Onalespib, Dabrafenib, and Trametinib in Treating Patients With BRAF-Mutant Melanoma or Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery
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|ClinicalTrials.gov Identifier: NCT02097225|
Recruitment Status : Active, not recruiting
First Posted : March 27, 2014
Last Update Posted : February 17, 2021
|Condition or disease||Intervention/treatment||Phase|
|BRAF V600E Mutation Present BRAF V600K Mutation Present Metastatic Malignant Solid Neoplasm Metastatic Melanoma Stage III Cutaneous Melanoma AJCC v7 Stage IIIA Cutaneous Melanoma AJCC v7 Stage IIIB Cutaneous Melanoma AJCC v7 Stage IIIC Cutaneous Melanoma AJCC v7 Stage IV Cutaneous Melanoma AJCC v6 and v7 Unresectable Solid Neoplasm||Drug: Dabrafenib Other: Laboratory Biomarker Analysis Drug: Onalespib Other: Pharmacological Study Drug: Trametinib||Phase 1|
I. To determine the maximum tolerated dose (MTD), toxicity, and safety profile of onalespib (AT13387) given weekly in combination with dabrafenib and trametinib in patients with BRAF-mutant metastatic or unresectable solid tumors.
I. To obtain preliminary estimates of the objective response rate (ORR) and progression-free survival (PFS) and document the 6-month PFS and 1-year overall survival (OS) of patients with BRAF-mutant metastatic or unresectable melanoma treated with AT13387 given weekly in combination with dabrafenib and trametinib.
II. To describe the pharmacokinetics of treatment with dabrafenib, trametinib, and AT13387.
OUTLINE: This is a dose-escalation study of onalespib.
Patients receive dabrafenib orally (PO) twice daily (BID), trametinib PO once daily (QD) on days 1-28, and onalespib intravenously (IV) over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 28 days and every 6 months for up to 2 years.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||22 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Study of AT13387 in Combination With Dabrafenib and Trametinib in Patients With BRAF-Mutant Melanoma and Other Solid Tumors|
|Actual Study Start Date :||May 29, 2014|
|Actual Primary Completion Date :||March 31, 2019|
Experimental: Treatment (dabrafenib, trametinib, onalespib)
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.
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
- Maximum tolerated dose of onalespib in combination with dabrafenib and trametinib, defined as the highest dose level at which 0 or 1 of six patients has experienced a dose limiting toxicity [ Time Frame: 28 days ]Toxicities will be graded according to the National Cancer Institute Common Toxicity Criteria for Adverse Events version 5.0. Toxicity rates will be summarized with a 90% exact binomial confidence interval.
- Objective response rate, defined as the proportion of patients with complete or partial response as their best response to therapy assessed according to Response Evaluation Criteria in Solid Tumors version 1.1 [ Time Frame: The date of first dose of trial therapy and the date of objectively documented disease progression or cessation of trial therapy, whichever occurs first, assessed up to 28 days after end of treatment ]The response rate will be presented as a point estimate with a 90% exact binomial confidence interval.
- Progression-free survival [ Time Frame: Time from start of treatment to time of progression or death, whichever occurs first, assessed up to 28 days after end of treatment ]The distribution of progression-free survival will be summarized using the product-limit method of Kaplan-Meier.
- Progression-free survival [ Time Frame: Time from start of treatment to time of progression or death, whichever occurs first, assessed at 6 months ]Median times for each endpoint will be presented with two-sided, 90% confidence intervals estimated using log(-log[survival]) methodology. Kaplan-Meier estimates of 6-month progression-free survival will also be presented with two-sided, 90% confidence intervals.
- Overall survival [ Time Frame: 1 year ]The distribution of overall survival will be summarized using the product-limit method of Kaplan-Meier. Kaplan-Meier estimates of 1-year overall survival will also be presented with two-sided, 90% confidence intervals.
- Disease-free survival [ Time Frame: 1 year ]The one-year disease-free survival after treatment will be estimated using the product-limit methods of Kaplan-Meier, and presented with 90% confidence intervals.
- Pharmacokinetic parameters (maximal plasma or serum concentration, area under the curve to the last collection point, area under the curve for dose interval, and time of maximal concentration) [ Time Frame: Course 1, days 1 and 15 (pre-dose, 1, 2, 4, 6, 8, 24 hour post-dose) and day 1 in courses 2, 4, 8, and 12 (pre-dose) ]Descriptive statistics including mean, standard deviation, coefficient of variation, geometric mean, median, minimum and maximum will be computed for each pharmacokinetic variable; descriptive statistics for natural-log transformed pharmacokinetic variables will also be provided.
- Changes in the expression of the key signaling proteins [ Time Frame: Baseline to 7 days (1 week) ]Will be performed to assess how changes in the expression of the key signaling proteins relate to patient response.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02097225
|United States, Massachusetts|
|Massachusetts General Hospital Cancer Center|
|Boston, Massachusetts, United States, 02114|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02215|
|Principal Investigator:||Ryan J Sullivan||Massachusetts General Hospital|