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

NCT04439227 | Active Not Recruiting Phase 2 DMC FDA Drug

• 4 other identifiers: NCI-2020-03212EAY131-Z1IU10CA180820U24CA196172
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

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.

Conditions

Advanced Lymphoma; Advanced Malignant Solid Neoplasm; Hematopoietic and Lymphoid Cell Neoplasm; Refractory Lymphoma; Refractory Malignant Solid Neoplasm; Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• 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.

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

Secondary Outcomes (2)

• Overall survival (OS)

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

• Progression free survival (PFS)

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

Study Arms (1)

Treatment (adavosertib)

EXPERIMENTAL

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.

Drug: Adavosertib

Interventions

Adavosertib DRUG

Given PO

Also known as: AZD 1775, AZD-1775, AZD1775, MK 1775, MK-1775, MK1775

Treatment (adavosertib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

ECOG-ACRIN Cancer Research Group

Philadelphia, Pennsylvania, 19103, United States

Location

MeSH Terms

Conditions

Hematologic Neoplasms; Lymphoma; Multiple Myeloma

Interventions

adavosertib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders

Study Officials

• Shivaani Kummar

  ECOG-ACRIN Cancer Research Group

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2020
• First Posted: June 19, 2020
• Study Start: March 13, 2017
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 4, 2026

Record last verified: 2026-04

Locations

US (1)