Trial Outcomes & Findings for SARC023: Ganetespib and Sirolimus in Patients With MPNST (Malignant Peripheral Nerve Sheath Tumors) (NCT NCT02008877)
NCT ID: NCT02008877
Last Updated: 2019-05-15
Results Overview
To assess the safety, tolerability, and maximum tolerated/ recommended dose of ganetespib when administered in combination with sirolimus in patients with refractory sarcomas or unresectable or metastatic sporadic or neurofibromatosis type 1 (NF1) associated MPNST. Toxicities observed during the first cycle will be used to define the MTD/Recommended dose. Toxicity will be graded using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. DLT will be defined as any of the following events that are possibly, probably, or definitely attributable to ganetespib or sirolimus. The DLT observation period for the purposes of dose escalation will be the first cycle of therapy.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
20 participants
Primary outcome timeframe
Toxicities will be evaluated over the first treatment cycle (each cycle=28 days)
Results posted on
2019-05-15
Participant Flow
Participant milestones
| Measure |
Phase 1 Dose 1
For each 28-day cycle, subjects took doses of both ganetespib + sirolimus:
ganetespib: 150 mg/m² IV on days 1, 8, and 15 intravenously over 1 hour
Sirolimus: 4mg taken orally once daily on a continuous dosing schedule; Loading dose 12 mg on cycle 1 day 1 only.
|
Phase 1 Dose 2
For each 28-day cycle, subjects took doses of both ganetespib + sirolimus:
ganetespib: 200 mg/m² IV on days 1, 8, and 15 intravenously over 1 hour
Sirolimus: 4mg taken orally once daily on a continuous dosing schedule; Loading dose 12 mg on cycle 1 day 1 only.
|
Phase 2
For each 28-day cycle, subjects took doses of both ganetespib + sirolimus:
ganetespib: 200 mg/m² IV on days 1, 8, and 15 intravenously over 1 hour
Sirolimus: 4mg taken orally once daily on a continuous dosing schedule; Loading dose 12 mg on cycle 1 day 1 only.
|
|---|---|---|---|
|
Overall Study
STARTED
|
3
|
7
|
10
|
|
Overall Study
COMPLETED
|
3
|
6
|
10
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
0
|
Reasons for withdrawal
| Measure |
Phase 1 Dose 1
For each 28-day cycle, subjects took doses of both ganetespib + sirolimus:
ganetespib: 150 mg/m² IV on days 1, 8, and 15 intravenously over 1 hour
Sirolimus: 4mg taken orally once daily on a continuous dosing schedule; Loading dose 12 mg on cycle 1 day 1 only.
|
Phase 1 Dose 2
For each 28-day cycle, subjects took doses of both ganetespib + sirolimus:
ganetespib: 200 mg/m² IV on days 1, 8, and 15 intravenously over 1 hour
Sirolimus: 4mg taken orally once daily on a continuous dosing schedule; Loading dose 12 mg on cycle 1 day 1 only.
|
Phase 2
For each 28-day cycle, subjects took doses of both ganetespib + sirolimus:
ganetespib: 200 mg/m² IV on days 1, 8, and 15 intravenously over 1 hour
Sirolimus: 4mg taken orally once daily on a continuous dosing schedule; Loading dose 12 mg on cycle 1 day 1 only.
|
|---|---|---|---|
|
Overall Study
Inevaluable
|
0
|
1
|
0
|
Baseline Characteristics
10 patients were enrolled in Phase 1 and 10 patients were enrolled in Phase 2 of the study. Overall number of patients enrolled was 20.
Baseline characteristics by cohort
| Measure |
Ganetespib / Sirolimus
n=20 Participants
28-day cycles of ganetespib + sirolimus
ganetespib: 200 mg/m² IV on days 1, 8, and 15 intravenously over 1 hour
Sirolimus: 2mg taken orally once daily on a continuous dosing schedule; Loading dose 12 mg on cycle 1 day 1 only.
|
|---|---|
|
Age, Continuous
Phase I
|
26 years
n=10 Participants • 10 patients were enrolled in Phase 1 and 10 patients were enrolled in Phase 2 of the study. Overall number of patients enrolled was 20.
|
|
Age, Continuous
Phase 2
|
38 years
n=10 Participants • 10 patients were enrolled in Phase 1 and 10 patients were enrolled in Phase 2 of the study. Overall number of patients enrolled was 20.
|
|
Sex: Female, Male
Phase I · Female
|
2 Participants
n=10 Participants • 10 patients were enrolled in Phase 1 and 10 patients were enrolled in Phase 2 of the study. Overall number of patients enrolled was 20.
|
|
Sex: Female, Male
Phase I · Male
|
8 Participants
n=10 Participants • 10 patients were enrolled in Phase 1 and 10 patients were enrolled in Phase 2 of the study. Overall number of patients enrolled was 20.
|
|
Sex: Female, Male
Phase 2 · Female
|
4 Participants
n=10 Participants • 10 patients were enrolled in Phase 1 and 10 patients were enrolled in Phase 2 of the study. Overall number of patients enrolled was 20.
|
|
Sex: Female, Male
Phase 2 · Male
|
6 Participants
n=10 Participants • 10 patients were enrolled in Phase 1 and 10 patients were enrolled in Phase 2 of the study. Overall number of patients enrolled was 20.
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
4 Participants
n=20 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
16 Participants
n=20 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=20 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=20 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=20 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=20 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=20 Participants
|
|
Race (NIH/OMB)
White
|
14 Participants
n=20 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=20 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=20 Participants
|
|
Sarcoma subtype
Phase I · Alveolar soft part sarcoma
|
1 Participants
n=10 Participants • 10 patients were enrolled in Phase 1 and 10 patients were enrolled in Phase 2 of the study. Overall number of patients enrolled was 20.
|
|
Sarcoma subtype
Phase I · Ewing sarcoma
|
1 Participants
n=10 Participants • 10 patients were enrolled in Phase 1 and 10 patients were enrolled in Phase 2 of the study. Overall number of patients enrolled was 20.
|
|
Sarcoma subtype
Phase I · Leiomyosarcoma
|
2 Participants
n=10 Participants • 10 patients were enrolled in Phase 1 and 10 patients were enrolled in Phase 2 of the study. Overall number of patients enrolled was 20.
|
|
Sarcoma subtype
Phase I · Liposarcoma
|
3 Participants
n=10 Participants • 10 patients were enrolled in Phase 1 and 10 patients were enrolled in Phase 2 of the study. Overall number of patients enrolled was 20.
|
|
Sarcoma subtype
Phase I · MPNST NF1 Associated
|
3 Participants
n=10 Participants • 10 patients were enrolled in Phase 1 and 10 patients were enrolled in Phase 2 of the study. Overall number of patients enrolled was 20.
|
|
Sarcoma subtype
Phase I · MPNST Sporadic
|
0 Participants
n=10 Participants • 10 patients were enrolled in Phase 1 and 10 patients were enrolled in Phase 2 of the study. Overall number of patients enrolled was 20.
|
|
Sarcoma subtype
Phase 2 · Alveolar soft part sarcoma
|
0 Participants
n=10 Participants • 10 patients were enrolled in Phase 1 and 10 patients were enrolled in Phase 2 of the study. Overall number of patients enrolled was 20.
|
|
Sarcoma subtype
Phase 2 · Ewing sarcoma
|
0 Participants
n=10 Participants • 10 patients were enrolled in Phase 1 and 10 patients were enrolled in Phase 2 of the study. Overall number of patients enrolled was 20.
|
|
Sarcoma subtype
Phase 2 · Leiomyosarcoma
|
0 Participants
n=10 Participants • 10 patients were enrolled in Phase 1 and 10 patients were enrolled in Phase 2 of the study. Overall number of patients enrolled was 20.
|
|
Sarcoma subtype
Phase 2 · Liposarcoma
|
0 Participants
n=10 Participants • 10 patients were enrolled in Phase 1 and 10 patients were enrolled in Phase 2 of the study. Overall number of patients enrolled was 20.
|
|
Sarcoma subtype
Phase 2 · MPNST NF1 Associated
|
5 Participants
n=10 Participants • 10 patients were enrolled in Phase 1 and 10 patients were enrolled in Phase 2 of the study. Overall number of patients enrolled was 20.
|
|
Sarcoma subtype
Phase 2 · MPNST Sporadic
|
5 Participants
n=10 Participants • 10 patients were enrolled in Phase 1 and 10 patients were enrolled in Phase 2 of the study. Overall number of patients enrolled was 20.
|
|
Tumor location at diagnosis
Phase I · Abdomen
|
1 Participants
n=10 Participants • 10 patients were enrolled in Phase 1 and 10 patients were enrolled in Phase 2 of the study. Overall number of patients enrolled was 20.
|
|
Tumor location at diagnosis
Phase I · Extremity
|
1 Participants
n=10 Participants • 10 patients were enrolled in Phase 1 and 10 patients were enrolled in Phase 2 of the study. Overall number of patients enrolled was 20.
|
|
Tumor location at diagnosis
Phase I · Head
|
1 Participants
n=10 Participants • 10 patients were enrolled in Phase 1 and 10 patients were enrolled in Phase 2 of the study. Overall number of patients enrolled was 20.
|
|
Tumor location at diagnosis
Phase I · Lung
|
0 Participants
n=10 Participants • 10 patients were enrolled in Phase 1 and 10 patients were enrolled in Phase 2 of the study. Overall number of patients enrolled was 20.
|
|
Tumor location at diagnosis
Phase I · Mediastinum
|
1 Participants
n=10 Participants • 10 patients were enrolled in Phase 1 and 10 patients were enrolled in Phase 2 of the study. Overall number of patients enrolled was 20.
|
|
Tumor location at diagnosis
Phase I · Peritoneum
|
1 Participants
n=10 Participants • 10 patients were enrolled in Phase 1 and 10 patients were enrolled in Phase 2 of the study. Overall number of patients enrolled was 20.
|
|
Tumor location at diagnosis
Phase I · Skin
|
1 Participants
n=10 Participants • 10 patients were enrolled in Phase 1 and 10 patients were enrolled in Phase 2 of the study. Overall number of patients enrolled was 20.
|
|
Tumor location at diagnosis
Phase I · Spine
|
1 Participants
n=10 Participants • 10 patients were enrolled in Phase 1 and 10 patients were enrolled in Phase 2 of the study. Overall number of patients enrolled was 20.
|
|
Tumor location at diagnosis
Phase I · Other
|
3 Participants
n=10 Participants • 10 patients were enrolled in Phase 1 and 10 patients were enrolled in Phase 2 of the study. Overall number of patients enrolled was 20.
|
|
Tumor location at diagnosis
Phase 2 · Abdomen
|
1 Participants
n=10 Participants • 10 patients were enrolled in Phase 1 and 10 patients were enrolled in Phase 2 of the study. Overall number of patients enrolled was 20.
|
|
Tumor location at diagnosis
Phase 2 · Extremity
|
4 Participants
n=10 Participants • 10 patients were enrolled in Phase 1 and 10 patients were enrolled in Phase 2 of the study. Overall number of patients enrolled was 20.
|
|
Tumor location at diagnosis
Phase 2 · Head
|
0 Participants
n=10 Participants • 10 patients were enrolled in Phase 1 and 10 patients were enrolled in Phase 2 of the study. Overall number of patients enrolled was 20.
|
|
Tumor location at diagnosis
Phase 2 · Lung
|
1 Participants
n=10 Participants • 10 patients were enrolled in Phase 1 and 10 patients were enrolled in Phase 2 of the study. Overall number of patients enrolled was 20.
|
|
Tumor location at diagnosis
Phase 2 · Mediastinum
|
0 Participants
n=10 Participants • 10 patients were enrolled in Phase 1 and 10 patients were enrolled in Phase 2 of the study. Overall number of patients enrolled was 20.
|
|
Tumor location at diagnosis
Phase 2 · Peritoneum
|
0 Participants
n=10 Participants • 10 patients were enrolled in Phase 1 and 10 patients were enrolled in Phase 2 of the study. Overall number of patients enrolled was 20.
|
|
Tumor location at diagnosis
Phase 2 · Skin
|
0 Participants
n=10 Participants • 10 patients were enrolled in Phase 1 and 10 patients were enrolled in Phase 2 of the study. Overall number of patients enrolled was 20.
|
|
Tumor location at diagnosis
Phase 2 · Spine
|
2 Participants
n=10 Participants • 10 patients were enrolled in Phase 1 and 10 patients were enrolled in Phase 2 of the study. Overall number of patients enrolled was 20.
|
|
Tumor location at diagnosis
Phase 2 · Other
|
2 Participants
n=10 Participants • 10 patients were enrolled in Phase 1 and 10 patients were enrolled in Phase 2 of the study. Overall number of patients enrolled was 20.
|
|
History of metastatic disease
Phase 1
|
9 Participants
n=10 Participants • 10 patients were enrolled in Phase 1 and 10 patients were enrolled in Phase 2 of the study. Overall number of patients enrolled was 20.
|
|
History of metastatic disease
Phase 2
|
9 Participants
n=10 Participants • 10 patients were enrolled in Phase 1 and 10 patients were enrolled in Phase 2 of the study. Overall number of patients enrolled was 20.
|
|
Prior chemotherapy regimen
Phase 1
|
10 Participants
n=10 Participants • 10 patients were enrolled in Phase 1 and 10 patients were enrolled in Phase 2 of the study. Overall number of patients enrolled was 20.
|
|
Prior chemotherapy regimen
Phase 2
|
8 Participants
n=10 Participants • 10 patients were enrolled in Phase 1 and 10 patients were enrolled in Phase 2 of the study. Overall number of patients enrolled was 20.
|
|
Prior radiation
Phase 1
|
7 Participants
n=10 Participants • 10 patients were enrolled in Phase 1 and 10 patients were enrolled in Phase 2 of the study. Overall number of patients enrolled was 20.
|
|
Prior radiation
Phase 2
|
6 Participants
n=10 Participants • 10 patients were enrolled in Phase 1 and 10 patients were enrolled in Phase 2 of the study. Overall number of patients enrolled was 20.
|
|
Prior surgery
Phase 1
|
10 Participants
n=10 Participants • 10 patients were enrolled in Phase 1 and 10 patients were enrolled in Phase 2 of the study. Overall number of patients enrolled was 20.
|
|
Prior surgery
Phase 2
|
9 Participants
n=10 Participants • 10 patients were enrolled in Phase 1 and 10 patients were enrolled in Phase 2 of the study. Overall number of patients enrolled was 20.
|
PRIMARY outcome
Timeframe: Toxicities will be evaluated over the first treatment cycle (each cycle=28 days)Population: 10 patients were enrolled in Phase 1 of the study to determine MTD/RD. Three patients were enrolled in the first dose level. Six patients were enrolled at dose level 2. 1 patient was inevaluable.
To assess the safety, tolerability, and maximum tolerated/ recommended dose of ganetespib when administered in combination with sirolimus in patients with refractory sarcomas or unresectable or metastatic sporadic or neurofibromatosis type 1 (NF1) associated MPNST. Toxicities observed during the first cycle will be used to define the MTD/Recommended dose. Toxicity will be graded using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. DLT will be defined as any of the following events that are possibly, probably, or definitely attributable to ganetespib or sirolimus. The DLT observation period for the purposes of dose escalation will be the first cycle of therapy.
Outcome measures
| Measure |
Ganetespib / Sirolimus
n=9 Participants
28-day cycles of ganetespib + sirolimus
ganetespib: 200 mg/m² IV on days 1, 8, and 15 intravenously over 1 hour
Sirolimus: 2mg taken orally once daily on a continuous dosing schedule; Loading dose 12 mg on cycle 1 day 1 only.
|
Phase 1 Dose Level 2
For each 28-day cycle, subjects took doses of both ganetespib + sirolimus:
ganetespib: 200 mg/m² IV on days 1, 8, and 15 intravenously over 1 hour
Sirolimus: 4mg taken orally once daily on a continuous dosing schedule; Loading dose 12 mg on cycle 1 day 1 only.
|
Phase 2
For each 28-day cycle, subjects took doses of both ganetespib + sirolimus:
ganetespib: 200 mg/m² IV on days 1, 8, and 15 intravenously over 1 hour
Sirolimus: 4mg taken orally once daily on a continuous dosing schedule; Loading dose 12 mg on cycle 1 day 1 only.
|
|---|---|---|---|
|
Number of Dose Limiting Toxicities of Ganetespib When Administered in Combination With Sirolimus.
Dose Level 1
|
0 DLTs
|
—
|
—
|
|
Number of Dose Limiting Toxicities of Ganetespib When Administered in Combination With Sirolimus.
Dose Level 2
|
1 DLTs
|
—
|
—
|
PRIMARY outcome
Timeframe: Response evaluations will be performed after every 2 treatment cycles (each cycle=28 days)Population: 10 patients were enrolled in Phase 1 and 10 patients were enrolled in Phase 2 of the study. Overall number of patients enrolled was 20.
Assessed using the World Health Organization (WHO) criteria. Tumor assessments will be obtained every 2 cycles. Clinical benefit is defined as stable disease, Partial Response (PR), Complete Response (CR). For patients who experience progression by WHO but in the opinion of the treating investigator are deriving benefit from therapy and have not otherwise met off treatment or off study criteria, may continue on treatment as long as patient has not met progression by RECIST 1.1.
Outcome measures
| Measure |
Ganetespib / Sirolimus
n=20 Participants
28-day cycles of ganetespib + sirolimus
ganetespib: 200 mg/m² IV on days 1, 8, and 15 intravenously over 1 hour
Sirolimus: 2mg taken orally once daily on a continuous dosing schedule; Loading dose 12 mg on cycle 1 day 1 only.
|
Phase 1 Dose Level 2
For each 28-day cycle, subjects took doses of both ganetespib + sirolimus:
ganetespib: 200 mg/m² IV on days 1, 8, and 15 intravenously over 1 hour
Sirolimus: 4mg taken orally once daily on a continuous dosing schedule; Loading dose 12 mg on cycle 1 day 1 only.
|
Phase 2
For each 28-day cycle, subjects took doses of both ganetespib + sirolimus:
ganetespib: 200 mg/m² IV on days 1, 8, and 15 intravenously over 1 hour
Sirolimus: 4mg taken orally once daily on a continuous dosing schedule; Loading dose 12 mg on cycle 1 day 1 only.
|
|---|---|---|---|
|
Clinical Benefit of Ganetespib in Combination With Sirolimus
Phase 1
|
1 Participants
|
—
|
—
|
|
Clinical Benefit of Ganetespib in Combination With Sirolimus
Phase 2
|
0 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-therapy levels drawn at baseline and pharmacokinetic analysis occurs on Cycle 1 Day 15Population: 10 patients were enrolled in Phase 1 of the study. Three patients were enrolled in the first dose level. Six patients were enrolled at dose level 2. 1 patient was inevaluable.
To describe the plasma pharmacokinetic profile of ganetespib and sirolimus when administered in combination therapy.
Outcome measures
| Measure |
Ganetespib / Sirolimus
n=9 Participants
28-day cycles of ganetespib + sirolimus
ganetespib: 200 mg/m² IV on days 1, 8, and 15 intravenously over 1 hour
Sirolimus: 2mg taken orally once daily on a continuous dosing schedule; Loading dose 12 mg on cycle 1 day 1 only.
|
Phase 1 Dose Level 2
For each 28-day cycle, subjects took doses of both ganetespib + sirolimus:
ganetespib: 200 mg/m² IV on days 1, 8, and 15 intravenously over 1 hour
Sirolimus: 4mg taken orally once daily on a continuous dosing schedule; Loading dose 12 mg on cycle 1 day 1 only.
|
Phase 2
For each 28-day cycle, subjects took doses of both ganetespib + sirolimus:
ganetespib: 200 mg/m² IV on days 1, 8, and 15 intravenously over 1 hour
Sirolimus: 4mg taken orally once daily on a continuous dosing schedule; Loading dose 12 mg on cycle 1 day 1 only.
|
|---|---|---|---|
|
Change in Plasma Pharmacokinetic Profile of Ganetespib and Sirolimus When Administered in Combination-Observed Maximum Plasma Concentration (Cmax)
Dose Level 1- Sirolimus trough
|
12.1 ng/mL
Standard Deviation 3.6
|
—
|
—
|
|
Change in Plasma Pharmacokinetic Profile of Ganetespib and Sirolimus When Administered in Combination-Observed Maximum Plasma Concentration (Cmax)
Dose Level 2- Sirolimus trough
|
12.5 ng/mL
Standard Deviation 8.9
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and Cycle 1 Day 15Population: 11 subjects provided consent and had adequate specimens for analysis.
To explore changes in pharmacodynamic parameters in peripheral blood mononuclear cells performed on day 1 prior to ganetespib and sirolimus administration, and on day 15, 6 hours post drug administration. Hsp inhibition (Hsp70), mTOR inhibition (phospho-S6 and Akt Phosphorylation), UPR activation (EIF2alpha phosphorylation) will be explored. Western blot analyses were performed for phospho (p)-Akt, p-eIF2α, p-S6, and Hsp70. The absorbance of each phosphoprotein lane was recorded and protein levels were determined after normalizing for levels of corresponding total protein.
Outcome measures
| Measure |
Ganetespib / Sirolimus
n=11 Participants
28-day cycles of ganetespib + sirolimus
ganetespib: 200 mg/m² IV on days 1, 8, and 15 intravenously over 1 hour
Sirolimus: 2mg taken orally once daily on a continuous dosing schedule; Loading dose 12 mg on cycle 1 day 1 only.
|
Phase 1 Dose Level 2
For each 28-day cycle, subjects took doses of both ganetespib + sirolimus:
ganetespib: 200 mg/m² IV on days 1, 8, and 15 intravenously over 1 hour
Sirolimus: 4mg taken orally once daily on a continuous dosing schedule; Loading dose 12 mg on cycle 1 day 1 only.
|
Phase 2
For each 28-day cycle, subjects took doses of both ganetespib + sirolimus:
ganetespib: 200 mg/m² IV on days 1, 8, and 15 intravenously over 1 hour
Sirolimus: 4mg taken orally once daily on a continuous dosing schedule; Loading dose 12 mg on cycle 1 day 1 only.
|
|---|---|---|---|
|
Changes in Pharmacodynamic Parameters in Peripheral Blood Mononuclear Cells
Hsp70 at Baseline
|
0.81 ratio
Standard Deviation 0.39
|
—
|
—
|
|
Changes in Pharmacodynamic Parameters in Peripheral Blood Mononuclear Cells
Hsp70 at Cycle 1 Day 15
|
0.84 ratio
Standard Deviation 0.56
|
—
|
—
|
|
Changes in Pharmacodynamic Parameters in Peripheral Blood Mononuclear Cells
pAKT at Baseline
|
1.20 ratio
Standard Deviation 0.70
|
—
|
—
|
|
Changes in Pharmacodynamic Parameters in Peripheral Blood Mononuclear Cells
pAKT at Cycle 1 Day 15
|
1.44 ratio
Standard Deviation 1.00
|
—
|
—
|
|
Changes in Pharmacodynamic Parameters in Peripheral Blood Mononuclear Cells
p-S6 at Baseline
|
1.25 ratio
Standard Deviation 0.40
|
—
|
—
|
|
Changes in Pharmacodynamic Parameters in Peripheral Blood Mononuclear Cells
p-S6 at Cycle 1 Day 15
|
0.54 ratio
Standard Deviation 0.24
|
—
|
—
|
|
Changes in Pharmacodynamic Parameters in Peripheral Blood Mononuclear Cells
p-eiF2alpha at Baseline
|
1.02 ratio
Standard Deviation 0.26
|
—
|
—
|
|
Changes in Pharmacodynamic Parameters in Peripheral Blood Mononuclear Cells
p-eiF2alpha at Cycle 1 Day 15
|
0.49 ratio
Standard Deviation 0.22
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and prior to Cycle 3Population: Thirteen subjects in phase 1 and phase 2 cohorts combined had MPNST and completed the pain evaluations. 4/13 subjects completed both baseline and pre-cycle 3 evaluations for pain.
To assess patient-reported pain severity and the impact of pain on daily activities before and during treatment with ganetespib and sirolimus. The Numerical Rating Scale-11 (NRS-11) will be used to assess pain severity. The NRS-11 is a self-report segmented 11-point numeric scale that assesses pain severity. It consists of a horizontal line with 0 representing "no pain" at the right end of the line and 10 representing "worst pain you can imagine" at the left end.The Brief Pain Inventory is a 7-item self-report questionnaire that measures the extent to which pain interferes with daily functioning. Patients are asked to indicate how much pain interfered with various activities in the past week, with scores ranging from 0 (does not interfere) to 10 (completely interferes). A total score is obtained by taking the mean of the scores for all 7 items; thus, the total pain interference score can range from 0 to 10.
Outcome measures
| Measure |
Ganetespib / Sirolimus
n=4 Participants
28-day cycles of ganetespib + sirolimus
ganetespib: 200 mg/m² IV on days 1, 8, and 15 intravenously over 1 hour
Sirolimus: 2mg taken orally once daily on a continuous dosing schedule; Loading dose 12 mg on cycle 1 day 1 only.
|
Phase 1 Dose Level 2
For each 28-day cycle, subjects took doses of both ganetespib + sirolimus:
ganetespib: 200 mg/m² IV on days 1, 8, and 15 intravenously over 1 hour
Sirolimus: 4mg taken orally once daily on a continuous dosing schedule; Loading dose 12 mg on cycle 1 day 1 only.
|
Phase 2
For each 28-day cycle, subjects took doses of both ganetespib + sirolimus:
ganetespib: 200 mg/m² IV on days 1, 8, and 15 intravenously over 1 hour
Sirolimus: 4mg taken orally once daily on a continuous dosing schedule; Loading dose 12 mg on cycle 1 day 1 only.
|
|---|---|---|---|
|
Patient-reported Pain Severity and the Impact of Pain on Daily Activities
Baseline- Tumor pain intensity
|
7.5 units on a scale
Interval 0.0 to 10.0
|
—
|
—
|
|
Patient-reported Pain Severity and the Impact of Pain on Daily Activities
Baseline- Overall pain intensity
|
7.5 units on a scale
Interval 0.0 to 10.0
|
—
|
—
|
|
Patient-reported Pain Severity and the Impact of Pain on Daily Activities
Baseline- Pain interference
|
6.49 units on a scale
Interval 0.0 to 10.0
|
—
|
—
|
|
Patient-reported Pain Severity and the Impact of Pain on Daily Activities
Prior to Cycle 3- Overall pain intensity
|
5 units on a scale
Interval 0.0 to 10.0
|
—
|
—
|
|
Patient-reported Pain Severity and the Impact of Pain on Daily Activities
Prior to Cycle 3- Tumor pain intensity
|
4.75 units on a scale
Interval 0.0 to 10.0
|
—
|
—
|
|
Patient-reported Pain Severity and the Impact of Pain on Daily Activities
Prior to Cycle 3- Pain interference
|
3.14 units on a scale
Interval 0.0 to 10.0
|
—
|
—
|
SECONDARY outcome
Timeframe: 4 monthsPopulation: The 3D-MRI were not measurable with current modalities. Due to their nature and incomplete imaging, volumetric analysis was not feasible.
To evaluate the utility of three-dimensional MRI (3D-MRI) analysis in comparison to 1-dimensional and 2-dimensional measurements as a method to more sensitively monitor response.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Cycle 1 Day 15Population: 10 patients were enrolled in Phase 1 of the study. 1 patient was inevaluable.
To describe the plasma pharmacokinetic profile of ganetespib in terms of half life.
Outcome measures
| Measure |
Ganetespib / Sirolimus
n=9 Participants
28-day cycles of ganetespib + sirolimus
ganetespib: 200 mg/m² IV on days 1, 8, and 15 intravenously over 1 hour
Sirolimus: 2mg taken orally once daily on a continuous dosing schedule; Loading dose 12 mg on cycle 1 day 1 only.
|
Phase 1 Dose Level 2
For each 28-day cycle, subjects took doses of both ganetespib + sirolimus:
ganetespib: 200 mg/m² IV on days 1, 8, and 15 intravenously over 1 hour
Sirolimus: 4mg taken orally once daily on a continuous dosing schedule; Loading dose 12 mg on cycle 1 day 1 only.
|
Phase 2
For each 28-day cycle, subjects took doses of both ganetespib + sirolimus:
ganetespib: 200 mg/m² IV on days 1, 8, and 15 intravenously over 1 hour
Sirolimus: 4mg taken orally once daily on a continuous dosing schedule; Loading dose 12 mg on cycle 1 day 1 only.
|
|---|---|---|---|
|
Plasma Pharmacokinetic Profile of Ganetespib When Administered in Combination With Sirolimus
Ganetespib half life for dose level 1
|
6.4 hours
Standard Deviation 2.1
|
—
|
—
|
|
Plasma Pharmacokinetic Profile of Ganetespib When Administered in Combination With Sirolimus
Ganetespib half life for dose level 2
|
6.0 hours
Standard Deviation 0.9
|
—
|
—
|
SECONDARY outcome
Timeframe: Phase 1 of studyPopulation: 1 patient was inevaluable in Phase 1 of study. The recommended dose of ganetespib was determined to be 200 mg/m2 intravenously on days 1, 8, 15 with sirolimus 4mg orally once daily with a cycle 1 day 1 loading dose of 12mg. All patients in phase 2 were treated with the recommended dose.
A conventional 3+3 dose escalation design was used for phase 1. All patients in phase 2 were treated with the recommended dose.
Outcome measures
| Measure |
Ganetespib / Sirolimus
n=3 Participants
28-day cycles of ganetespib + sirolimus
ganetespib: 200 mg/m² IV on days 1, 8, and 15 intravenously over 1 hour
Sirolimus: 2mg taken orally once daily on a continuous dosing schedule; Loading dose 12 mg on cycle 1 day 1 only.
|
Phase 1 Dose Level 2
n=6 Participants
For each 28-day cycle, subjects took doses of both ganetespib + sirolimus:
ganetespib: 200 mg/m² IV on days 1, 8, and 15 intravenously over 1 hour
Sirolimus: 4mg taken orally once daily on a continuous dosing schedule; Loading dose 12 mg on cycle 1 day 1 only.
|
Phase 2
n=10 Participants
For each 28-day cycle, subjects took doses of both ganetespib + sirolimus:
ganetespib: 200 mg/m² IV on days 1, 8, and 15 intravenously over 1 hour
Sirolimus: 4mg taken orally once daily on a continuous dosing schedule; Loading dose 12 mg on cycle 1 day 1 only.
|
|---|---|---|---|
|
Determine Maximum Tolerated Dose (MTD)/Recommended Dose (RD) of Ganetespib
|
3 Participants
|
6 Participants
|
10 Participants
|
Adverse Events
Phase 1 Dose 1
Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths
Phase 1 Dose 2
Serious events: 2 serious events
Other events: 7 other events
Deaths: 1 deaths
Phase 2
Serious events: 6 serious events
Other events: 10 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Phase 1 Dose 1
n=3 participants at risk
For each 28-day cycle, subjects took doses of both ganetespib + sirolimus:
ganetespib: 150 mg/m² IV on days 1, 8, and 15 intravenously over 1 hour
Sirolimus: 4mg taken orally once daily on a continuous dosing schedule; Loading dose 12 mg on cycle 1 day 1 only.
|
Phase 1 Dose 2
n=7 participants at risk
For each 28-day cycle, subjects took doses of both ganetespib + sirolimus:
ganetespib: 200 mg/m² IV on days 1, 8, and 15 intravenously over 1 hour
Sirolimus: 4mg taken orally once daily on a continuous dosing schedule; Loading dose 12 mg on cycle 1 day 1 only.
|
Phase 2
n=10 participants at risk
For each 28-day cycle, subjects took doses of both ganetespib + sirolimus:
ganetespib: 200 mg/m² IV on days 1, 8, and 15 intravenously over 1 hour
Sirolimus: 4mg taken orally once daily on a continuous dosing schedule; Loading dose 12 mg on cycle 1 day 1 only.
|
|---|---|---|---|
|
Gastrointestinal disorders
Gastrointestinal disorders- other
|
0.00%
0/3 • 3 years
|
0.00%
0/7 • 3 years
|
10.0%
1/10 • Number of events 1 • 3 years
|
|
Investigations
Alanine Aminotransferase increased
|
0.00%
0/3 • 3 years
|
0.00%
0/7 • 3 years
|
10.0%
1/10 • Number of events 1 • 3 years
|
|
Investigations
Aspartate Aminotransferase increased
|
0.00%
0/3 • 3 years
|
0.00%
0/7 • 3 years
|
10.0%
1/10 • Number of events 1 • 3 years
|
|
Hepatobiliary disorders
Cholecystitis
|
0.00%
0/3 • 3 years
|
14.3%
1/7 • Number of events 1 • 3 years
|
10.0%
1/10 • Number of events 1 • 3 years
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/3 • 3 years
|
0.00%
0/7 • 3 years
|
10.0%
1/10 • Number of events 1 • 3 years
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/3 • 3 years
|
0.00%
0/7 • 3 years
|
10.0%
1/10 • Number of events 1 • 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
33.3%
1/3 • Number of events 1 • 3 years
|
0.00%
0/7 • 3 years
|
0.00%
0/10 • 3 years
|
|
General disorders
Fever
|
0.00%
0/3 • 3 years
|
14.3%
1/7 • Number of events 1 • 3 years
|
0.00%
0/10 • 3 years
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
33.3%
1/3 • Number of events 1 • 3 years
|
0.00%
0/7 • 3 years
|
0.00%
0/10 • 3 years
|
|
General disorders
Infusion related reaction
|
0.00%
0/3 • 3 years
|
14.3%
1/7 • Number of events 1 • 3 years
|
0.00%
0/10 • 3 years
|
|
Infections and infestations
Lung infection
|
0.00%
0/3 • 3 years
|
0.00%
0/7 • 3 years
|
10.0%
1/10 • Number of events 1 • 3 years
|
|
Investigations
Lymphocyte count decreased
|
0.00%
0/3 • 3 years
|
0.00%
0/7 • 3 years
|
10.0%
1/10 • Number of events 1 • 3 years
|
|
Gastrointestinal disorders
Gastric obstruction
|
0.00%
0/3 • 3 years
|
0.00%
0/7 • 3 years
|
10.0%
1/10 • Number of events 1 • 3 years
|
|
Vascular disorders
Thromboembolic event
|
0.00%
0/3 • 3 years
|
0.00%
0/7 • 3 years
|
10.0%
1/10 • Number of events 1 • 3 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain
|
0.00%
0/3 • 3 years
|
0.00%
0/7 • 3 years
|
10.0%
1/10 • Number of events 1 • 3 years
|
|
Renal and urinary disorders
Urinary retention
|
0.00%
0/3 • 3 years
|
0.00%
0/7 • 3 years
|
10.0%
1/10 • Number of events 1 • 3 years
|
Other adverse events
| Measure |
Phase 1 Dose 1
n=3 participants at risk
For each 28-day cycle, subjects took doses of both ganetespib + sirolimus:
ganetespib: 150 mg/m² IV on days 1, 8, and 15 intravenously over 1 hour
Sirolimus: 4mg taken orally once daily on a continuous dosing schedule; Loading dose 12 mg on cycle 1 day 1 only.
|
Phase 1 Dose 2
n=7 participants at risk
For each 28-day cycle, subjects took doses of both ganetespib + sirolimus:
ganetespib: 200 mg/m² IV on days 1, 8, and 15 intravenously over 1 hour
Sirolimus: 4mg taken orally once daily on a continuous dosing schedule; Loading dose 12 mg on cycle 1 day 1 only.
|
Phase 2
n=10 participants at risk
For each 28-day cycle, subjects took doses of both ganetespib + sirolimus:
ganetespib: 200 mg/m² IV on days 1, 8, and 15 intravenously over 1 hour
Sirolimus: 4mg taken orally once daily on a continuous dosing schedule; Loading dose 12 mg on cycle 1 day 1 only.
|
|---|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/3 • 3 years
|
0.00%
0/7 • 3 years
|
20.0%
2/10 • Number of events 2 • 3 years
|
|
Investigations
Activated Partial Thromboplastin Time Prolonged
|
0.00%
0/3 • 3 years
|
28.6%
2/7 • Number of events 2 • 3 years
|
30.0%
3/10 • Number of events 3 • 3 years
|
|
Investigations
Alanine Aminotransferase increased
|
33.3%
1/3 • Number of events 3 • 3 years
|
14.3%
1/7 • Number of events 2 • 3 years
|
20.0%
2/10 • Number of events 8 • 3 years
|
|
Investigations
Alkaline Phosphatase increased
|
33.3%
1/3 • Number of events 1 • 3 years
|
14.3%
1/7 • Number of events 2 • 3 years
|
50.0%
5/10 • Number of events 9 • 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Allergic Rhinitis
|
0.00%
0/3 • 3 years
|
0.00%
0/7 • 3 years
|
20.0%
2/10 • Number of events 2 • 3 years
|
|
Blood and lymphatic system disorders
Anemia
|
33.3%
1/3 • Number of events 1 • 3 years
|
28.6%
2/7 • Number of events 4 • 3 years
|
30.0%
3/10 • Number of events 3 • 3 years
|
|
Metabolism and nutrition disorders
Anorexia
|
66.7%
2/3 • Number of events 3 • 3 years
|
0.00%
0/7 • 3 years
|
10.0%
1/10 • Number of events 2 • 3 years
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
33.3%
1/3 • Number of events 1 • 3 years
|
0.00%
0/7 • 3 years
|
0.00%
0/10 • 3 years
|
|
Investigations
Aspartate Aminotransferase increased
|
66.7%
2/3 • Number of events 2 • 3 years
|
14.3%
1/7 • Number of events 2 • 3 years
|
30.0%
3/10 • Number of events 6 • 3 years
|
|
Nervous system disorders
Ataxia
|
0.00%
0/3 • 3 years
|
14.3%
1/7 • Number of events 1 • 3 years
|
0.00%
0/10 • 3 years
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
33.3%
1/3 • Number of events 1 • 3 years
|
14.3%
1/7 • Number of events 1 • 3 years
|
10.0%
1/10 • Number of events 1 • 3 years
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/3 • 3 years
|
14.3%
1/7 • Number of events 1 • 3 years
|
10.0%
1/10 • Number of events 2 • 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Bronchopulmonary hemorrhage
|
0.00%
0/3 • 3 years
|
0.00%
0/7 • 3 years
|
10.0%
1/10 • Number of events 1 • 3 years
|
|
Injury, poisoning and procedural complications
Bruising
|
33.3%
1/3 • Number of events 1 • 3 years
|
0.00%
0/7 • 3 years
|
0.00%
0/10 • 3 years
|
|
Gastrointestinal disorders
Cheilitis
|
33.3%
1/3 • Number of events 1 • 3 years
|
0.00%
0/7 • 3 years
|
0.00%
0/10 • 3 years
|
|
Musculoskeletal and connective tissue disorders
Chest wall pain
|
0.00%
0/3 • 3 years
|
28.6%
2/7 • Number of events 2 • 3 years
|
0.00%
0/10 • 3 years
|
|
General disorders
Chills
|
0.00%
0/3 • 3 years
|
14.3%
1/7 • Number of events 1 • 3 years
|
0.00%
0/10 • 3 years
|
|
Investigations
High cholesterol
|
0.00%
0/3 • 3 years
|
28.6%
2/7 • Number of events 3 • 3 years
|
0.00%
0/10 • 3 years
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/3 • 3 years
|
0.00%
0/7 • 3 years
|
10.0%
1/10 • Number of events 1 • 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
66.7%
2/3 • Number of events 2 • 3 years
|
0.00%
0/7 • 3 years
|
10.0%
1/10 • Number of events 1 • 3 years
|
|
Investigations
CPK increased
|
0.00%
0/3 • 3 years
|
14.3%
1/7 • Number of events 2 • 3 years
|
0.00%
0/10 • 3 years
|
|
Investigations
Creatinine increased
|
0.00%
0/3 • 3 years
|
28.6%
2/7 • Number of events 2 • 3 years
|
20.0%
2/10 • Number of events 2 • 3 years
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/3 • 3 years
|
0.00%
0/7 • 3 years
|
10.0%
1/10 • Number of events 1 • 3 years
|
|
Gastrointestinal disorders
Dental caries
|
0.00%
0/3 • 3 years
|
14.3%
1/7 • Number of events 1 • 3 years
|
0.00%
0/10 • 3 years
|
|
Gastrointestinal disorders
Diarrhea
|
66.7%
2/3 • Number of events 5 • 3 years
|
100.0%
7/7 • Number of events 11 • 3 years
|
80.0%
8/10 • Number of events 14 • 3 years
|
|
Eye disorders
Dry eye
|
0.00%
0/3 • 3 years
|
14.3%
1/7 • Number of events 1 • 3 years
|
0.00%
0/10 • 3 years
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/3 • 3 years
|
28.6%
2/7 • Number of events 2 • 3 years
|
20.0%
2/10 • Number of events 2 • 3 years
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
0.00%
0/3 • 3 years
|
14.3%
1/7 • Number of events 1 • 3 years
|
0.00%
0/10 • 3 years
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/3 • 3 years
|
0.00%
0/7 • 3 years
|
10.0%
1/10 • Number of events 1 • 3 years
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/3 • 3 years
|
14.3%
1/7 • Number of events 1 • 3 years
|
0.00%
0/10 • 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
33.3%
1/3 • Number of events 1 • 3 years
|
0.00%
0/7 • 3 years
|
10.0%
1/10 • Number of events 1 • 3 years
|
|
General disorders
Edema limbs
|
0.00%
0/3 • 3 years
|
28.6%
2/7 • Number of events 3 • 3 years
|
10.0%
1/10 • Number of events 1 • 3 years
|
|
General disorders
Edema trunk
|
0.00%
0/3 • 3 years
|
14.3%
1/7 • Number of events 1 • 3 years
|
0.00%
0/10 • 3 years
|
|
Reproductive system and breast disorders
Erectile Dysfunction
|
0.00%
0/3 • 3 years
|
14.3%
1/7 • Number of events 1 • 3 years
|
0.00%
0/10 • 3 years
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/3 • 3 years
|
0.00%
0/7 • 3 years
|
10.0%
1/10 • Number of events 1 • 3 years
|
|
General disorders
Fatigue
|
66.7%
2/3 • Number of events 3 • 3 years
|
14.3%
1/7 • Number of events 1 • 3 years
|
60.0%
6/10 • Number of events 6 • 3 years
|
|
General disorders
Fever
|
0.00%
0/3 • 3 years
|
14.3%
1/7 • Number of events 1 • 3 years
|
20.0%
2/10 • Number of events 2 • 3 years
|
|
Hepatobiliary disorders
Gallbladder pain
|
0.00%
0/3 • 3 years
|
14.3%
1/7 • Number of events 1 • 3 years
|
0.00%
0/10 • 3 years
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
0.00%
0/3 • 3 years
|
0.00%
0/7 • 3 years
|
10.0%
1/10 • Number of events 1 • 3 years
|
|
Gastrointestinal disorders
Gastrointestinal disorders-other
|
0.00%
0/3 • 3 years
|
14.3%
1/7 • Number of events 1 • 3 years
|
20.0%
2/10 • Number of events 2 • 3 years
|
|
Gastrointestinal disorders
Gastrointestinal pain
|
0.00%
0/3 • 3 years
|
14.3%
1/7 • Number of events 1 • 3 years
|
0.00%
0/10 • 3 years
|
|
General disorders
General disorders and admin site conditions-other
|
33.3%
1/3 • Number of events 3 • 3 years
|
0.00%
0/7 • 3 years
|
10.0%
1/10 • Number of events 2 • 3 years
|
|
Nervous system disorders
Headache
|
66.7%
2/3 • Number of events 4 • 3 years
|
42.9%
3/7 • Number of events 3 • 3 years
|
0.00%
0/10 • 3 years
|
|
Gastrointestinal disorders
Hemorrhoids
|
0.00%
0/3 • 3 years
|
14.3%
1/7 • Number of events 1 • 3 years
|
0.00%
0/10 • 3 years
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
0.00%
0/3 • 3 years
|
0.00%
0/7 • 3 years
|
10.0%
1/10 • Number of events 1 • 3 years
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
66.7%
2/3 • Number of events 3 • 3 years
|
28.6%
2/7 • Number of events 3 • 3 years
|
20.0%
2/10 • Number of events 2 • 3 years
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/3 • 3 years
|
14.3%
1/7 • Number of events 2 • 3 years
|
0.00%
0/10 • 3 years
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
0.00%
0/3 • 3 years
|
14.3%
1/7 • Number of events 1 • 3 years
|
0.00%
0/10 • 3 years
|
|
Vascular disorders
Hypertension
|
0.00%
0/3 • 3 years
|
0.00%
0/7 • 3 years
|
20.0%
2/10 • Number of events 4 • 3 years
|
|
Metabolism and nutrition disorders
Hypertriglyceridemia
|
0.00%
0/3 • 3 years
|
28.6%
2/7 • Number of events 5 • 3 years
|
0.00%
0/10 • 3 years
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
0.00%
0/3 • 3 years
|
14.3%
1/7 • Number of events 3 • 3 years
|
30.0%
3/10 • Number of events 4 • 3 years
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
0.00%
0/3 • 3 years
|
0.00%
0/7 • 3 years
|
10.0%
1/10 • Number of events 1 • 3 years
|
|
Metabolism and nutrition disorders
Hypokalemia
|
33.3%
1/3 • Number of events 2 • 3 years
|
0.00%
0/7 • 3 years
|
10.0%
1/10 • Number of events 1 • 3 years
|
|
Metabolism and nutrition disorders
Hyponatremia
|
0.00%
0/3 • 3 years
|
28.6%
2/7 • Number of events 3 • 3 years
|
40.0%
4/10 • Number of events 4 • 3 years
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
66.7%
2/3 • Number of events 2 • 3 years
|
14.3%
1/7 • Number of events 1 • 3 years
|
10.0%
1/10 • Number of events 1 • 3 years
|
|
Infections and infestations
Infections and infestations-other
|
0.00%
0/3 • 3 years
|
0.00%
0/7 • 3 years
|
10.0%
1/10 • Number of events 1 • 3 years
|
|
General disorders
Infusion related reaction
|
0.00%
0/3 • 3 years
|
28.6%
2/7 • Number of events 2 • 3 years
|
10.0%
1/10 • Number of events 1 • 3 years
|
|
Psychiatric disorders
Insomnia
|
33.3%
1/3 • Number of events 1 • 3 years
|
28.6%
2/7 • Number of events 2 • 3 years
|
10.0%
1/10 • Number of events 1 • 3 years
|
|
Investigations
Investigations-other
|
33.3%
1/3 • Number of events 1 • 3 years
|
0.00%
0/7 • 3 years
|
0.00%
0/10 • 3 years
|
|
General disorders
Irritability
|
0.00%
0/3 • 3 years
|
14.3%
1/7 • Number of events 2 • 3 years
|
0.00%
0/10 • 3 years
|
|
Psychiatric disorders
Libido decreased
|
0.00%
0/3 • 3 years
|
14.3%
1/7 • Number of events 1 • 3 years
|
0.00%
0/10 • 3 years
|
|
Infections and infestations
Lung infection
|
33.3%
1/3 • Number of events 1 • 3 years
|
0.00%
0/7 • 3 years
|
0.00%
0/10 • 3 years
|
|
Investigations
Lymphocyte count decreased
|
66.7%
2/3 • Number of events 3 • 3 years
|
42.9%
3/7 • Number of events 8 • 3 years
|
40.0%
4/10 • Number of events 8 • 3 years
|
|
Gastrointestinal disorders
Mucositis oral
|
66.7%
2/3 • Number of events 2 • 3 years
|
28.6%
2/7 • Number of events 4 • 3 years
|
10.0%
1/10 • Number of events 1 • 3 years
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness lower limb
|
0.00%
0/3 • 3 years
|
0.00%
0/7 • 3 years
|
10.0%
1/10 • Number of events 1 • 3 years
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorder-other
|
0.00%
0/3 • 3 years
|
14.3%
1/7 • Number of events 1 • 3 years
|
10.0%
1/10 • Number of events 1 • 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
33.3%
1/3 • Number of events 1 • 3 years
|
14.3%
1/7 • Number of events 1 • 3 years
|
10.0%
1/10 • Number of events 1 • 3 years
|
|
Gastrointestinal disorders
Nausea
|
33.3%
1/3 • Number of events 2 • 3 years
|
42.9%
3/7 • Number of events 3 • 3 years
|
70.0%
7/10 • Number of events 9 • 3 years
|
|
Investigations
Neutrophil count decreased
|
33.3%
1/3 • Number of events 3 • 3 years
|
0.00%
0/7 • 3 years
|
10.0%
1/10 • Number of events 1 • 3 years
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/3 • 3 years
|
28.6%
2/7 • Number of events 2 • 3 years
|
0.00%
0/10 • 3 years
|
|
Gastrointestinal disorders
Oral pain
|
0.00%
0/3 • 3 years
|
14.3%
1/7 • Number of events 1 • 3 years
|
0.00%
0/10 • 3 years
|
|
General disorders
Pain
|
0.00%
0/3 • 3 years
|
14.3%
1/7 • Number of events 1 • 3 years
|
0.00%
0/10 • 3 years
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/3 • 3 years
|
14.3%
1/7 • Number of events 1 • 3 years
|
0.00%
0/10 • 3 years
|
|
Investigations
Platelet count decreased
|
66.7%
2/3 • Number of events 2 • 3 years
|
42.9%
3/7 • Number of events 7 • 3 years
|
20.0%
2/10 • Number of events 2 • 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/3 • 3 years
|
0.00%
0/7 • 3 years
|
10.0%
1/10 • Number of events 1 • 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Postnasal drip
|
0.00%
0/3 • 3 years
|
14.3%
1/7 • Number of events 1 • 3 years
|
0.00%
0/10 • 3 years
|
|
Renal and urinary disorders
Proteinuria
|
0.00%
0/3 • 3 years
|
14.3%
1/7 • Number of events 1 • 3 years
|
10.0%
1/10 • Number of events 1 • 3 years
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/3 • 3 years
|
28.6%
2/7 • Number of events 2 • 3 years
|
0.00%
0/10 • 3 years
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
0.00%
0/3 • 3 years
|
14.3%
1/7 • Number of events 1 • 3 years
|
0.00%
0/10 • 3 years
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
33.3%
1/3 • Number of events 1 • 3 years
|
28.6%
2/7 • Number of events 2 • 3 years
|
10.0%
1/10 • Number of events 1 • 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders-other
|
33.3%
1/3 • Number of events 1 • 3 years
|
0.00%
0/7 • 3 years
|
0.00%
0/10 • 3 years
|
|
Cardiac disorders
Sinus tachycardia
|
0.00%
0/3 • 3 years
|
0.00%
0/7 • 3 years
|
20.0%
2/10 • Number of events 2 • 3 years
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders-other
|
0.00%
0/3 • 3 years
|
14.3%
1/7 • Number of events 1 • 3 years
|
10.0%
1/10 • Number of events 1 • 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Sore throat
|
0.00%
0/3 • 3 years
|
14.3%
1/7 • Number of events 1 • 3 years
|
10.0%
1/10 • Number of events 1 • 3 years
|
|
Surgical and medical procedures
Surgical and medical procedures-other
|
0.00%
0/3 • 3 years
|
14.3%
1/7 • Number of events 1 • 3 years
|
0.00%
0/10 • 3 years
|
|
Vascular disorders
Thromboembolic event
|
33.3%
1/3 • Number of events 1 • 3 years
|
14.3%
1/7 • Number of events 1 • 3 years
|
0.00%
0/10 • 3 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain
|
0.00%
0/3 • 3 years
|
14.3%
1/7 • Number of events 1 • 3 years
|
0.00%
0/10 • 3 years
|
|
Renal and urinary disorders
Urinary frequency
|
33.3%
1/3 • Number of events 1 • 3 years
|
0.00%
0/7 • 3 years
|
0.00%
0/10 • 3 years
|
|
Gastrointestinal disorders
Vomiting
|
33.3%
1/3 • Number of events 1 • 3 years
|
14.3%
1/7 • Number of events 1 • 3 years
|
50.0%
5/10 • Number of events 6 • 3 years
|
|
Investigations
Weight loss
|
0.00%
0/3 • 3 years
|
14.3%
1/7 • Number of events 1 • 3 years
|
0.00%
0/10 • 3 years
|
|
Investigations
White blood cell decreased
|
66.7%
2/3 • Number of events 3 • 3 years
|
0.00%
0/7 • 3 years
|
20.0%
2/10 • Number of events 2 • 3 years
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place