- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06390852
Testing LOXO-101 as Potentially Targeted Treatment in Cancers With NTRK Genetic Changes (MATCH - Subprotocol Z1E)
MATCH Treatment Subprotocol Z1E: Larotrectinib (LOXO-101) in Patients With Tumors With NTRK Fusions
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 larotrectinib (LOXO-101) orally (PO) twice daily (BID) 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 malignancy harboring an NTRK1, NTRK2 or NTRK3 gene fusion, as determined by the MATCH screening assessment
- Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have no clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block)
- Patients must not have known hypersensitivity to larotrectinib (LOXO-101) or compounds of similar chemical or biologic composition
- Patients with inability to discontinue treatment with a strong CYP3A4 inhibitor or inducer prior to start of treatment are excluded
- Patients who have previously received treatment with a TRKA, TRKB, or TRKC inhibitor are excluded. Such inhibitors include larotrectinib (LOXO-101), entrectinib (RXDX-101), TSR-011, DS6051, altiratinib (DCC-2701), MGCD516, dovitinib (TKI258, CHIR528), AZD7451, PLX7486, and BIBF1120
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 (larotrectinib [LOXO-101])
Patients receive larotrectinib (LOXO-101) PO BID 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: David S Hong, 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-2024-01138 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- U10CA180820 (U.S. NIH Grant/Contract)
- EAY131-Z1E (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
product manufactured in and exported from the U.S.
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.
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