day of Bortezomib administration
|
|---|---|
|
Maximum Tolerated Dose of the Combination of ASP7487 (OSI-906) With Velcade and Dexamethasone
Linsitinib starting dose in milligrams
|
75 milligrams
|
|
Maximum Tolerated Dose of the Combination of ASP7487 (OSI-906) With Velcade and Dexamethasone
Linsitinib maximum dose in milligrams
|
150 milligrams
|
Adverse Events
ASP7487, Velcade, Dexamethasone
Serious events: 8 serious events
Other events: 19 other events
Deaths: 2 deaths
Serious adverse events
| Measure |
ASP7487, Velcade, Dexamethasone
n=19 participants at risk
ASP7487 administered orally 75, 100 and 150 mg) BID continuously for each cycle. Bortezomib administered at 1.3 mg/m2 twice weekly for the first 8 21 day cycles and once weekly beyond cycle 9 for 35 day cycles. Dexamethasone is administered on bortezomib administration days at 20 mg
ASP7487, Velcade, Dexamethasone: ASP7487- Oral (75, 100, 150 mg)BID Bortezomib- 1.3 mg/m2 IV on days 1, 4, 8, 15 of each 21 day cycle up to cycle 8 and days 1, 5, 15, 22 of each 35 day cycle beyond cycle 9 Dexamethasone- 20 mg on the day of Bortezomib administration
|
|---|---|
|
Investigations
Alanine Aminitransferase Increased
|
5.3%
1/19 • Number of events 1 • 4 years and 10 months. This period includes the time period from study activation to the final data analysis, the results of which are presented here.The adverse event data was collected from study activation on 3 Oct 2012 up to 22 Aug 2017.
Adverse Events were graded in accordance with CTCAE v4.03
|
|
Investigations
Asparate Aminotransferase increased
|
5.3%
1/19 • Number of events 1 • 4 years and 10 months. This period includes the time period from study activation to the final data analysis, the results of which are presented here.The adverse event data was collected from study activation on 3 Oct 2012 up to 22 Aug 2017.
Adverse Events were graded in accordance with CTCAE v4.03
|
|
Nervous system disorders
Delirium
|
5.3%
1/19 • Number of events 1 • 4 years and 10 months. This period includes the time period from study activation to the final data analysis, the results of which are presented here.The adverse event data was collected from study activation on 3 Oct 2012 up to 22 Aug 2017.
Adverse Events were graded in accordance with CTCAE v4.03
|
|
Infections and infestations
Lung infection
|
10.5%
2/19 • Number of events 2 • 4 years and 10 months. This period includes the time period from study activation to the final data analysis, the results of which are presented here.The adverse event data was collected from study activation on 3 Oct 2012 up to 22 Aug 2017.
Adverse Events were graded in accordance with CTCAE v4.03
|
|
General disorders
Death due to multiple myeloma
|
5.3%
1/19 • Number of events 1 • 4 years and 10 months. This period includes the time period from study activation to the final data analysis, the results of which are presented here.The adverse event data was collected from study activation on 3 Oct 2012 up to 22 Aug 2017.
Adverse Events were graded in accordance with CTCAE v4.03
|
|
Cardiac disorders
Cardiac arrest
|
5.3%
1/19 • Number of events 1 • 4 years and 10 months. This period includes the time period from study activation to the final data analysis, the results of which are presented here.The adverse event data was collected from study activation on 3 Oct 2012 up to 22 Aug 2017.
Adverse Events were graded in accordance with CTCAE v4.03
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
5.3%
1/19 • Number of events 1 • 4 years and 10 months. This period includes the time period from study activation to the final data analysis, the results of which are presented here.The adverse event data was collected from study activation on 3 Oct 2012 up to 22 Aug 2017.
Adverse Events were graded in accordance with CTCAE v4.03
|
|
General disorders
fever
|
10.5%
2/19 • Number of events 2 • 4 years and 10 months. This period includes the time period from study activation to the final data analysis, the results of which are presented here.The adverse event data was collected from study activation on 3 Oct 2012 up to 22 Aug 2017.
Adverse Events were graded in accordance with CTCAE v4.03
|
|
Respiratory, thoracic and mediastinal disorders
dyspnea
|
5.3%
1/19 • Number of events 1 • 4 years and 10 months. This period includes the time period from study activation to the final data analysis, the results of which are presented here.The adverse event data was collected from study activation on 3 Oct 2012 up to 22 Aug 2017.
Adverse Events were graded in accordance with CTCAE v4.03
|
Other adverse events
| Measure |
ASP7487, Velcade, Dexamethasone
n=19 participants at risk
ASP7487 administered orally 75, 100 and 150 mg) BID continuously for each cycle. Bortezomib administered at 1.3 mg/m2 twice weekly for the first 8 21 day cycles and once weekly beyond cycle 9 for 35 day cycles. Dexamethasone is administered on bortezomib administration days at 20 mg
ASP7487, Velcade, Dexamethasone: ASP7487- Oral (75, 100, 150 mg)BID Bortezomib- 1.3 mg/m2 IV on days 1, 4, 8, 15 of each 21 day cycle up to cycle 8 and days 1, 5, 15, 22 of each 35 day cycle beyond cycle 9 Dexamethasone- 20 mg on the day of Bortezomib administration
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
36.8%
7/19 • 4 years and 10 months. This period includes the time period from study activation to the final data analysis, the results of which are presented here.The adverse event data was collected from study activation on 3 Oct 2012 up to 22 Aug 2017.
Adverse Events were graded in accordance with CTCAE v4.03
|
|
Gastrointestinal disorders
Diarrhea
|
36.8%
7/19 • 4 years and 10 months. This period includes the time period from study activation to the final data analysis, the results of which are presented here.The adverse event data was collected from study activation on 3 Oct 2012 up to 22 Aug 2017.
Adverse Events were graded in accordance with CTCAE v4.03
|
|
Gastrointestinal disorders
Nausea
|
42.1%
8/19 • 4 years and 10 months. This period includes the time period from study activation to the final data analysis, the results of which are presented here.The adverse event data was collected from study activation on 3 Oct 2012 up to 22 Aug 2017.
Adverse Events were graded in accordance with CTCAE v4.03
|
|
General disorders
Fatigue
|
36.8%
7/19 • 4 years and 10 months. This period includes the time period from study activation to the final data analysis, the results of which are presented here.The adverse event data was collected from study activation on 3 Oct 2012 up to 22 Aug 2017.
Adverse Events were graded in accordance with CTCAE v4.03
|
|
Infections and infestations
Pneumonia/influenza
|
21.1%
4/19 • 4 years and 10 months. This period includes the time period from study activation to the final data analysis, the results of which are presented here.The adverse event data was collected from study activation on 3 Oct 2012 up to 22 Aug 2017.
Adverse Events were graded in accordance with CTCAE v4.03
|
|
Investigations
Creatinine Increased
|
42.1%
8/19 • 4 years and 10 months. This period includes the time period from study activation to the final data analysis, the results of which are presented here.The adverse event data was collected from study activation on 3 Oct 2012 up to 22 Aug 2017.
Adverse Events were graded in accordance with CTCAE v4.03
|
|
Investigations
Platelet count decreased
|
68.4%
13/19 • 4 years and 10 months. This period includes the time period from study activation to the final data analysis, the results of which are presented here.The adverse event data was collected from study activation on 3 Oct 2012 up to 22 Aug 2017.
Adverse Events were graded in accordance with CTCAE v4.03
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
15.8%
3/19 • 4 years and 10 months. This period includes the time period from study activation to the final data analysis, the results of which are presented here.The adverse event data was collected from study activation on 3 Oct 2012 up to 22 Aug 2017.
Adverse Events were graded in accordance with CTCAE v4.03
|
|
Nervous system disorders
Headache
|
21.1%
4/19 • 4 years and 10 months. This period includes the time period from study activation to the final data analysis, the results of which are presented here.The adverse event data was collected from study activation on 3 Oct 2012 up to 22 Aug 2017.
Adverse Events were graded in accordance with CTCAE v4.03
|
|
Nervous system disorders
Neuropathy
|
31.6%
6/19 • 4 years and 10 months. This period includes the time period from study activation to the final data analysis, the results of which are presented here.The adverse event data was collected from study activation on 3 Oct 2012 up to 22 Aug 2017.
Adverse Events were graded in accordance with CTCAE v4.03
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
31.6%
6/19 • 4 years and 10 months. This period includes the time period from study activation to the final data analysis, the results of which are presented here.The adverse event data was collected from study activation on 3 Oct 2012 up to 22 Aug 2017.
Adverse Events were graded in accordance with CTCAE v4.03
|
Additional Information
Dr. Suzanne Trudel
University Health Network - Princess Margaret Cancer Centre
Phone: 416-946-4501
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60