Lapatinib and Bortezomib in Patients With Advanced Malignancies
This study is for patients with an advanced type of cancer for which no curative treatment exists.
The purpose of this study is to test the safety and efficacy of the combination of the study drugs, lapatinib and bortezomib. Lapatinib is a drug that targets two proteins important for the growth of cancer cells known as HER1 (EGFR) and HER2. By inhibiting these proteins, lapatinib can inhibit cancer cell growth and even lead to their death. Lapatinib is an oral pill given by mouth once every day. Lapatinib is approved by the FDA for patients with breast cancer.
Bortezomib is a drug that targets a part of cancer cells known as the proteosome. By inhibiting the proteosome, bortezomib can inhibit cancer cell growth and even lead to their death. Bortezomib is given intravenously, once a week, 2 out of every 3 weeks. Bortezomib is approved by the FDA for patients with multiple myeloma and mantle cell lymphoma.
This research is being done because it is not known if the combination of lapatinib and bortezomib will work better than lapatinib or bortezomib alone, although in the lab and in animal studies the combination of the two drugs was much more effective than either drug alone.
As part of this study biopsies will be taken of patients' tumors before any treatment, after starting lapatinib alone, and after receiving both lapatinib and bortezomib. Investigators want to study what markers inside tumors may relate to how well these two medications work. These biopsies are required as part of the study.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of the HER1, HER2 Dual Kinase Inhibitor, Lapatinib Plus the Proteosomal Inhibitor Bortezomib in Patients With Advanced Malignancies|
- Maximum tolerated dose [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]The highest dose at which </= 1 out of 6 subjects has a dose-limiting toxicity
- toxicity [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]Adverse events seen during the trial graded using CTCAE version 4
- Response rate [ Time Frame: 18 months ] [ Designated as safety issue: No ]complete response and partial response measured by RECIST 1.1
- Disease control rate [ Time Frame: 2 months ] [ Designated as safety issue: No ]stable disease after two cycles+ partial response + complete response as determined by RECIST 1.1 criteria
- Pharmacodynamics [ Time Frame: pre-treatment, after 1 week of therapy and adter 3 weeks of therapy ] [ Designated as safety issue: No ]To assess changes in the following in serial tumor samples: EGFR, HER2, HER3, AKT, Actin, ERK, GSK3a-beta, IGF-1R, MEK 1/2, mTOR, p70S6, P13K, PTEN, SHC Y317, NFKB, IKB, CFK4, CDK2, cyclin D1, cyclin A, Cyclin E, p15, p16, p21, p27, beta-catenin, and ras gene mutation
|Study Start Date:||September 2011|
|Estimated Study Completion Date:||June 2016|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
Experimental: Bortezomib plus lapatinib
Combination treatment with lapatinib and bortezomib
Drug: Lapatinib and bortezomib
Lapatinib will be taken orally continuously for 28 days of each 28-day cycle, including a run-in of lapatinib alone day -7 to day 1 of cycle 1.
Bortezomib will be administered IV on days 1, 8, and 15 of each cycle. The exact doses of both drugs will be dependent on which cohort the subject is in and adverse events observed in previous cohorts.
Other Name: Velcade
Please refer to this study by its ClinicalTrials.gov identifier: NCT01497626
|United States, District of Columbia|
|Georgetown Lombardi Comprehensive Cancer Center|
|Washington, District of Columbia, United States, 20007|
|Principal Investigator:||Michael Pishvaian, MD PhD||Georgetown University|