TORC1/2 Inhibitor MLN0128 and Bevacizumab in Treating Patients With Recurrent Glioblastoma or Advanced Solid Tumors
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|ClinicalTrials.gov Identifier: NCT02142803|
Recruitment Status : Active, not recruiting
First Posted : May 20, 2014
Last Update Posted : October 15, 2019
|Condition or disease||Intervention/treatment||Phase|
|Adult Glioblastoma Endometrial Clear Cell Adenocarcinoma Endometrial Serous Adenocarcinoma Ovarian Clear Cell Cystadenocarcinoma Ovarian Endometrioid Adenocarcinoma Ovarian Mucinous Cystadenocarcinoma Ovarian Serous Cystadenocarcinoma Recurrent Fallopian Tube Carcinoma Recurrent Ovarian Carcinoma Recurrent Primary Peritoneal Carcinoma Recurrent Uterine Corpus Carcinoma Solid Neoplasm Stage IIIA Fallopian Tube Cancer AJCC v7 Stage IIIA Ovarian Cancer AJCC v6 and v7 Stage IIIA Primary Peritoneal Cancer AJCC v7 Stage IIIB Fallopian Tube Cancer AJCC v7 Stage IIIB Ovarian Cancer AJCC v6 and v7 Stage IIIB Primary Peritoneal Cancer AJCC v7 Stage IIIC Fallopian Tube Cancer AJCC v7 Stage IIIC Ovarian Cancer AJCC v6 and v7 Stage IIIC Primary Peritoneal Cancer AJCC v7 Stage IV Fallopian Tube Cancer AJCC v6 and v7 Stage IV Ovarian Cancer AJCC v6 and v7 Stage IV Primary Peritoneal Cancer AJCC v7||Biological: Bevacizumab Other: Laboratory Biomarker Analysis Other: Pharmacological Study Drug: Sapanisertib||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||58 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1 Study of MLN0128 and Bevacizumab in Patients With Recurrent Glioblastoma and Other Solid Tumors|
|Actual Study Start Date :||May 20, 2014|
|Estimated Primary Completion Date :||December 31, 2019|
Experimental: Treatment (TORC1/2 inhibitor INK128, bevacizumab)
Patients receive TORC1/2 inhibitor INK128 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.
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
- MTD/RP2D of TORC1/2 inhibitor 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 ]
- Incidence of adverse events, graded according to NCI CTCAE version 4.0 [ Time Frame: Up to 30 days ]Safety will be assessed through summaries of adverse events, changes in selected laboratory test results, changes in vital signs, and TORC1/2 inhibitor MLN0128 and bevacizumab exposure.
- PFS [ Time Frame: From date of first dose to date of progression or death, assessed at 6 months ]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 ]
- OS [ Time Frame: Up to 1 year ]Listed for all patients by dose level.
- Frequency of toxicities leading to missed doses or delays [ Time Frame: Up to 30 days ]Percentage will be summarized.
- Percentage of courses given or not within 7 days of their scheduled times [ Time Frame: Up to 30 days ]Percentage will be summarized.
- Percentage of actual planned dosage administration [ Time Frame: Up to 30 days ]Percentage will be summarized.
- Percentage of patients that discontinue study drugs due to treatment related toxicity [ Time Frame: Up to 30 days ]Percentage will be summarized.
- CSF penetration of TORC1/2 inhibitor 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 ]Plasma and CSF PK levels of TORC1/2 inhibitor 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 ]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 ]
- 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 ]
- Mutation analysis of tissue from biopsies of patients with ovarian and endometrial cancers [ Time Frame: Baseline ]
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): NCT02142803
|United States, Massachusetts|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02215|
|Massachusetts General Hospital|
|Charlestown, Massachusetts, United States, 02129|
|United States, Ohio|
|Ohio State University Comprehensive Cancer Center|
|Columbus, Ohio, United States, 43210|
|Principal Investigator:||Lakshmi Nayak||Dana-Farber Cancer Institute|