- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06385496
Testing MLN0128 (TAK-228) as Potentially Targeted Treatment in Cancers With mTOR Genetic Changes (MATCH - Subprotocol L)
MATCH Treatment Subprotocol L: Phase II Study of MLN0128 (TAK-228) in Patients With Tumors Wtih mTOR Mutations
Study Overview
Status
Conditions
Detailed Description
PRIMARY OBJECTIVE:
I. To evaluate the proportion of patients with objective response (OR) to targeted study agent(s) in patients with advanced refractory cancers/lymphomas/multiple myeloma.
SECONDARY OBJECTIVES:
I. To evaluate the proportion of patients alive and progression free at 6 months of treatment with targeted study agent in patients with advanced refractory cancers/lymphomas/multiple myeloma.
II. To evaluate time until death or disease progression. III. To identify potential predictive biomarkers beyond the genomic alteration by which treatment is assigned or resistance mechanisms using additional genomic, ribonucleic acid (RNA), protein and imaging-based assessment platforms.
IV. To assess whether radiomic phenotypes obtained from pre-treatment imaging and changes from pre- through post-therapy imaging can predict objective response and progression free survival and to evaluate the association between pre-treatment radiomic phenotypes and targeted gene mutation patterns of tumor biopsy specimens.
OUTLINE:
Patients receive sapanisertib (MLN0128 [TAK-228]) orally (PO) once daily (QD) on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo computed tomography (CT) or magnetic resonance imaging (MRI) during screening and on study, as well as during follow-up as clinically necessary. Patients also undergo biopsies and blood sample collection on study.
After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 1 year.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Pennsylvania
-
Philadelphia, Pennsylvania, United States, 19103
- ECOG-ACRIN Cancer Research Group
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Patients must have met applicable eligibility criteria in the Master MATCH Protocol EAY131/ NCI-2015-00054 prior to registration to treatment subprotocol
- Patients must fulfill all eligibility criteria of MATCH Master Protocol at the time of registration to treatment step (Step 1, 3, 5, 7)
- Patients must have a mutation in mTOR, KEAP1 or NFE2L2 as determined via the MATCH Master Protocol
Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must NOT have any of the following cardiac criteria:
- Clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block, Corrected QT Interval [QTc] interval > 480 milliseconds)
- Uncontrolled hypertension (i.e., systolic blood pressure >180 mm Hg, diastolic blood pressure > 95 mm Hg). Use of anti-hypertensive agents to control hypertension before cycle 1, day 1 is allowed
- Known pulmonary hypertension.
- Patients must not have known hypersensitivity to MLN0128 or compounds of similar chemical or biologic composition
- Patients must not have known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection, but may have had previously treated and successfully eradicated hepatitis C virus (HCV)
- Patients must have none of the following within six months of receiving the first dose of MLN0128 (TAK-228): ischemic, myocardial or cerebrovascular event, class III or IV heart failure, placement of pacemaker, or pulmonary embolism
- Patients must have no manifestations of malabsorption due to prior gastrointestinal (GI) surgery, GI disease, or for an unknown reason that may alter the absorption of MLN0128 (TAK-228)
Patients who have a history of brain metastasis are eligible for the study provided that all the following criteria are met:
- Brain metastases which have been treated
- No evidence of disease progression for >= 1 months before the first dose of study drug
- No hemorrhage after treatment
- Off-treatment with dexamethasone for 4 weeks before administration of the first dose of MLN0128 (TAK-228)
- No ongoing requirement for dexamethasone or anti-epileptic drugs
Patients meeting the following criteria for concomitant medications prior to starting MLN0128 (TAK-228) are not eligible for the study:
- Patients who use a proton pump inhibitor (PPI) within 7 days before receiving the first dose of study drug.
- Patients who would require treatment with PPIs throughout the trial
- Patients who would need to take H2 receptor antagonists within 24 hours of the first dose of study drug NOTE Strong CYP1A2 inhibitors and CYP inducers should be administered with caution, at the discretion of the investigator. Alternative treatments, if available, should be considered
- Patients must not have known treatment with systemic corticosteroid within one week prior to the first administration of study drug
- Patients must not have uncontrolled diabetes mellitus. Controlled diabetes is defined as: Glycosylated hemoglobin (HbA1c) < 7.0%, or fasting serum glucose (=< 130 mg/dL)
- Patients must not have fasting triglycerides >= 300 mg/dL
Patients must not have had prior treatment with other known TORC1/2 inhibitors, including:
- AZD8055
- XL765
- BEZ235
- GSK2126458
- XL388
- DS3078(a)
- PF-05212384
- SF1126
- Palomid-529
- GDC0980 (apitolisib)
- LY30223414
- BKM120
- OSI0127
- MLN0128 (TAK-228)
- AZD2014
- Patients must not have other clinically significant co-morbidities that, in the opinion of the investigator, would limit compliance with study requirements
- Fertility and developmental studies with MLN0128 (TAK-228) have not been conducted. On the basis of potential hazard of other mTOR inhibitors (i.e., rapamycin and other rapalogs) on the developing fetus, women of childbearing age should avoid becoming pregnant while taking MLN0128 (TAK-228). For this reason, women of child-bearing potential and men must agree to practice 1 highly effective method of contraception and 1 additional effective (barrier) method of contraception, at the same time, from the time of signing the informed consent through 120 days after the last dose of study drug, or agree to completely abstain from heterosexual intercourse. Men must agree not to donate sperm during the course of this study or within 120 days after receiving their last dose of study drug
- Patients who are known to be HIV-positive are not eligible for this study
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (sapanisertib [MLN0128 (TAK-228)])
Patients receive sapanisertib (MLN0128 [TAK-228]) PO QD on days 1-28 of each cycle.
Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Additionally, patients undergo CT or MRI during screening and on study, as well as during follow-up as clinically necessary.
Patients also undergo biopsies and blood sample collection on study.
|
Undergo MRI
Other Names:
Undergo blood sample collection
Other Names:
Given PO
Other Names:
Undergo biopsy
Other Names:
Undergo CT scan
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective response rate (ORR)
Time Frame: Up to 3 years
|
ORR is defined as the percentage of patients whose tumors have a complete or partial response to treatment among analyzable patients. Objective response is defined consistent with Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. 90% two-sided confidence interval is calculated for ORR. For the purposes of this study, patients should be re-evaluated for response:
|
Up to 3 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression free survival
Time Frame: From start of treatment on that step until determination of disease progression or death from any cause, censored at the date of last disease assessment for patients who have not progressed, assessed up to 3 years
|
PFS was defined as time from treatment start date to date of disease progression or death from any causes, whichever occurred first.
Median PFS was estimated using the Kaplan-Meier method.
Disease progression was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients.
Please refer to the protocol for detailed definitions of disease progression.
|
From start of treatment on that step until determination of disease progression or death from any cause, censored at the date of last disease assessment for patients who have not progressed, assessed up to 3 years
|
Overall survival (OS)
Time Frame: From start of treatment on that step until death, or censored at the date of last contact, assessed up to 3 years
|
Will be evaluated specifically for each drug (or step).
OS will be estimated using the Kaplan-Meier method.
|
From start of treatment on that step until death, or censored at the date of last contact, assessed up to 3 years
|
6-month progression free survival (PFS)
Time Frame: From start of treatment on that step until determination of disease progression or death from any cause, censored at the date of last disease assessment for patients who have not progressed, assessed at 6 months
|
Progression free survival is defined as time from treatment start date to date of progression or death from any cause, whichever occurs first.
Disease progression was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients.
Please refer to the protocol for detailed definitions of disease progression.
6 month PFS rate was estimated using the Kaplan-Meier method, which can provide a point estimate for any specific time point.
|
From start of treatment on that step until determination of disease progression or death from any cause, censored at the date of last disease assessment for patients who have not progressed, assessed at 6 months
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: John L Hays, ECOG-ACRIN Cancer Research Group
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Neoplasms, Plasma Cell
- Neoplasms
- Lymphoma
- Multiple Myeloma
Other Study ID Numbers
- NCI-2024-01145 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- U10CA180820 (U.S. NIH Grant/Contract)
- EAY131-L (Other Identifier: CTEP)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Advanced Lymphoma
-
Bristol-Myers SquibbTerminatedAdvanced Solid Tumors | Advanced B-cell NHLUnited States, France, Spain, Germany
-
National Cancer Institute (NCI)Active, not recruitingAdvanced Lymphoma | Advanced Malignant Solid Neoplasm | Refractory Lymphoma | Refractory Malignant Solid NeoplasmUnited States
-
Adlai Nortye Biopharma Co., Ltd.RecruitingAdvanced Solid Tumor | Advanced LymphomaUnited States, China
-
CStone PharmaceuticalsRecruitingAdvanced Solid Tumor | Advanced LymphomaChina, Australia, United States
-
Lee's Pharmaceutical LimitedUnknownAdvanced Hodgkin's Lymphoma
-
National Cancer Institute (NCI)Active, not recruitingHematopoietic and Lymphoid Cell Neoplasm | Advanced Lymphoma | Advanced Malignant Solid Neoplasm | Refractory Lymphoma | Refractory Malignant Solid NeoplasmUnited States
-
Hoffmann-La RocheCompletedAdvanced Follicular LymphomaGermany, Brazil, United Kingdom, Spain, Japan, United States, Netherlands
-
National Cancer Institute (NCI)Not yet recruitingAdvanced Lymphoma | Advanced Malignant Solid Neoplasm | Metastatic Malignant Solid Neoplasm
-
BayerCompletedNon-Hodgkin's Lymphoma | Mantle Cell Lymphoma | Advanced Solid TumorUnited States, Canada, China, Japan, Singapore, United Kingdom, Switzerland
-
Curon Biopharmaceutical (Australia) Co Pty LtdNovotech (Australia) Pty LimitedCompletedB Cell Lymphoma | Advanced Solid TumorAustria
Clinical Trials on Magnetic Resonance Imaging
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)CompletedHematopoietic and Lymphoid Cell Neoplasm | Malignant Solid NeoplasmUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Recruiting
-
M.D. Anderson Cancer CenterActive, not recruitingProstate Adenocarcinoma | Prostate CarcinomaUnited States
-
OHSU Knight Cancer InstituteOregon Health and Science UniversityRecruitingIntracranial NeoplasmUnited States
-
University of California, San FranciscoTerminatedAnatomic Stage I Breast Cancer AJCC v8 | Anatomic Stage IA Breast Cancer AJCC v8 | Anatomic Stage IB Breast Cancer AJCC v8 | Anatomic Stage II Breast Cancer AJCC v8 | Anatomic Stage IIA Breast Cancer AJCC v8 | Anatomic Stage IIB Breast Cancer AJCC v8 | Anatomic Stage III Breast Cancer AJCC v8 | Anatomic... and other conditionsUnited States
-
Wake Forest University Health SciencesNational Cancer Institute (NCI)CompletedStage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIA Breast Cancer | Stage IIB Breast Cancer | Stage IIIC Breast Cancer | Healthy SubjectUnited States
-
Stanford UniversityTerminatedLaryngeal Neoplasms | Head and Neck Cancers | Larynx CancerUnited States
-
Vanderbilt-Ingram Cancer CenterNational Cancer Institute (NCI)CompletedBreast CancerUnited States
-
Abramson Cancer Center of the University of PennsylvaniaCompletedBrain TumorUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)TerminatedThoracic Spine NeoplasmUnited States