Trial Outcomes & Findings for Onalespib, Dabrafenib, and Trametinib in Treating Patients With BRAF-Mutant Melanoma or Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery (NCT NCT02097225)
NCT ID: NCT02097225
Last Updated: 2024-10-16
Results Overview
Maximum tolerated dose is defined as the highest dose level at which 0 or 1 of six patients has experienced a dose limiting toxicity (DLT) within 28 days after start of treatment. Toxicities will be graded according to the Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0. Participant enrollment occurred from July 2015 to June 2018, spanning Dose Levels 1-4. * Dose Level 1 (starting dose): * Dabrafenib = 150 mg * Trametinib = 1 mg * Onalespib = 180 mg/m2 * Dose Level 2: * Dabrafenib = 150 mg * Trametinib = 2 mg * Onalespib = 180 mg/m2 * Dose Level 3: * Dabrafenib = 150 mg * Trametinib = 2 mg * Onalespib = 220 mg/m2 * Dose Level 4: * Dabrafenib = 150 mg * Trametinib = 2 mg * Onalespib = 260 mg/m2
Recruitment status
TERMINATED
Study phase
PHASE1
Target enrollment
22 participants
Primary outcome timeframe
28 days after start of treatment
Results posted on
2024-10-16
Participant Flow
Participant milestones
| Measure |
Dose Level -1: Dabrafenib = 75 mg, Trametinib = 1 mg, Onalespib = 180 mg/m2
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
There are four dose levels, plus a fallback dose. Dose escalation begins at dose level 1 (starting dose). Fallback dose level -1 is initiated if more than 1 of 6 subjects in dose level 1 (starting dose) develop DLTs.
\* Dose Level -1 (fallback dose):
* Dabrafenib = 75 mg
* Trametinib = 1 mg
* Onalespib = 180 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
Dose Level 1: Dabrafenib = 150 mg, Trametinib = 1 mg, Onalespib = 180 mg/m2
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
There are four dose levels, plus a fallback dose. Dose escalation begins at dose level 1 (starting dose).
\* Dose Level 1 (starting dose):
* Dabrafenib = 150 mg
* Trametinib = 1 mg
* Onalespib = 180 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
Dose Level 2: Dabrafenib = 150 mg, Trametinib = 2 mg, Onalespib = 180 mg/m2
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
There are four dose levels, plus a fallback dose. Dose escalation begins at dose level 1 (starting dose).
\* Dose Level 2:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 180 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
Dose Level 3: Dabrafenib = 150 mg, Trametinib = 2 mg, Onalespib = 220 mg/m2
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
There are four dose levels, plus a fallback dose. Dose escalation begins at dose level 1 (starting dose).
\* Dose Level 3:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 220 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
Dose Level 4: Dabrafenib = 150 mg, Trametinib = 2 mg, Onalespib = 260 mg/m2
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
There are four dose levels, plus a fallback dose. Dose escalation begins at dose level 1 (starting dose).
\* Dose Level 4:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 260 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
|---|---|---|---|---|---|
|
Dose Level 1
STARTED
|
0
|
3
|
0
|
0
|
0
|
|
Dose Level 1
COMPLETED
|
0
|
3
|
0
|
0
|
0
|
|
Dose Level 1
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
|
Dose Level 2
STARTED
|
0
|
0
|
4
|
0
|
0
|
|
Dose Level 2
COMPLETED
|
0
|
0
|
4
|
0
|
0
|
|
Dose Level 2
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
|
Dose Level 3
STARTED
|
0
|
0
|
0
|
6
|
0
|
|
Dose Level 3
COMPLETED
|
0
|
0
|
0
|
6
|
0
|
|
Dose Level 3
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
|
Dose Level 4
STARTED
|
0
|
0
|
0
|
0
|
9
|
|
Dose Level 4
COMPLETED
|
0
|
0
|
0
|
0
|
8
|
|
Dose Level 4
NOT COMPLETED
|
0
|
0
|
0
|
0
|
1
|
Reasons for withdrawal
| Measure |
Dose Level -1: Dabrafenib = 75 mg, Trametinib = 1 mg, Onalespib = 180 mg/m2
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
There are four dose levels, plus a fallback dose. Dose escalation begins at dose level 1 (starting dose). Fallback dose level -1 is initiated if more than 1 of 6 subjects in dose level 1 (starting dose) develop DLTs.
\* Dose Level -1 (fallback dose):
* Dabrafenib = 75 mg
* Trametinib = 1 mg
* Onalespib = 180 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
Dose Level 1: Dabrafenib = 150 mg, Trametinib = 1 mg, Onalespib = 180 mg/m2
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
There are four dose levels, plus a fallback dose. Dose escalation begins at dose level 1 (starting dose).
\* Dose Level 1 (starting dose):
* Dabrafenib = 150 mg
* Trametinib = 1 mg
* Onalespib = 180 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
Dose Level 2: Dabrafenib = 150 mg, Trametinib = 2 mg, Onalespib = 180 mg/m2
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
There are four dose levels, plus a fallback dose. Dose escalation begins at dose level 1 (starting dose).
\* Dose Level 2:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 180 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
Dose Level 3: Dabrafenib = 150 mg, Trametinib = 2 mg, Onalespib = 220 mg/m2
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
There are four dose levels, plus a fallback dose. Dose escalation begins at dose level 1 (starting dose).
\* Dose Level 3:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 220 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
Dose Level 4: Dabrafenib = 150 mg, Trametinib = 2 mg, Onalespib = 260 mg/m2
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
There are four dose levels, plus a fallback dose. Dose escalation begins at dose level 1 (starting dose).
\* Dose Level 4:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 260 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
|---|---|---|---|---|---|
|
Dose Level 4
Adverse Event
|
0
|
0
|
0
|
0
|
1
|
Baseline Characteristics
Onalespib, Dabrafenib, and Trametinib in Treating Patients With BRAF-Mutant Melanoma or Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery
Baseline characteristics by cohort
| Measure |
Dose Level -1: Dabrafenib = 75 mg, Trametinib = 1 mg, Onalespib = 180 mg/m2
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
There are four dose levels, plus a fallback dose. Dose escalation begins at dose level 1 (starting dose). Fallback dose level -1 is initiated if more than 1 of 6 subjects in dose level 1 (starting dose) develop DLTs.
\* Dose Level -1 (fallback dose):
* Dabrafenib = 75 mg
* Trametinib = 1 mg
* Onalespib = 180 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
Dose Level 1: Dabrafenib = 150 mg, Trametinib = 1 mg, Onalespib = 180 mg/m2
n=3 Participants
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
There are four dose levels, plus a fallback dose. Dose escalation begins at dose level 1 (starting dose).
\* Dose Level 1 (starting dose):
* Dabrafenib = 150 mg
* Trametinib = 1 mg
* Onalespib = 180 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
Dose Level 2: Dabrafenib = 150 mg, Trametinib = 2 mg, Onalespib = 180 mg/m2
n=4 Participants
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
There are four dose levels, plus a fallback dose. Dose escalation begins at dose level 1 (starting dose).
\* Dose Level 2:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 180 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
Dose Level 3: Dabrafenib = 150 mg, Trametinib = 2 mg, Onalespib = 220 mg/m2
n=6 Participants
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
There are four dose levels, plus a fallback dose. Dose escalation begins at dose level 1 (starting dose).
\* Dose Level 3:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 220 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
Dose Level 4: Dabrafenib = 150 mg, Trametinib = 2 mg, Onalespib = 260 mg/m2
n=9 Participants
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
There are four dose levels, plus a fallback dose. Dose escalation begins at dose level 1 (starting dose).
\* Dose Level 4:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 260 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
Total
n=22 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Continuous
|
—
|
51.0 years
n=7 Participants
|
66.5 years
n=5 Participants
|
54.0 years
n=4 Participants
|
58.0 years
n=21 Participants
|
57.5 years
n=10 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
5 Participants
n=21 Participants
|
13 Participants
n=10 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
9 Participants
n=10 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
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
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Asian
|
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
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
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
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Black or African American
|
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
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
8 Participants
n=21 Participants
|
21 Participants
n=10 Participants
|
|
Race (NIH/OMB)
More than one race
|
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
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
|
Performance Status
Score 0
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
7 Participants
n=10 Participants
|
|
Performance Status
Score 1
|
0 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
5 Participants
n=21 Participants
|
15 Participants
n=10 Participants
|
|
Months since diagnosis at time of study enrollment
|
—
|
7.8 months
n=7 Participants
|
19.2 months
n=5 Participants
|
68.8 months
n=4 Participants
|
18.9 months
n=21 Participants
|
19.7 months
n=10 Participants
|
|
Disease Histology
Adenocarcinoma of colon
|
—
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
12 Participants
n=10 Participants
|
|
Disease Histology
Metastatic melanoma
|
—
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
6 Participants
n=10 Participants
|
|
Disease Histology
Adenocarcinoma of lung
|
—
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
|
Disease Histology
Epithelioid sarcoma
|
—
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
|
Disease Histology
Anaplastic thyroid carcinoma
|
—
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
|
Disease Histology
Adenocarcinoma, Not otherwise specified
|
—
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
|
Prior Therapy Received
Chemotherapy, not otherwise specified
|
—
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
2 Participants
n=10 Participants
|
|
Prior Therapy Received
Chemotherapy, multiple agents systemic
|
—
|
3 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
8 Participants
n=21 Participants
|
19 Participants
n=10 Participants
|
|
Prior Therapy Received
Chemotherapy, single agent systemic
|
—
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
7 Participants
n=10 Participants
|
|
Prior Therapy Received
Chemotherapy, non-cytotoxic
|
—
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
|
Prior Therapy Received
Immunotherapy
|
—
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
8 Participants
n=10 Participants
|
|
Prior Therapy Received
Limited Radiation Therapy
|
—
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
5 Participants
n=10 Participants
|
|
Prior Therapy Received
Radiation Therapy, not otherwise specified
|
—
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
3 Participants
n=10 Participants
|
|
Prior Therapy Received
Surgery
|
—
|
3 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
9 Participants
n=21 Participants
|
22 Participants
n=10 Participants
|
|
Prior Therapy Received
Vaccine therapy
|
—
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
|
Prior Therapy Received
Prior therapy, not otherwise specified
|
—
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
PRIMARY outcome
Timeframe: 28 days after start of treatmentMaximum tolerated dose is defined as the highest dose level at which 0 or 1 of six patients has experienced a dose limiting toxicity (DLT) within 28 days after start of treatment. Toxicities will be graded according to the Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0. Participant enrollment occurred from July 2015 to June 2018, spanning Dose Levels 1-4. * Dose Level 1 (starting dose): * Dabrafenib = 150 mg * Trametinib = 1 mg * Onalespib = 180 mg/m2 * Dose Level 2: * Dabrafenib = 150 mg * Trametinib = 2 mg * Onalespib = 180 mg/m2 * Dose Level 3: * Dabrafenib = 150 mg * Trametinib = 2 mg * Onalespib = 220 mg/m2 * Dose Level 4: * Dabrafenib = 150 mg * Trametinib = 2 mg * Onalespib = 260 mg/m2
Outcome measures
| Measure |
Treatment (Dabrafenib, Trametinib, Onalespib)
n=21 Participants
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Four dose levels, plus a fallback dose, are summarized in the table below. Dose escalation begins at dose level 1 (starting dose).
* Dose Level -1:
* Dabrafenib = 75 mg
* Trametinib = 1 mg
* Onalespib = 180 mg/m2
* Dose Level 1 (starting dose):
* Dabrafenib = 150 mg
* Trametinib = 1 mg
* Onalespib = 180 mg/m2
* Dose Level 2:
* Dabrafenib = 75 mg
* Trametinib = 1 mg
* Onalespib = 180 mg/m2
* Dose Level 3:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 220 mg/m2
* Dose Level 4:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 260 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
Dose Level 2: Dabrafenib = 150 mg, Trametinib = 2 mg, Onalespib = 180 mg/m2
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
There are four dose levels, plus a fallback dose. Dose escalation begins at dose level 1 (starting dose).
\* Dose Level 2:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 180 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
Dose Level 3: Dabrafenib = 150 mg, Trametinib = 2 mg, Onalespib = 220 mg/m2
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
There are four dose levels, plus a fallback dose. Dose escalation begins at dose level 1 (starting dose).
\* Dose Level 3:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 220 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
Dose Level 4: Dabrafenib = 150 mg, Trametinib = 2 mg, Onalespib = 260 mg/m2
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
There are four dose levels, plus a fallback dose. Dose escalation begins at dose level 1 (starting dose).
\* Dose Level 4:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 260 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
|---|---|---|---|---|
|
Maximum Tolerated Dose of Dabrafenib
|
150 mg
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: 28 days after start of treatmentMaximum tolerated dose is defined as the highest dose level at which 0 or 1 of six patients has experienced a dose limiting toxicity (DLT) within 28 days after start of treatment. Toxicities will be graded according to the Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0. Participant enrollment occurred from July 2015 to June 2018, spanning Dose Levels 1-4. * Dose Level 1 (starting dose): * Dabrafenib = 150 mg * Trametinib = 1 mg * Onalespib = 180 mg/m2 * Dose Level 2: * Dabrafenib = 150 mg * Trametinib = 2 mg * Onalespib = 180 mg/m2 * Dose Level 3: * Dabrafenib = 150 mg * Trametinib = 2 mg * Onalespib = 220 mg/m2 * Dose Level 4: * Dabrafenib = 150 mg * Trametinib = 2 mg * Onalespib = 260 mg/m2
Outcome measures
| Measure |
Treatment (Dabrafenib, Trametinib, Onalespib)
n=18 Participants
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Four dose levels, plus a fallback dose, are summarized in the table below. Dose escalation begins at dose level 1 (starting dose).
* Dose Level -1:
* Dabrafenib = 75 mg
* Trametinib = 1 mg
* Onalespib = 180 mg/m2
* Dose Level 1 (starting dose):
* Dabrafenib = 150 mg
* Trametinib = 1 mg
* Onalespib = 180 mg/m2
* Dose Level 2:
* Dabrafenib = 75 mg
* Trametinib = 1 mg
* Onalespib = 180 mg/m2
* Dose Level 3:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 220 mg/m2
* Dose Level 4:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 260 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
Dose Level 2: Dabrafenib = 150 mg, Trametinib = 2 mg, Onalespib = 180 mg/m2
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
There are four dose levels, plus a fallback dose. Dose escalation begins at dose level 1 (starting dose).
\* Dose Level 2:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 180 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
Dose Level 3: Dabrafenib = 150 mg, Trametinib = 2 mg, Onalespib = 220 mg/m2
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
There are four dose levels, plus a fallback dose. Dose escalation begins at dose level 1 (starting dose).
\* Dose Level 3:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 220 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
Dose Level 4: Dabrafenib = 150 mg, Trametinib = 2 mg, Onalespib = 260 mg/m2
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
There are four dose levels, plus a fallback dose. Dose escalation begins at dose level 1 (starting dose).
\* Dose Level 4:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 260 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
|---|---|---|---|---|
|
Maximum Tolerated Dose of Trametinib
|
2 mg
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: 28 days after start of treatmentMaximum tolerated dose is defined as the highest dose level at which 0 or 1 of six patients has experienced a dose limiting toxicity (DLT) within 28 days after start of treatment. Toxicities will be graded according to the Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0. Participant enrollment occurred from July 2015 to June 2018, spanning Dose Levels 1-4. * Dose Level 1 (starting dose): * Dabrafenib = 150 mg * Trametinib = 1 mg * Onalespib = 180 mg/m2 * Dose Level 2: * Dabrafenib = 150 mg * Trametinib = 2 mg * Onalespib = 180 mg/m2 * Dose Level 3: * Dabrafenib = 150 mg * Trametinib = 2 mg * Onalespib = 220 mg/m2 * Dose Level 4: * Dabrafenib = 150 mg * Trametinib = 2 mg * Onalespib = 260 mg/m2
Outcome measures
| Measure |
Treatment (Dabrafenib, Trametinib, Onalespib)
n=8 Participants
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Four dose levels, plus a fallback dose, are summarized in the table below. Dose escalation begins at dose level 1 (starting dose).
* Dose Level -1:
* Dabrafenib = 75 mg
* Trametinib = 1 mg
* Onalespib = 180 mg/m2
* Dose Level 1 (starting dose):
* Dabrafenib = 150 mg
* Trametinib = 1 mg
* Onalespib = 180 mg/m2
* Dose Level 2:
* Dabrafenib = 75 mg
* Trametinib = 1 mg
* Onalespib = 180 mg/m2
* Dose Level 3:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 220 mg/m2
* Dose Level 4:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 260 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
Dose Level 2: Dabrafenib = 150 mg, Trametinib = 2 mg, Onalespib = 180 mg/m2
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
There are four dose levels, plus a fallback dose. Dose escalation begins at dose level 1 (starting dose).
\* Dose Level 2:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 180 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
Dose Level 3: Dabrafenib = 150 mg, Trametinib = 2 mg, Onalespib = 220 mg/m2
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
There are four dose levels, plus a fallback dose. Dose escalation begins at dose level 1 (starting dose).
\* Dose Level 3:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 220 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
Dose Level 4: Dabrafenib = 150 mg, Trametinib = 2 mg, Onalespib = 260 mg/m2
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
There are four dose levels, plus a fallback dose. Dose escalation begins at dose level 1 (starting dose).
\* Dose Level 4:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 260 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
|---|---|---|---|---|
|
Maximum Tolerated Dose of Onalespib
|
260 mg/m2
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: 28 days after start of treatment (1 cycle)Dose limiting toxicities (DLTs) are at least possibly related to study treatment and graded according to the Common Toxicity Criteria for Adverse Events (CTCAE) v5.0: * any grade 4 toxicity * grade 3 (or grade 2 intolerable) non-hematologic toxicity (including fatigue lasting \>1 week or that requires hospitalization) * grade 3 or higher hematologic toxicity with complications (e.g., thrombocytopenia with bleeding, neutropenia with fever) * toxicity that lead to missing a dose of onalespib or \>25% of dabrafenib/trametinib in the first cycle The following grade 3 toxicities are not considered DLTs: * cutaneous squamous cell carcinoma or keratoacanthoma * nausea, vomiting, or diarrhea persisting \</= 72 hours with maximum supportive care * electrolyte events that resolve with replacement within 24 hours * any grade lymphopenia * lab abnormalities that return to baseline within 7 days: elevated bilirubin, AST, ALT, cholesterol, amylase, lipase, creatinine, hypertriglyceridemia
Outcome measures
| Measure |
Treatment (Dabrafenib, Trametinib, Onalespib)
n=3 Participants
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Four dose levels, plus a fallback dose, are summarized in the table below. Dose escalation begins at dose level 1 (starting dose).
* Dose Level -1:
* Dabrafenib = 75 mg
* Trametinib = 1 mg
* Onalespib = 180 mg/m2
* Dose Level 1 (starting dose):
* Dabrafenib = 150 mg
* Trametinib = 1 mg
* Onalespib = 180 mg/m2
* Dose Level 2:
* Dabrafenib = 75 mg
* Trametinib = 1 mg
* Onalespib = 180 mg/m2
* Dose Level 3:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 220 mg/m2
* Dose Level 4:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 260 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
Dose Level 2: Dabrafenib = 150 mg, Trametinib = 2 mg, Onalespib = 180 mg/m2
n=4 Participants
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
There are four dose levels, plus a fallback dose. Dose escalation begins at dose level 1 (starting dose).
\* Dose Level 2:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 180 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
Dose Level 3: Dabrafenib = 150 mg, Trametinib = 2 mg, Onalespib = 220 mg/m2
n=6 Participants
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
There are four dose levels, plus a fallback dose. Dose escalation begins at dose level 1 (starting dose).
\* Dose Level 3:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 220 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
Dose Level 4: Dabrafenib = 150 mg, Trametinib = 2 mg, Onalespib = 260 mg/m2
n=8 Participants
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
There are four dose levels, plus a fallback dose. Dose escalation begins at dose level 1 (starting dose).
\* Dose Level 4:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 260 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
|---|---|---|---|---|
|
Number of Dose Limiting Toxicities While Determining Maximum Tolerated Dose
Grade 3 toxicity
|
0 dose limiting toxicities
|
0 dose limiting toxicities
|
5 dose limiting toxicities
|
1 dose limiting toxicities
|
|
Number of Dose Limiting Toxicities While Determining Maximum Tolerated Dose
Grade 4 toxicity
|
0 dose limiting toxicities
|
0 dose limiting toxicities
|
0 dose limiting toxicities
|
0 dose limiting toxicities
|
SECONDARY outcome
Timeframe: up to 9 monthsObjective response rate is defined as the number of participants with complete response or partial response as their best response to therapy assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1. * Complete response (CR) = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. * Partial response (PR) = At least a 30% decrease in the sum of longest diameters of target lesions, taking as reference the baseline sum diameters.
Outcome measures
| Measure |
Treatment (Dabrafenib, Trametinib, Onalespib)
n=3 Participants
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Four dose levels, plus a fallback dose, are summarized in the table below. Dose escalation begins at dose level 1 (starting dose).
* Dose Level -1:
* Dabrafenib = 75 mg
* Trametinib = 1 mg
* Onalespib = 180 mg/m2
* Dose Level 1 (starting dose):
* Dabrafenib = 150 mg
* Trametinib = 1 mg
* Onalespib = 180 mg/m2
* Dose Level 2:
* Dabrafenib = 75 mg
* Trametinib = 1 mg
* Onalespib = 180 mg/m2
* Dose Level 3:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 220 mg/m2
* Dose Level 4:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 260 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
Dose Level 2: Dabrafenib = 150 mg, Trametinib = 2 mg, Onalespib = 180 mg/m2
n=4 Participants
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
There are four dose levels, plus a fallback dose. Dose escalation begins at dose level 1 (starting dose).
\* Dose Level 2:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 180 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
Dose Level 3: Dabrafenib = 150 mg, Trametinib = 2 mg, Onalespib = 220 mg/m2
n=6 Participants
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
There are four dose levels, plus a fallback dose. Dose escalation begins at dose level 1 (starting dose).
\* Dose Level 3:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 220 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
Dose Level 4: Dabrafenib = 150 mg, Trametinib = 2 mg, Onalespib = 260 mg/m2
n=8 Participants
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
There are four dose levels, plus a fallback dose. Dose escalation begins at dose level 1 (starting dose).
\* Dose Level 4:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 260 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
|---|---|---|---|---|
|
Objective Response Rate
Complete response (CR)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Objective Response Rate
Partial response (PR)
|
0 Participants
|
0 Participants
|
2 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: up to 9 monthsProgression-free survival (PFS) is defined as the duration of time from start of treatment to time of progressive disease assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1, or death, whichever occurs first. Progressive disease (PD) = At least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the baseline sum of diameters. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progressions.
Outcome measures
| Measure |
Treatment (Dabrafenib, Trametinib, Onalespib)
n=3 Participants
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Four dose levels, plus a fallback dose, are summarized in the table below. Dose escalation begins at dose level 1 (starting dose).
* Dose Level -1:
* Dabrafenib = 75 mg
* Trametinib = 1 mg
* Onalespib = 180 mg/m2
* Dose Level 1 (starting dose):
* Dabrafenib = 150 mg
* Trametinib = 1 mg
* Onalespib = 180 mg/m2
* Dose Level 2:
* Dabrafenib = 75 mg
* Trametinib = 1 mg
* Onalespib = 180 mg/m2
* Dose Level 3:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 220 mg/m2
* Dose Level 4:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 260 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
Dose Level 2: Dabrafenib = 150 mg, Trametinib = 2 mg, Onalespib = 180 mg/m2
n=4 Participants
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
There are four dose levels, plus a fallback dose. Dose escalation begins at dose level 1 (starting dose).
\* Dose Level 2:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 180 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
Dose Level 3: Dabrafenib = 150 mg, Trametinib = 2 mg, Onalespib = 220 mg/m2
n=6 Participants
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
There are four dose levels, plus a fallback dose. Dose escalation begins at dose level 1 (starting dose).
\* Dose Level 3:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 220 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
Dose Level 4: Dabrafenib = 150 mg, Trametinib = 2 mg, Onalespib = 260 mg/m2
n=8 Participants
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
There are four dose levels, plus a fallback dose. Dose escalation begins at dose level 1 (starting dose).
\* Dose Level 4:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 260 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
|---|---|---|---|---|
|
Progression-free Survival
|
1.6 months
Interval 0.9 to 1.7
|
1.5 months
Interval 0.6 to 3.6
|
3.9 months
Interval 1.8 to 9.2
|
2.7 months
Interval 1.5 to 3.8
|
SECONDARY outcome
Timeframe: 6 monthsProgression-free survival (PFS) is defined as the duration of time from start of treatment to time of progressive disease assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1, or death, whichever occurs first. PFS at 6 months will report the number of participants without progression at 6 months after starting treatment. Progressive disease (PD) = At least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the baseline sum of diameters. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progressions.
Outcome measures
| Measure |
Treatment (Dabrafenib, Trametinib, Onalespib)
n=3 Participants
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Four dose levels, plus a fallback dose, are summarized in the table below. Dose escalation begins at dose level 1 (starting dose).
* Dose Level -1:
* Dabrafenib = 75 mg
* Trametinib = 1 mg
* Onalespib = 180 mg/m2
* Dose Level 1 (starting dose):
* Dabrafenib = 150 mg
* Trametinib = 1 mg
* Onalespib = 180 mg/m2
* Dose Level 2:
* Dabrafenib = 75 mg
* Trametinib = 1 mg
* Onalespib = 180 mg/m2
* Dose Level 3:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 220 mg/m2
* Dose Level 4:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 260 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
Dose Level 2: Dabrafenib = 150 mg, Trametinib = 2 mg, Onalespib = 180 mg/m2
n=4 Participants
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
There are four dose levels, plus a fallback dose. Dose escalation begins at dose level 1 (starting dose).
\* Dose Level 2:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 180 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
Dose Level 3: Dabrafenib = 150 mg, Trametinib = 2 mg, Onalespib = 220 mg/m2
n=6 Participants
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
There are four dose levels, plus a fallback dose. Dose escalation begins at dose level 1 (starting dose).
\* Dose Level 3:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 220 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
Dose Level 4: Dabrafenib = 150 mg, Trametinib = 2 mg, Onalespib = 260 mg/m2
n=8 Participants
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
There are four dose levels, plus a fallback dose. Dose escalation begins at dose level 1 (starting dose).
\* Dose Level 4:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 260 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
|---|---|---|---|---|
|
Progression-free Survival at 6 Months
|
0 Participants
|
0 Participants
|
2 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: 1 yearOverall survival (OS) is defined as the time from start of treatment to death from any cause. OS at 1 year will report the number of participants alive at 1 year after starting treatment.
Outcome measures
| Measure |
Treatment (Dabrafenib, Trametinib, Onalespib)
n=3 Participants
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Four dose levels, plus a fallback dose, are summarized in the table below. Dose escalation begins at dose level 1 (starting dose).
* Dose Level -1:
* Dabrafenib = 75 mg
* Trametinib = 1 mg
* Onalespib = 180 mg/m2
* Dose Level 1 (starting dose):
* Dabrafenib = 150 mg
* Trametinib = 1 mg
* Onalespib = 180 mg/m2
* Dose Level 2:
* Dabrafenib = 75 mg
* Trametinib = 1 mg
* Onalespib = 180 mg/m2
* Dose Level 3:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 220 mg/m2
* Dose Level 4:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 260 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
Dose Level 2: Dabrafenib = 150 mg, Trametinib = 2 mg, Onalespib = 180 mg/m2
n=4 Participants
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
There are four dose levels, plus a fallback dose. Dose escalation begins at dose level 1 (starting dose).
\* Dose Level 2:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 180 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
Dose Level 3: Dabrafenib = 150 mg, Trametinib = 2 mg, Onalespib = 220 mg/m2
n=6 Participants
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
There are four dose levels, plus a fallback dose. Dose escalation begins at dose level 1 (starting dose).
\* Dose Level 3:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 220 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
Dose Level 4: Dabrafenib = 150 mg, Trametinib = 2 mg, Onalespib = 260 mg/m2
n=8 Participants
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
There are four dose levels, plus a fallback dose. Dose escalation begins at dose level 1 (starting dose).
\* Dose Level 4:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 260 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
|---|---|---|---|---|
|
Overall Survival at 1 Year
|
0 Participants
|
0 Participants
|
1 Participants
|
3 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 1 hour immediately after Cycle 1, Day 1 infusionPopulation: There were 18 out of 21 total evaluable patients had blood samples analyzed on Cycle 1 Day 1.
Pharmacokinetics (PKs) represents the absorption, distribution, metabolism, and elimination of study drugs from the body. PKs for this study are reported a Area Under the Curve (AUC), which is estimated using the trapezoidal rule based on the average drug concentrations in blood samples, specifically blood plasma, at 1 hour immediately after study drug infusion. AUC gives insight into the extent of exposure to a drug and its clearance rate from the body.
Outcome measures
| Measure |
Treatment (Dabrafenib, Trametinib, Onalespib)
n=3 Participants
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Four dose levels, plus a fallback dose, are summarized in the table below. Dose escalation begins at dose level 1 (starting dose).
* Dose Level -1:
* Dabrafenib = 75 mg
* Trametinib = 1 mg
* Onalespib = 180 mg/m2
* Dose Level 1 (starting dose):
* Dabrafenib = 150 mg
* Trametinib = 1 mg
* Onalespib = 180 mg/m2
* Dose Level 2:
* Dabrafenib = 75 mg
* Trametinib = 1 mg
* Onalespib = 180 mg/m2
* Dose Level 3:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 220 mg/m2
* Dose Level 4:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 260 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
Dose Level 2: Dabrafenib = 150 mg, Trametinib = 2 mg, Onalespib = 180 mg/m2
n=3 Participants
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
There are four dose levels, plus a fallback dose. Dose escalation begins at dose level 1 (starting dose).
\* Dose Level 2:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 180 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
Dose Level 3: Dabrafenib = 150 mg, Trametinib = 2 mg, Onalespib = 220 mg/m2
n=6 Participants
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
There are four dose levels, plus a fallback dose. Dose escalation begins at dose level 1 (starting dose).
\* Dose Level 3:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 220 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
Dose Level 4: Dabrafenib = 150 mg, Trametinib = 2 mg, Onalespib = 260 mg/m2
n=6 Participants
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
There are four dose levels, plus a fallback dose. Dose escalation begins at dose level 1 (starting dose).
\* Dose Level 4:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 260 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
|---|---|---|---|---|
|
Pharmacokinetics of Dabrafenib, Trametinib, and Onalespib Combination
|
357 ng*hr/mL
Interval 182.0 to 374.0
|
344 ng*hr/mL
Interval 210.0 to 348.0
|
395 ng*hr/mL
Interval 312.0 to 502.0
|
448 ng*hr/mL
Interval 362.0 to 2310.0
|
Adverse Events
Dose Level 1: Dabrafenib = 150 mg, Trametinib = 1 mg, Onalespib = 180 mg/m2
Serious events: 1 serious events
Other events: 3 other events
Deaths: 3 deaths
Dose Level 2: Dabrafenib = 150 mg, Trametinib = 2 mg, Onalespib = 180 mg/m2
Serious events: 1 serious events
Other events: 4 other events
Deaths: 4 deaths
Dose Level 3: Dabrafenib = 150 mg, Trametinib = 2 mg, Onalespib = 220 mg/m2
Serious events: 0 serious events
Other events: 6 other events
Deaths: 6 deaths
Dose Level 4: Dabrafenib = 150 mg, Trametinib = 2 mg, Onalespib = 260 mg/m2
Serious events: 2 serious events
Other events: 8 other events
Deaths: 7 deaths
Serious adverse events
| Measure |
Dose Level 1: Dabrafenib = 150 mg, Trametinib = 1 mg, Onalespib = 180 mg/m2
n=3 participants at risk
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Four dose levels, plus a fallback dose, are summarized in the table below. Dose escalation begins at dose level 1 (starting dose).
\*Dose Level 1 (starting dose):
* Dabrafenib = 150 mg
* Trametinib = 1 mg
* Onalespib = 180 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
Dose Level 2: Dabrafenib = 150 mg, Trametinib = 2 mg, Onalespib = 180 mg/m2
n=4 participants at risk
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
There are four dose levels, plus a fallback dose. Dose escalation begins at dose level 1 (starting dose).
\* Dose Level 2:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 180 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
Dose Level 3: Dabrafenib = 150 mg, Trametinib = 2 mg, Onalespib = 220 mg/m2
n=6 participants at risk
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
There are four dose levels, plus a fallback dose. Dose escalation begins at dose level 1 (starting dose).
\* Dose Level 3:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 220 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
Dose Level 4: Dabrafenib = 150 mg, Trametinib = 2 mg, Onalespib = 260 mg/m2
n=8 participants at risk
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
There are four dose levels, plus a fallback dose. Dose escalation begins at dose level 1 (starting dose).
\* Dose Level 4:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 260 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
|---|---|---|---|---|
|
Investigations
Investigations - Other, specify
|
33.3%
1/3 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
25.0%
1/4 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/6 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
25.0%
2/8 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/3 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
25.0%
1/4 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/6 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/8 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
|
Vascular disorders
Hypotension
|
0.00%
0/3 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/4 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/6 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
12.5%
1/8 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
|
Infections and infestations
Sepsis
|
0.00%
0/3 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/4 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/6 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
12.5%
1/8 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
|
Infections and infestations
Infections and infestations Other, specify
|
0.00%
0/3 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/4 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/6 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
12.5%
1/8 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
0.00%
0/3 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/4 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/6 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
12.5%
1/8 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
Other adverse events
| Measure |
Dose Level 1: Dabrafenib = 150 mg, Trametinib = 1 mg, Onalespib = 180 mg/m2
n=3 participants at risk
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Four dose levels, plus a fallback dose, are summarized in the table below. Dose escalation begins at dose level 1 (starting dose).
\*Dose Level 1 (starting dose):
* Dabrafenib = 150 mg
* Trametinib = 1 mg
* Onalespib = 180 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
Dose Level 2: Dabrafenib = 150 mg, Trametinib = 2 mg, Onalespib = 180 mg/m2
n=4 participants at risk
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
There are four dose levels, plus a fallback dose. Dose escalation begins at dose level 1 (starting dose).
\* Dose Level 2:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 180 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
Dose Level 3: Dabrafenib = 150 mg, Trametinib = 2 mg, Onalespib = 220 mg/m2
n=6 participants at risk
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
There are four dose levels, plus a fallback dose. Dose escalation begins at dose level 1 (starting dose).
\* Dose Level 3:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 220 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
Dose Level 4: Dabrafenib = 150 mg, Trametinib = 2 mg, Onalespib = 260 mg/m2
n=8 participants at risk
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28, and onalespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
There are four dose levels, plus a fallback dose. Dose escalation begins at dose level 1 (starting dose).
\* Dose Level 4:
* Dabrafenib = 150 mg
* Trametinib = 2 mg
* Onalespib = 260 mg/m2
Dabrafenib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Onalespib: Given IV
Pharmacological Study: Correlative studies
Trametinib: Given PO
|
|---|---|---|---|---|
|
Vascular disorders
Thromboembolic Event
|
33.3%
1/3 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
25.0%
1/4 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/6 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/8 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
|
Gastrointestinal disorders
Abdominal Pain
|
0.00%
0/3 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
50.0%
2/4 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/6 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/8 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/3 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
25.0%
1/4 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/6 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/8 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.00%
0/3 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
25.0%
1/4 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/6 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/8 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
|
General disorders
Fatigue
|
0.00%
0/3 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/4 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
33.3%
2/6 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
12.5%
1/8 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
|
Gastrointestinal disorders
Lower Gastrointestinal Hemorrhage
|
0.00%
0/3 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/4 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
16.7%
1/6 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/8 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
|
Metabolism and nutrition disorders
Hyponatremia
|
0.00%
0/3 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
50.0%
2/4 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
33.3%
2/6 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
12.5%
1/8 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
|
Musculoskeletal and connective tissue disorders
Generalized Muscle Weakness
|
33.3%
1/3 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/4 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/6 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/8 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
|
Nervous system disorders
Depressed level of consciousness
|
0.00%
0/3 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/4 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/6 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
12.5%
1/8 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
|
General disorders
Gait Disturbance
|
0.00%
0/3 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/4 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/6 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
12.5%
1/8 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
0.00%
0/3 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/4 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/6 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
12.5%
1/8 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/3 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/4 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/6 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
12.5%
1/8 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/3 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/4 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/6 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
12.5%
1/8 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
|
Vascular disorders
Hypotension
|
0.00%
0/3 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
25.0%
1/4 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/6 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/8 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
|
General disorders
Fever
|
0.00%
0/3 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/4 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/6 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
12.5%
1/8 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
|
Investigations
Blood bilirubin increased
|
33.3%
1/3 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/4 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/6 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/8 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
|
Nervous system disorders
Neuralgia
|
33.3%
1/3 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/4 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/6 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/8 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
|
General disorders
Pain, unspecified
|
33.3%
1/3 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/4 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/6 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/8 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
|
Nervous system disorders
Somnolence
|
33.3%
1/3 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/4 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/6 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/8 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
|
Investigations
Alkaline Phosphatase Increased
|
0.00%
0/3 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
25.0%
1/4 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/6 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/8 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/3 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
25.0%
1/4 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/6 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/8 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
|
Blood and lymphatic system disorders
Anemia
|
0.00%
0/3 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/4 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
33.3%
2/6 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/8 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
|
Investigations
Neutrophil Count Decreased
|
0.00%
0/3 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/4 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
16.7%
1/6 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/8 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
|
Investigations
Platelet count decreased
|
0.00%
0/3 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/4 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
16.7%
1/6 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/8 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
|
Investigations
White Blood Cell Decreased
|
0.00%
0/3 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/4 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
33.3%
2/6 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/8 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
0.00%
0/3 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/4 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
33.3%
2/6 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
12.5%
1/8 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
|
Investigations
Alanine Aminotransferase Increased
|
0.00%
0/3 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/4 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/6 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
12.5%
1/8 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
0.00%
0/3 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/4 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/6 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
12.5%
1/8 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
|
Musculoskeletal and connective tissue disorders
Muscle Weakness Lower Limb
|
0.00%
0/3 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/4 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/6 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
12.5%
1/8 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
|
Gastrointestinal disorders
Colonic Obstruction
|
0.00%
0/3 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/4 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
16.7%
1/6 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/8 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
|
Vascular disorders
Hypertension
|
0.00%
0/3 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/4 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
0.00%
0/6 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
12.5%
1/8 • Up to approximately 4.5 years, starting from the day 1 of dosing throughout post-treatment follow-up.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60