Study of TAK-228 (MLN0128) in Soft Tissue Sarcomas
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|ClinicalTrials.gov Identifier: NCT02987959|
Recruitment Status : Active, not recruiting
First Posted : December 9, 2016
Results First Posted : February 24, 2021
Last Update Posted : February 24, 2021
This is an open-label phase II study of TAK-228 for patients ≥ 18 years of age with complex genomic sarcomas exhibiting Phosphoinositide-3 Kinase (PI3K) pathway dysregulation. Patients must have surgically unresectable or metastatic disease that is refractory to at least one prior line of therapy (not including neoadjuvant or adjuvant therapy in a curative setting). Patients disease must also have evidence of progression prior to enrollment. The purpose of this study is to determine the antitumor activity in this group of patients. Patients must meet all eligibility criteria as detailed in section 10. A total of up to 33 patients will be included in the study. Patients will undergo screening evaluations to determine eligibility within 28 days of the first dose. All patients will be required to submit baseline tumor samples for analysis. Patients who have had their tumors tested commercially for PI3K/ AKT/mechanistic Target of Rapamycin (mTOR) alterations will be assessed on a case by case basis for eligibility and for determination as to whether additional tissue is required.
TAK-228 will be administered orally at 3 mg daily for a 21 day cycle. Clinical and laboratory assessments will be made on day 1 of each cycle. Disease will be assessed by comparing unidimensional tumor measurements on pre and peritreatment imaging (CT or MRI) after weeks 6, 12, 18 and every 12 weeks thereafter. Response will be assessed according to RECIST 1.1. Therapy will continue until disease progression or unacceptable toxicity or withdrawal of consent.
|Condition or disease||Intervention/treatment||Phase|
|Soft-tissue Sarcoma||Drug: TAK-228||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||6 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Study of TAK-228 (MLN0128) in Soft Tissue Sarcomas With Dysregulation of the mTOR Pathway|
|Actual Study Start Date :||February 21, 2017|
|Actual Primary Completion Date :||January 30, 2019|
|Estimated Study Completion Date :||September 2021|
Experimental: TAK-228 treatment
Patients with complex genomic sarcomas exhibiting PI3K pathway dysregulation will be treated with TAK-228
TAK-228 is a novel, highly selective, orally bioavailable adenosine 5' triphosphate (ATP)-competitive inhibitor of the serine/threonine kinase referred to as the mechanistic target of rapamycin (mTOR). TAK-228 (formerly INK128) targets 2 distinct mTOR complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2).
Other Name: MLN0128
- The Progression Free Survival Rate With TAK-228 in Sarcoma Patients With PI3K/AKT/mTOR Pathway Dysregulation [ Time Frame: 12 weeks post-treatment ]Progression free rate will be determined by determining the number of patients with complete response, partial response and stable disease
- The Rate of Toxicity of TAK-228 in This Patient Population as Per Common Terminology Criteria for Adverse Events (CTCAE)v4.03 Criteria. [ Time Frame: 1 year ]Toxicity will be assessed by calculating number of participants experiencing adverse events as per CTCAEv4.03 criteria
- The Objective Response Rate (ORR) of TAK-228 in This Patient Population. [ Time Frame: upto 4 years ]Objective response rate will be defined as patients with complete response and partial response. As per RECIST v1.1 guidelines, complete response is defined as the disappearance of all measurable lesions, and partial response is defined as >=30% decrease in sum of diameters of target lesions compared to the baseline sum of diameters.
- Progression Free Survival in This Patient Population. [ Time Frame: upto 4 years ]Progression Free Survival, defined as the time from initiation of treatment until disease progression will be calculated.
- Overall Survival Rate in This Patient Population [ Time Frame: upto 4 years ]Overall Survival, defined as the time from initiation of treatment until death from any cause will be calculated.
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): NCT02987959
|United States, Pennsylvania|
|Fox Chase Cancer Center|
|Philadelphia, Pennsylvania, United States, 19111|