Back to results

Testing AZD1775 as a Potential Targeted Treatment in Cancers With BRCA Genetic Changes (MATCH-Subprotocol Z1I)

Primary Purpose

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

Status

Active

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Adavosertib

About this trial

This is an interventional treatment trial for Advanced Lymphoma

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 mutation in the BRCA1 or BRCA2 gene in the tumor, or another aberration, as determined via the MATCH Master Protocol. Patients with tumor carrying mutations defined as variants of uncertain significance will not qualify
Patients with ovarian cancer or HER2 negative, metastatic breast cancer must have received a PARP inhibitor as part of or as one of their prior lines of therapy
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 receiving any medications or substances that are inhibitors or inducers of CYP3A4, or CYP3A4 substrates need to be reviewed by the study investigator. Continuation of such medications will be at the discretion of the study investigator. Concomitant use of aprepitant and fosaprepitant is prohibited
Patients have hemoglobin (HgB) >= 9 g/dL, which should be done =< 4 weeks prior to registration to treatment step
Resting corrected QTc interval using the Fridericia formula (QTcF) should be < 450 msec/male and < 470 msec/female (as calculated per institutional standards) obtained from electrocardiogram (ECG), prior to enrollment. If resting QTc interval using the Fridericia formula (QTcF) is > 450 msec/male and > 470 msec/female (as calculated per institutional standards), then 2 additional ECGs should be performed 2-5 minutes apart at study entry. In order to be eligible, the mean resting corrected QTc interval using the Fridericia formula (QTcF) should be < 450 msec/male and < 470 msec/female (as calculated per institutional standards)

Exclusion Criteria:

Patients must not have known hypersensitivity to AZD1775 or compounds of similar chemical or biologic composition

Sites / Locations

ECOG-ACRIN Cancer Research Group

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (adavosertib)

Arm Description

Patients receive adavosertib PO QD on days 1-5 and 8-12 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Objective response rate (ORR)

ORR is defined as the percentage of patients whose tumors have a complete or partial response to treatment among eligible and treated patients. Objective response rate 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. For each treatment arm, 90% two-sided binomial exact confidence interval will be calculated for ORR.

Secondary Outcome Measures

Overall survival (OS)

OS is defined as time from treatment start date to date of death from any cause. Patients alive at the time of analysis are censored at last contact date. OS will be evaluated specifically for each drug (or step) using the Kaplan-Meier method.

Progression free survival (PFS)

Progression free survival is defined as time from treatment start date to date of progression or death from any cause, whichever occurs first. PFS will be estimated using the Kaplan-Meier method.

Full Information

NCT ID

NCT04439227

First Posted

June 18, 2020

Last Updated

July 6, 2023

Sponsor

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT04439227

Brief Title

Testing AZD1775 as a Potential Targeted Treatment in Cancers With BRCA Genetic Changes (MATCH-Subprotocol Z1I)

Official Title

MATCH Treatment Subprotocol Z1I: Phase II Study of AZD1775 in Patients With Tumors Containing BRCA1 and BRCA2 Mutations

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

March 13, 2017 (Actual)

Primary Completion Date

June 30, 2024 (Anticipated)

Study Completion Date

June 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This phase II MATCH treatment trial identifiesay block the protein tyrosine kinase WEE1 the effects of AZD1775 in patients whose cancer has a genetic change called BRCA mutation. AZD1775 may block a protein called WEE1, which may be needed for growth of cancer cells that express BRCA mutations. Researchers hope to learn if AZD1775 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 adavosertib (AZD1775) orally (PO) once daily (QD) on days 1-5 and 8-12 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months if less than 2 years from study entry, and then every 6 months for an additional year from study entry.

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 Multiple Myeloma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

35 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Treatment (adavosertib)

Arm Type

Experimental

Arm Description

Patients receive adavosertib PO QD on days 1-5 and 8-12 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Intervention Type

Drug

Intervention Name(s)

Adavosertib

Other Intervention Name(s)

AZD-1775, AZD1775, MK-1775, MK1775

Intervention Description

Given PO

Primary Outcome Measure Information:

Title

Objective response rate (ORR)

Description

Time Frame

Tumor assessments occurred at baseline, then every 3 cycles until disease progression, up to 3 years post registration

Secondary Outcome Measure Information:

Title

Overall survival (OS)

Description

Time Frame

Assessed every 3 months for =< 2 years and every 6 months for year 3

Title

Progression free survival (PFS)

Description

Progression free survival is defined as time from treatment start date to date of progression or death from any cause, whichever occurs first. PFS will be estimated using the Kaplan-Meier method.

Time Frame

Assessed at baseline, then every 3 cycles until disease progression, up to 3 years post registration

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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 mutation in the BRCA1 or BRCA2 gene in the tumor, or another aberration, as determined via the MATCH Master Protocol. Patients with tumor carrying mutations defined as variants of uncertain significance will not qualify Patients with ovarian cancer or HER2 negative, metastatic breast cancer must have received a PARP inhibitor as part of or as one of their prior lines of therapy 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 receiving any medications or substances that are inhibitors or inducers of CYP3A4, or CYP3A4 substrates need to be reviewed by the study investigator. Continuation of such medications will be at the discretion of the study investigator. Concomitant use of aprepitant and fosaprepitant is prohibited Patients have hemoglobin (HgB) >= 9 g/dL, which should be done =< 4 weeks prior to registration to treatment step Resting corrected QTc interval using the Fridericia formula (QTcF) should be < 450 msec/male and < 470 msec/female (as calculated per institutional standards) obtained from electrocardiogram (ECG), prior to enrollment. If resting QTc interval using the Fridericia formula (QTcF) is > 450 msec/male and > 470 msec/female (as calculated per institutional standards), then 2 additional ECGs should be performed 2-5 minutes apart at study entry. In order to be eligible, the mean resting corrected QTc interval using the Fridericia formula (QTcF) should be < 450 msec/male and < 470 msec/female (as calculated per institutional standards) Exclusion Criteria: Patients must not have known hypersensitivity to AZD1775 or compounds of similar chemical or biologic composition

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Shivaani Kummar

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

Learn more about this trial

Testing AZD1775 as a Potential Targeted Treatment in Cancers With BRCA Genetic Changes (MATCH-Subprotocol Z1I)

We'll reach out to this number within 24 hrs