Trial Outcomes & Findings for Vismodegib and Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Advanced or Metastatic Sarcoma (NCT NCT01154452)
NCT ID: NCT01154452
Last Updated: 2018-08-15
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
78 participants
Primary outcome timeframe
Up to 28 days
Results posted on
2018-08-15
Participant Flow
Participant milestones
| Measure |
RO4929097 10mg
RO4929097: 10mg PO QD, GDC-0449: 150 mg PO QD
|
RO4929097 15 mg
RO4929097: 15 mg PO QD, GDC-0449: 150 mg PO QD
|
ARM 1 - RO4929097: 15 mg PO QD
ARM 1 - RO4929097: 15 mg PO QD
|
ARM 2: GDC-0449 150 mg PO QD and RO4929097 15 mg PO QD
ARM 2: GDC-0449 150 mg PO QD and RO4929097 15 mg PO QD
|
|---|---|---|---|---|
|
Phase Ib
STARTED
|
6
|
4
|
0
|
0
|
|
Phase Ib
COMPLETED
|
3
|
3
|
0
|
0
|
|
Phase Ib
NOT COMPLETED
|
3
|
1
|
0
|
0
|
|
Phase II
STARTED
|
0
|
0
|
35
|
33
|
|
Phase II
COMPLETED
|
0
|
0
|
30
|
27
|
|
Phase II
NOT COMPLETED
|
0
|
0
|
5
|
6
|
Reasons for withdrawal
| Measure |
RO4929097 10mg
RO4929097: 10mg PO QD, GDC-0449: 150 mg PO QD
|
RO4929097 15 mg
RO4929097: 15 mg PO QD, GDC-0449: 150 mg PO QD
|
ARM 1 - RO4929097: 15 mg PO QD
ARM 1 - RO4929097: 15 mg PO QD
|
ARM 2: GDC-0449 150 mg PO QD and RO4929097 15 mg PO QD
ARM 2: GDC-0449 150 mg PO QD and RO4929097 15 mg PO QD
|
|---|---|---|---|---|
|
Phase Ib
Not Treated
|
1
|
0
|
0
|
0
|
|
Phase Ib
Adverse Event
|
2
|
1
|
0
|
0
|
|
Phase II
Withdrawal by Subject
|
0
|
0
|
1
|
2
|
|
Phase II
Adverse Event
|
0
|
0
|
4
|
4
|
Baseline Characteristics
Vismodegib and Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Advanced or Metastatic Sarcoma
Baseline characteristics by cohort
| Measure |
RO4929097 10mg
n=6 Participants
RO4929097: 10mg PO QD, GDC-0449: 150 mg PO QD
|
RO4929097 15 mg
n=4 Participants
RO4929097: 15 mg PO QD, GDC-0449: 150 mg PO QD
|
ARM 1 - RO4929097: 15 mg PO QD
n=35 Participants
ARM 1 - RO4929097: 15 mg PO QD
|
ARM 2: GDC-0449 150 mg PO QD and RO4929097 15 mg PO QD
n=33 Participants
ARM 2: GDC-0449 150 mg PO QD and RO4929097 15 mg PO QD
|
Total
n=78 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
6 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
25 Participants
n=5 Participants
|
27 Participants
n=4 Participants
|
61 Participants
n=21 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
17 Participants
n=21 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
15 Participants
n=4 Participants
|
34 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
18 Participants
n=4 Participants
|
44 Participants
n=21 Participants
|
|
Region of Enrollment
United States
|
6 participants
n=5 Participants
|
4 participants
n=7 Participants
|
35 participants
n=5 Participants
|
33 participants
n=4 Participants
|
78 participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Up to 28 daysOutcome measures
| Measure |
All Phase Ib Participants
n=10 Participants
All Phase Ib Participants
|
Arm II (Vismodegib and Gamma-secretase Inhibitor RO4929097)
Patients receive vismodegib PO and gamma-secretase/Notch signalling pathway inhibitor RO4929097 PO QD on days 1-21.
Gamma-Secretase Inhibitor RO4929097: Given PO
Laboratory Biomarker Analysis: Correlative studies
Pharmacological Study: Correlative studies
Vismodegib: Given PO
|
ARM 1 - RO4929097: 15 mg PO QD
ARM 1 - RO4929097: 15 mg PO QD
|
ARM 2: GDC-0449 150 mg PO QD and RO4929097 15 mg PO QD
ARM 2: GDC-0449 150 mg PO QD and RO4929097 15 mg PO QD
|
|---|---|---|---|---|
|
Maximum-tolerated Dose of Gamma-secretase Inhibitor RO4929097, Defined as the Dose Level Where no More Than 1 Out of 6 Patients Experience DLT at the Highest Dose Level Below the MAD, Graded According to NCI-CTCAE Version 4.0 (Phase Ib)
|
15 mg
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: 6 weeksProgression-free survival (PFS) of the combination of RO4929097 with and without GDC-0449 in patients with advanced sarcoma. (Phase II)
Outcome measures
| Measure |
All Phase Ib Participants
n=35 Participants
All Phase Ib Participants
|
Arm II (Vismodegib and Gamma-secretase Inhibitor RO4929097)
n=33 Participants
Patients receive vismodegib PO and gamma-secretase/Notch signalling pathway inhibitor RO4929097 PO QD on days 1-21.
Gamma-Secretase Inhibitor RO4929097: Given PO
Laboratory Biomarker Analysis: Correlative studies
Pharmacological Study: Correlative studies
Vismodegib: Given PO
|
ARM 1 - RO4929097: 15 mg PO QD
ARM 1 - RO4929097: 15 mg PO QD
|
ARM 2: GDC-0449 150 mg PO QD and RO4929097 15 mg PO QD
ARM 2: GDC-0449 150 mg PO QD and RO4929097 15 mg PO QD
|
|---|---|---|---|---|
|
Progression-free Survival (PFS)
|
60 percentage of participants
|
60 percentage of participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 4 monthsPer Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions
Outcome measures
| Measure |
All Phase Ib Participants
n=3 Participants
All Phase Ib Participants
|
Arm II (Vismodegib and Gamma-secretase Inhibitor RO4929097)
n=3 Participants
Patients receive vismodegib PO and gamma-secretase/Notch signalling pathway inhibitor RO4929097 PO QD on days 1-21.
Gamma-Secretase Inhibitor RO4929097: Given PO
Laboratory Biomarker Analysis: Correlative studies
Pharmacological Study: Correlative studies
Vismodegib: Given PO
|
ARM 1 - RO4929097: 15 mg PO QD
n=30 Participants
ARM 1 - RO4929097: 15 mg PO QD
|
ARM 2: GDC-0449 150 mg PO QD and RO4929097 15 mg PO QD
n=27 Participants
ARM 2: GDC-0449 150 mg PO QD and RO4929097 15 mg PO QD
|
|---|---|---|---|---|
|
Response Rate (CR + PR) as Assessed by RECIST 1.1 (Phase Ib and II)
Stable Disease
|
2 participants
|
2 participants
|
17 participants
|
16 participants
|
|
Response Rate (CR + PR) as Assessed by RECIST 1.1 (Phase Ib and II)
Progression of Disease
|
1 participants
|
1 participants
|
13 participants
|
11 participants
|
Adverse Events
RO4929097 10mg
Serious events: 2 serious events
Other events: 4 other events
Deaths: 0 deaths
RO4929097 15 mg
Serious events: 2 serious events
Other events: 4 other events
Deaths: 0 deaths
ARM 1 - RO4929097: 15 mg PO QD
Serious events: 11 serious events
Other events: 26 other events
Deaths: 0 deaths
ARM 2: GDC-0449 150 mg PO QD and RO4929097 15 mg PO QD
Serious events: 8 serious events
Other events: 23 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
RO4929097 10mg
n=6 participants at risk
RO4929097: 10mg PO QD, GDC-0449: 150 mg PO QD
|
RO4929097 15 mg
n=4 participants at risk
RO4929097: 15 mg PO QD, GDC-0449: 150 mg PO QD
|
ARM 1 - RO4929097: 15 mg PO QD
n=35 participants at risk
ARM 1 - RO4929097: 15 mg PO QD
|
ARM 2: GDC-0449 150 mg PO QD and RO4929097 15 mg PO QD
n=33 participants at risk
ARM 2: GDC-0449 150 mg PO QD and RO4929097 15 mg PO QD
|
|---|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Pleuritic pain
|
16.7%
1/6 • Number of events 1
|
0.00%
0/4
|
0.00%
0/35
|
0.00%
0/33
|
|
General disorders
Death NOS
|
16.7%
1/6 • Number of events 1
|
0.00%
0/4
|
0.00%
0/35
|
0.00%
0/33
|
|
Gastrointestinal disorders
Dysphagia
|
16.7%
1/6 • Number of events 1
|
0.00%
0/4
|
0.00%
0/35
|
0.00%
0/33
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
16.7%
1/6 • Number of events 1
|
25.0%
1/4 • Number of events 2
|
0.00%
0/35
|
0.00%
0/33
|
|
Investigations
Lymphocyte count decreased
|
16.7%
1/6 • Number of events 1
|
25.0%
1/4 • Number of events 1
|
5.7%
2/35 • Number of events 3
|
0.00%
0/33
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
16.7%
1/6 • Number of events 1
|
0.00%
0/4
|
0.00%
0/35
|
0.00%
0/33
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.00%
0/6
|
25.0%
1/4 • Number of events 1
|
2.9%
1/35 • Number of events 1
|
0.00%
0/33
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/6
|
25.0%
1/4 • Number of events 1
|
0.00%
0/35
|
0.00%
0/33
|
|
Infections and infestations
Wound infection
|
0.00%
0/6
|
25.0%
1/4 • Number of events 1
|
0.00%
0/35
|
0.00%
0/33
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/6
|
0.00%
0/4
|
2.9%
1/35 • Number of events 1
|
3.0%
1/33 • Number of events 1
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/6
|
0.00%
0/4
|
5.7%
2/35 • Number of events 2
|
0.00%
0/33
|
|
Investigations
Alkaline phosphatase increased
|
0.00%
0/6
|
0.00%
0/4
|
2.9%
1/35 • Number of events 1
|
0.00%
0/33
|
|
Blood and lymphatic system disorders
Anemia
|
0.00%
0/6
|
0.00%
0/4
|
5.7%
2/35 • Number of events 2
|
3.0%
1/33 • Number of events 1
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/6
|
0.00%
0/4
|
2.9%
1/35 • Number of events 1
|
0.00%
0/33
|
|
Infections and infestations
Lung infection
|
0.00%
0/6
|
0.00%
0/4
|
2.9%
1/35 • Number of events 1
|
0.00%
0/33
|
|
General disorders
Multi-organ failure
|
0.00%
0/6
|
0.00%
0/4
|
2.9%
1/35 • Number of events 1
|
0.00%
0/33
|
|
General disorders
Pain
|
0.00%
0/6
|
0.00%
0/4
|
2.9%
1/35 • Number of events 1
|
0.00%
0/33
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/6
|
0.00%
0/4
|
2.9%
1/35 • Number of events 1
|
0.00%
0/33
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/6
|
0.00%
0/4
|
2.9%
1/35 • Number of events 1
|
0.00%
0/33
|
|
Infections and infestations
Prostate infection
|
0.00%
0/6
|
0.00%
0/4
|
2.9%
1/35 • Number of events 1
|
0.00%
0/33
|
|
Respiratory, thoracic and mediastinal disorders
Resp, thoracic & mediastinal disorder Other, spec
|
0.00%
0/6
|
0.00%
0/4
|
2.9%
1/35 • Number of events 1
|
0.00%
0/33
|
|
Infections and infestations
Sepsis
|
0.00%
0/6
|
0.00%
0/4
|
2.9%
1/35 • Number of events 1
|
0.00%
0/33
|
|
Infections and infestations
Sinusitis
|
0.00%
0/6
|
0.00%
0/4
|
2.9%
1/35 • Number of events 1
|
0.00%
0/33
|
|
Infections and infestations
Skin infection
|
0.00%
0/6
|
0.00%
0/4
|
2.9%
1/35 • Number of events 1
|
0.00%
0/33
|
|
Vascular disorders
Thromboembolic event
|
0.00%
0/6
|
0.00%
0/4
|
2.9%
1/35 • Number of events 1
|
0.00%
0/33
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/6
|
0.00%
0/4
|
0.00%
0/35
|
3.0%
1/33 • Number of events 1
|
|
Metabolism and nutrition disorders
Hyponatremia
|
0.00%
0/6
|
0.00%
0/4
|
0.00%
0/35
|
3.0%
1/33 • Number of events 1
|
|
Gastrointestinal disorders
Retroperitoneal hemorrhage
|
0.00%
0/6
|
0.00%
0/4
|
0.00%
0/35
|
3.0%
1/33 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Treatment related secondary malignancy
|
0.00%
0/6
|
0.00%
0/4
|
0.00%
0/35
|
3.0%
1/33 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain
|
0.00%
0/6
|
0.00%
0/4
|
0.00%
0/35
|
6.1%
2/33 • Number of events 2
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/6
|
0.00%
0/4
|
0.00%
0/35
|
3.0%
1/33 • Number of events 1
|
Other adverse events
| Measure |
RO4929097 10mg
n=6 participants at risk
RO4929097: 10mg PO QD, GDC-0449: 150 mg PO QD
|
RO4929097 15 mg
n=4 participants at risk
RO4929097: 15 mg PO QD, GDC-0449: 150 mg PO QD
|
ARM 1 - RO4929097: 15 mg PO QD
n=35 participants at risk
ARM 1 - RO4929097: 15 mg PO QD
|
ARM 2: GDC-0449 150 mg PO QD and RO4929097 15 mg PO QD
n=33 participants at risk
ARM 2: GDC-0449 150 mg PO QD and RO4929097 15 mg PO QD
|
|---|---|---|---|---|
|
Investigations
Activated partial thromboplastin time prolonged
|
16.7%
1/6 • Number of events 1
|
25.0%
1/4 • Number of events 2
|
0.00%
0/35
|
0.00%
0/33
|
|
Blood and lymphatic system disorders
Anemia
|
16.7%
1/6 • Number of events 12
|
75.0%
3/4 • Number of events 42
|
31.4%
11/35 • Number of events 56
|
24.2%
8/33 • Number of events 32
|
|
Eye disorders
Blurred vision
|
16.7%
1/6 • Number of events 1
|
0.00%
0/4
|
0.00%
0/35
|
0.00%
0/33
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
16.7%
1/6 • Number of events 1
|
0.00%
0/4
|
0.00%
0/35
|
0.00%
0/33
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
16.7%
1/6 • Number of events 1
|
50.0%
2/4 • Number of events 4
|
17.1%
6/35 • Number of events 34
|
15.2%
5/33 • Number of events 10
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
16.7%
1/6 • Number of events 11
|
75.0%
3/4 • Number of events 18
|
25.7%
9/35 • Number of events 21
|
12.1%
4/33 • Number of events 16
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
33.3%
2/6 • Number of events 13
|
25.0%
1/4 • Number of events 2
|
20.0%
7/35 • Number of events 13
|
3.0%
1/33 • Number of events 3
|
|
Metabolism and nutrition disorders
Hypokalemia
|
16.7%
1/6 • Number of events 2
|
25.0%
1/4 • Number of events 1
|
0.00%
0/35
|
3.0%
1/33 • Number of events 1
|
|
Metabolism and nutrition disorders
Hyponatremia
|
16.7%
1/6 • Number of events 1
|
25.0%
1/4 • Number of events 1
|
2.9%
1/35 • Number of events 1
|
0.00%
0/33
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
16.7%
1/6 • Number of events 4
|
75.0%
3/4 • Number of events 26
|
40.0%
14/35 • Number of events 50
|
36.4%
12/33 • Number of events 26
|
|
Investigations
Lymphocyte count decreased
|
33.3%
2/6 • Number of events 3
|
75.0%
3/4 • Number of events 12
|
17.1%
6/35 • Number of events 32
|
6.1%
2/33 • Number of events 5
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal & conn tissue disorder Other, spec
|
16.7%
1/6 • Number of events 3
|
0.00%
0/4
|
2.9%
1/35 • Number of events 2
|
6.1%
2/33 • Number of events 2
|
|
Investigations
Neutrophil count decreased
|
16.7%
1/6 • Number of events 2
|
25.0%
1/4 • Number of events 1
|
2.9%
1/35 • Number of events 1
|
6.1%
2/33 • Number of events 3
|
|
Investigations
White blood cell decreased
|
16.7%
1/6 • Number of events 1
|
25.0%
1/4 • Number of events 1
|
8.6%
3/35 • Number of events 3
|
3.0%
1/33 • Number of events 3
|
|
Metabolism and nutrition disorders
Anorexia
|
0.00%
0/6
|
25.0%
1/4 • Number of events 1
|
0.00%
0/35
|
0.00%
0/33
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/6
|
25.0%
1/4 • Number of events 1
|
0.00%
0/35
|
3.0%
1/33 • Number of events 1
|
|
General disorders
Fatigue
|
0.00%
0/6
|
50.0%
2/4 • Number of events 3
|
0.00%
0/35
|
6.1%
2/33 • Number of events 2
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/6
|
25.0%
1/4 • Number of events 1
|
0.00%
0/35
|
9.1%
3/33 • Number of events 4
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness upper limb
|
0.00%
0/6
|
25.0%
1/4 • Number of events 1
|
0.00%
0/35
|
0.00%
0/33
|
|
Respiratory, thoracic and mediastinal disorders
Pleuritic pain
|
0.00%
0/6
|
25.0%
1/4 • Number of events 1
|
0.00%
0/35
|
0.00%
0/33
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/6
|
0.00%
0/4
|
8.6%
3/35 • Number of events 6
|
6.1%
2/33 • Number of events 2
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/6
|
0.00%
0/4
|
5.7%
2/35 • Number of events 3
|
0.00%
0/33
|
|
Investigations
Alkaline phosphatase increased
|
0.00%
0/6
|
0.00%
0/4
|
8.6%
3/35 • Number of events 20
|
6.1%
2/33 • Number of events 6
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/6
|
0.00%
0/4
|
8.6%
3/35 • Number of events 7
|
3.0%
1/33 • Number of events 1
|
|
Investigations
CPK increased
|
0.00%
0/6
|
0.00%
0/4
|
0.00%
0/35
|
6.1%
2/33 • Number of events 3
|
|
Gastrointestinal disorders
Dysgeusia
|
0.00%
0/6
|
0.00%
0/4
|
0.00%
0/35
|
6.1%
2/33 • Number of events 2
|
Additional Information
Dr. Mrinal Gounder
Memorial Sloan Kettering Cancer Center
Phone: 646-888-4167
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60