MLN0128 and Bevacizumab in Treating Patients With Recurrent Glioblastoma or Advanced Solid Tumors
This phase I trial studies the side effects and best dose of MLN0128 when given in combination with bevacizumab in treating patients with glioblastoma, a type of brain tumor, or a solid tumor that has spread and not responded to standard treatment. MLN0128 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Bevacizumab may also stop the progression of tumors by blocking the growth of new blood vessels necessary for tumor growth.
Adult Giant Cell Glioblastoma
Adult Solid Neoplasm
Endometrial Clear Cell Adenocarcinoma
Endometrial Serous Adenocarcinoma
Ovarian Clear Cell Cystadenocarcinoma
Ovarian Endometrioid Adenocarcinoma
Ovarian Mucinous Cystadenocarcinoma
Ovarian Serous Cystadenocarcinoma
Recurrent Adult Brain Neoplasm
Recurrent Fallopian Tube Carcinoma
Recurrent Ovarian Carcinoma
Recurrent Primary Peritoneal Carcinoma
Recurrent Uterine Corpus Carcinoma
Stage IIIA Fallopian Tube Cancer
Stage IIIA Ovarian Cancer
Stage IIIA Primary Peritoneal Cancer
Stage IIIB Fallopian Tube Cancer
Stage IIIB Ovarian Cancer
Stage IIIB Primary Peritoneal Cancer
Stage IIIC Fallopian Tube Cancer
Stage IIIC Ovarian Cancer
Stage IIIC Primary Peritoneal Cancer
Stage IV Fallopian Tube Cancer
Stage IV Ovarian Cancer
Stage IV Primary Peritoneal Cancer
Drug: TORC1/2 Inhibitor INK128
Other: Pharmacological Study
Other: Laboratory Biomarker Analysis
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 1 Study of MLN0128 and Bevacizumab in Patients With Recurrent Glioblastoma and Other Solid Tumors|
- MTD/RP2D of MLN0128, determined according to incidence of dose-limiting toxicity, as graded using the National Cancer Institute (NCI) CTCAE version 4.0 [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
- Incidence of adverse events, graded according to NCI CTCAE version 4.0 [ Time Frame: Up to 30 days ] [ Designated as safety issue: No ]Safety will be assessed through summaries of adverse events, changes in selected laboratory test results, changes in vital signs, and MLN0128 and bevacizumab exposure.
- PFS [ Time Frame: From date of first dose to date of progression or death, assessed at 6 months ] [ Designated as safety issue: No ]Listed for all patients by dose level.
- Objective RR, defined as a complete or partial response, as determined by investigator assessment using RECIST or RANO [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
- OS [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]Listed for all patients by dose level.
- Frequency of toxicities leading to missed doses or delays [ Time Frame: Up to 30 days ] [ Designated as safety issue: Yes ]Percentage will be summarized.
- Percentage of courses given or not within 7 days of their scheduled times [ Time Frame: Up to 30 days ] [ Designated as safety issue: Yes ]Percentage will be summarized.
- Percentage of actual planned dosage administration [ Time Frame: Up to 30 days ] [ Designated as safety issue: Yes ]Percentage will be summarized.
- Percentage of patients that discontinue study drugs due to treatment related toxicity [ Time Frame: Up to 30 days ] [ Designated as safety issue: Yes ]Percentage will be summarized.
- CSF penetration of MLN0128, evaluated using plasma and CSF pharmacokinetic (PK) parameters of MLN0128 [ Time Frame: 2-3 hours post-dose day 15 of course 1 and day 1 of course 2 ] [ Designated as safety issue: No ]Plasma and CSF PK levels of MLN0128 obtained before and after bevacizumab administration will be evaluated and summarized. The ration of plasma to CSF PK levels will also be summarized.
- Markers associated with dysregulated cell signaling [ Time Frame: Baseline ] [ Designated as safety issue: No ]The biomarkers predicting response to mTOR inhibitor activity will be resulted by dose level and response status.
- Change in phosphorylated proteins within tumor biopsies from patients with ovarian and endometrial cancers [ Time Frame: Baseline to within 7 days after last study drug or within 7 days after decision to end treatment ] [ Designated as safety issue: No ]
- Change in circulating plasma levels of angiogenic growth factors in patients with ovarian and endometrial cancers [ Time Frame: Baseline to day 1 of last course of treatment ] [ Designated as safety issue: No ]
- Mutation analysis of tissue from biopsies of patients with ovarian and endometrial cancers [ Time Frame: Baseline ] [ Designated as safety issue: No ]
|Study Start Date:||May 2014|
|Estimated Primary Completion Date:||November 2014 (Final data collection date for primary outcome measure)|
Experimental: Treatment (MLN0128, bevacizumab)
Patients receive MLN0128 PO QD on days 1-28 and bevacizumab IV on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: TORC1/2 Inhibitor INK128
Other Names:Biological: Bevacizumab
Other Names:Other: Pharmacological Study
Other Name: pharmacological studiesOther: Laboratory Biomarker Analysis
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT02142803
|United States, Massachusetts|
|Dana-Farber Cancer Institute||Recruiting|
|Boston, Massachusetts, United States, 02115|
|Contact: Lakshmi Nayak 617-632-2166 Lakshmi_Nayak@DFCI.harvard.edu|
|Principal Investigator: Lakshmi Nayak|
|Massachusetts General Hospital Cancer Center||Recruiting|
|Boston, Massachusetts, United States, 02114|
|Contact: Andrew S. Chi 617-724-8770 firstname.lastname@example.org|
|Principal Investigator: Andrew S. Chi|
|United States, Michigan|
|Barbara Ann Karmanos Cancer Institute||Recruiting|
|Detroit, Michigan, United States, 48201|
|Contact: Patricia M. LoRusso 313-576-8716 email@example.com|
|Principal Investigator: Patricia M. LoRusso|
|United States, Ohio|
|Ohio State University Medical Center||Not yet recruiting|
|Columbus, Ohio, United States, 43210|
|Contact: John L. Hays 614-685-5840 firstname.lastname@example.org|
|Principal Investigator: John L. Hays|
|Principal Investigator:||Lakshmi Nayak||Dana-Farber Cancer Institute|