Advanced LymphomaPhase 2NCT06303167
Testing AZD9291 as Potentially Targeted Treatment in Cancers With EGFR Genetic Changes (MATCH-Subprotocol E)
A Phase 2 study testing Biopsy Procedure, Biospecimen Collection and Echocardiography Test in people with Advanced Lymphoma and Advanced Malignant Solid Neoplasm, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This phase II MATCH treatment trial evaluates the effectiveness of osimertinib (AZD9291) in treating patients with cancer that has certain genetic changes called EGFR mutations. Osimertinib is in a class of medications called kinase inhibitors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Lymphoma, Advanced Malignant Solid Neoplasm, Hematopoietic and Lymphoid Cell Neoplasm
- What is being tested?
- Biopsy Procedure, Biospecimen Collection and Echocardiography Test
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Jan 2016to 15 Jan 2027
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have met applicable eligibility criteria in the Master MATCH Protocol EAY131/ NCI-2015-00054 prior to registration to treatment subprotocol
- Patient must fulfill all eligibility criteria outlined in MATCH Master Protocol at the time of registration to treatment step (step 1, 3, 5, 7)
- Patients must have either of the below, or another aberration, as determined via the MATCH Master Protocol:
- Any malignancy except non-small cell lung cancer (NSCLC) with EGFR T790M identified in their tumor, with or without an activating mutation OR
- Any malignancy harboring any of the following mutations: EGFR G719A, G719C, G719D, G719S EGFR L861Q, S786I or an EGFR exon 19 in frame insertion mutation
- 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, and second-degree heart block
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- Patients must have an ECHO or a nuclear study (MUGA or first pass) within 4 weeks prior to registration and must not have a left ventricular ejection fraction (LVEF) < institutional lower limit of normal (LLN). If the LLN is not defined at a site, the LVEF must be > 50% for the patient to be eligible
- Patients must not have known hypersensitivity to osimertinib (AZD9291) or compounds of similar chemical or biologic composition or any of the inactive excipients of the tablets
- Patient must not have received osimertinib (AZD9291), WZ4002, CO-1686, HM61713, EGF816 or ASP8273 previously
- Patients known to harbor germline EGFR T790M mutations are excluded from the study. Prospective testing for germline mutations is not required
- Patients must not have a history of interstitial lung disease, idiopathic pulmonary fibrosis, organizing pneumonia (eg, bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, radiation pneumonitis requiring steroids, or evidence of active pneumonitis on screening chest computerized tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted
- Patients must not currently be receiving treatment with potent CYP3A4 inducters or medications "known to prolong" the QT interval. Drugs that "may possibly prolong" the QT interval, are permitted if the patient has been stable on therapy for the period indicated for the specific medication
- Patients must agree to not donate sperm from the start of protocol treatment until at least 4 months after the last dose of protocol treatment
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
ECOG-ACRIN Cancer Research Group
Philadelphia, Pennsylvania, 19103
About this study
Official title: MATCH Treatment Subprotocol E: Osimertinib (AZD9291) in Patients With Tumors Having EGFR T790M Mutations or Rare Activating Mutations of EGFR
This phase II MATCH treatment trial evaluates the effectiveness of osimertinib (AZD9291) in treating patients with cancer that has certain genetic changes called EGFR mutations. Osimertinib is in a class of medications called kinase inhibitors. It works by blocking the action of mutant forms of the EGFR protein, which play a key role in tumor cell growth. Osimertinib may cause tumor cell death and inhibit tumor growth in EGFR-overexpressing tumor cells, thereby stopping or slowing the spread of tumor cells.
Read the detailed description
PRIMARY OBJECTIVE:
- 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:
- 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 osimertinib (AZD9291) 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. Patients also undergo radiologic evaluation throughout the trial, echocardiography (ECHO) or multigated acquisition scan (MUGA) during screening, and biopsy and collection of blood samples on trial and at end of treatment.
After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 1 year.
THE MATCH SCREENING TRIAL:
Please see NCT02465060 for information on the MATCH Screening Protocol and applicable documents.
- Conditions
- Advanced Lymphoma, Advanced Malignant Solid Neoplasm, Hematopoietic and Lymphoid Cell Neoplasm, Refractory Lymphoma, Refractory Malignant Solid Neoplasm, Refractory Multiple Myeloma
- Being tested
- Biopsy Procedure, Biospecimen Collection, Echocardiography Test, Multigated Acquisition Scan, Osimertinib
- Medical subject headings
- Hematologic Neoplasms, Lymphoma, Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biopsy ProcedureProcedure or surgery
Also called Biopsy, BIOPSY_TYPE, Bx
Undergo biopsy
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
Undergo blood sample collection
Echocardiography TestProcedure or surgery
Also called EC, Echocardiography
Undergo ECHO
Multigated Acquisition ScanProcedure or surgery
Also called Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan
Undergo MUGA
OsimertinibDrug
Also called AZD 9291, AZD-9291, AZD9291, Mereletinib
Given PO
Radiologic ExaminationProcedure or surgery
Also called Radiologic Evaluation, Radiologic Exam
Undergo radiologic evaluation
| Study group | Role | What they receive |
|---|---|---|
| Treatment (osimertinib) | Experimental | Patients receive osimertinib (AZD9291) PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo radiologic evaluation throughout the trial, ECHO or MUGA during screening, and biopsy and collection of blood samples on trial and at end of treatment. Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Echocardiography Test; Procedure: Multigated Acquisition Scan; Drug: Osimertinib; Procedure: Radiologic Examination |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate
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. Details about how to define complete response and partial response can be found in the master protocol. 90% two-sided binomial exact confidence interval is calculated for ORR.
Measured: Tumor assessments occurred at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration
Secondary outcomes (2)
6-month Progression-Free Survival (PFS) Rate
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.
Measured: Assessed at baseline, then every 2 cycles for the first 26 cycles, and every 3 cycles thereafter until disease progression, up to 3 years post registration, from which 6-month PFS rate is determined
Progression Free Survival
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.
Measured: Assessed at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2024
- Study start8 Jan 2016
- Primary completion26 Feb 2023
- Study completion15 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Advanced LymphomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Lecia V Sequist, Principal investigator, ECOG-ACRIN Cancer Research Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06303167
- Sponsor's protocol ID
- NCI-2024-01150
- Other IDs
- NCI-2024-01150, EAY131-E, EAY131-E, U10CA180820
- Status last verified
- Sep 2026
- First submitted
- 8 Mar 2024
- Last updated
- 15 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.