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Testing AZD4547 as a Potential Targeted Treatment in Cancers With FGFR Genetic Changes (MATCH-Subprotocol W)

Primary Purpose

Advanced Lymphoma, Advanced Malignant Solid Neoplasm, Hematopoietic and Lymphoid Cell Neoplasm

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
FGFR Inhibitor AZD4547
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Lymphoma focused on measuring FGFR, AZD4547, NCI-MATCH

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol
  • Patients must have FGFR 1-3 mutation or translocation 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 have an echocardiogram (ECHO) or a nuclear study (multigated acquisition scan [MUGA] or First Pass) within 4 weeks prior to registration to treatment 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 have a pre-study eye exam by an ophthalmologist. Patients with current evidence of corneal or retinal disorder/keratopathy are excluded

Exclusion Criteria:

  • Patients must not have known hypersensitivity to AZD4547 or compounds of similar chemical or biologic composition
  • Patients must not have received prior FGFR specific inhibitors (e.g. BGJ398, erdafitinib, BAY1163877, LY2874455). Prior non-selective FGFR inhibitor treatment (e.g. pazopanib, dovitinib, ponatinib, brivanib, lucitanib, lenvatinib) will be allowed
  • Patients must not have any history of or current evidence of renal or endocrine alterations of calcium/phosphate homeostasis, or history of or current evidence of extensive tissue calcification (by evaluation of the clinician), including but not limited to, the soft tissue, kidneys, intestine, myocardium and lung with the exception of calcified lymph nodes and asymptomatic vascular calcification per investigators' judgment

  • Patients must not be currently using medications that can elevate serum phosphorous and/or calcium levels

    • Medications that increase serum calcium should be avoided. Over the counter calcium supplements, antacids that contain calcium (Tums) and vitamin D supplements (cholecalciferol and ergocalciferol) should be avoided. Prescription medications including lithium, hydrochlorothiazide and chlorthalidone must be used with caution
    • Medications that increase serum phosphate should be avoided. Over the counter laxatives that contain phosphate such as Fleets Oral or Fleets enema and Miralax should be avoided

Sites / Locations

  • ECOG-ACRIN Cancer Research Group

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (AZD4547)

Arm Description

Patients receive AZD4547 PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Overall Response Rate (ORR)
Overall response rate was defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR) among all eligible and treated patients. Best overall response 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. The 90% two-sided binomial exact confidence interval was calculated for ORR.

Secondary Outcome Measures

6-month Progression-free Survival (PFS) Rate
PFS was defined as time from treatment start date to date of disease progression or death from any causes, whichever occurred first. The 6-month PFS rate was estimated using the Kaplan-Meier method which can provide a point estimate for any specific time point. 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.
Progression Free Survival (PFS)
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.

Full Information

First Posted
June 18, 2020
Last Updated
June 8, 2021
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT04439240
Brief Title
Testing AZD4547 as a Potential Targeted Treatment in Cancers With FGFR Genetic Changes (MATCH-Subprotocol W)
Official Title
MATCH Treatment Subprotocol W: Phase II Study of AZD4547 in Patients With Tumors With Aberrations in the FGFR Pathway
Study Type
Interventional

2. Study Status

Record Verification Date
June 2021
Overall Recruitment Status
Completed
Study Start Date
May 31, 2016 (Actual)
Primary Completion Date
June 6, 2019 (Actual)
Study Completion Date
June 30, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This phase II MATCH treatment trial identifies the effects of AZD4547 in patients whose cancer has genetic changes called FGFR gene alterations. AZD4547 may stop the growth of cancer cells by blocking FGFR proteins which may be needed for cell growth. Researchers hope to learn if AZD4547 will shrink this type of cancer or stop its growth.
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 FGFR inhibitor AZD4547 (AZD4547) orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months if less than 2 years from study entry, and then every 6 months for year 3 from study entry. THE MATCH SCREENING TRIAL: Please see NCT02465060 for information on the MATCH Screening Protocol and applicable documents.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Lymphoma, Advanced Malignant Solid Neoplasm, Hematopoietic and Lymphoid Cell Neoplasm, Refractory Lymphoma, Refractory Malignant Solid Neoplasm, Refractory Plasma Cell Myeloma
Keywords
FGFR, AZD4547, NCI-MATCH

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
52 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (AZD4547)
Arm Type
Experimental
Arm Description
Patients receive AZD4547 PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
FGFR Inhibitor AZD4547
Other Intervention Name(s)
AZD4547
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
Overall response rate was defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR) among all eligible and treated patients. Best overall response 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. The 90% two-sided binomial exact confidence interval was calculated for ORR.
Time Frame
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
Secondary Outcome Measure Information:
Title
6-month Progression-free Survival (PFS) Rate
Description
PFS was defined as time from treatment start date to date of disease progression or death from any causes, whichever occurred first. The 6-month PFS rate was estimated using the Kaplan-Meier method which can provide a point estimate for any specific time point. 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.
Time Frame
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 is determined
Title
Progression Free Survival (PFS)
Description
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.
Time Frame
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol Patients must have FGFR 1-3 mutation or translocation 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 have an echocardiogram (ECHO) or a nuclear study (multigated acquisition scan [MUGA] or First Pass) within 4 weeks prior to registration to treatment 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 have a pre-study eye exam by an ophthalmologist. Patients with current evidence of corneal or retinal disorder/keratopathy are excluded Exclusion Criteria: Patients must not have known hypersensitivity to AZD4547 or compounds of similar chemical or biologic composition Patients must not have received prior FGFR specific inhibitors (e.g. BGJ398, erdafitinib, BAY1163877, LY2874455). Prior non-selective FGFR inhibitor treatment (e.g. pazopanib, dovitinib, ponatinib, brivanib, lucitanib, lenvatinib) will be allowed Patients must not have any history of or current evidence of renal or endocrine alterations of calcium/phosphate homeostasis, or history of or current evidence of extensive tissue calcification (by evaluation of the clinician), including but not limited to, the soft tissue, kidneys, intestine, myocardium and lung with the exception of calcified lymph nodes and asymptomatic vascular calcification per investigators' judgment Patients must not be currently using medications that can elevate serum phosphorous and/or calcium levels Medications that increase serum calcium should be avoided. Over the counter calcium supplements, antacids that contain calcium (Tums) and vitamin D supplements (cholecalciferol and ergocalciferol) should be avoided. Prescription medications including lithium, hydrochlorothiazide and chlorthalidone must be used with caution Medications that increase serum phosphate should be avoided. Over the counter laxatives that contain phosphate such as Fleets Oral or Fleets enema and Miralax should be avoided
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Young Kwang Chae
Organizational Affiliation
ECOG-ACRIN Cancer Research Group
Official's Role
Principal Investigator
Facility Information:
Facility Name
ECOG-ACRIN Cancer Research Group
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19103
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
32463741
Citation
Chae YK, Hong F, Vaklavas C, Cheng HH, Hammerman P, Mitchell EP, Zwiebel JA, Ivy SP, Gray RJ, Li S, McShane LM, Rubinstein LV, Patton D, Williams PM, Hamilton SR, Mansfield A, Conley BA, Arteaga CL, Harris LN, O'Dwyer PJ, Chen AP, Flaherty KT. Phase II Study of AZD4547 in Patients With Tumors Harboring Aberrations in the FGFR Pathway: Results From the NCI-MATCH Trial (EAY131) Subprotocol W. J Clin Oncol. 2020 Jul 20;38(21):2407-2417. doi: 10.1200/JCO.19.02630. Epub 2020 May 28.
Results Reference
result
Links:
URL
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367548/
Description
Related Info

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Testing AZD4547 as a Potential Targeted Treatment in Cancers With FGFR Genetic Changes (MATCH-Subprotocol W)

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