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Testing AZD5363 as a Potential Targeted Treatment in Cancers With AKT Genetic Changes (MATCH-Subprotocol Y)

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

Capivasertib

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 an AKT mutation as determined via the MATCH Master Protocol
Patients with hormone receptor positive, defined as estrogen receptor and/or progesterone receptor > 1% by immunohistochemistry, AND HER2 negative unresectable breast cancer, with no overexpression by immunohistochemistry (IHC) or amplification by in-situ hybridization, are allowed to continue fulvestrant or an aromatase inhibitor (anastrozole, letrozole, exemestane) with AZD5363 if patient just progressed on this anti-estrogen therapy. Gonadotrophin releasing hormone (GnRH) agonists (such as leuprolide or goserelin) are allowed. For instance, if the last treatment was letrozole plus goserelin, the patient is allowed to continue the letrozole plus goserelin with AZD5363
- NOTE: Selective estrogen receptor modulators (SERMs), such as tamoxifen or toremifene, are not allowed, given concerns about CYPD26 and CYP3A4 metabolism, respectively
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 with diabetes or risk for hyperglycemia are eligible. Patients with diabetes mellitus may enter the study unless any of the following exclusion criteria are fulfilled:
- Baseline fasting glucose value of > 8.9 mmol/L or 160 mg/dL (fasting is defined as no calorific intake for at least 8 hours)
- Insulin required for routine diabetic management and control
- More than two oral hypoglycemic medications required for routine diabetic management and control

Exclusion Criteria:

Patients must not have known hypersensitivity to AZD5363 or compounds of similar chemical or biologic composition
Patients with known KRAS, NRAS, HRAS, or BRAF mutations are not eligible for this protocol, as these mutations may lead to limited response due to resistance
Patients may not have received treatment with another inhibitor of PI3K, AKT or mTOR in the neoadjuvant, adjuvant or metastatic setting with the exception of FDA approved rapalogs. Patients with metastatic cancer, who received PI3K/AKT/mTOR inhibitors on short preoperative window trials (treatment for 4 weeks or less) will be eligible if the treatment was over 6 months prior to registration
Patients may not have received strong inhibitors or potent inducers or substrates of CYP3A4 or substrates of CYP2D6 within 2 weeks before the first dose of study treatment (3 weeks for St John's Wort)

Sites / Locations

ECOG-ACRIN Cancer Research Group

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (capivasertib)

Arm Description

Patients receive capivasertib PO BID on days 1-4, 8-11, 15-18, and 22-25. 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 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

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. 6 month PFS rate was estimated using the Kaplan-Meier method, which can provide a point estimate for any specific time point.

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

NCT ID

NCT04439123

First Posted

June 18, 2020

Last Updated

June 6, 2023

Sponsor

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT04439123

Brief Title

Testing AZD5363 as a Potential Targeted Treatment in Cancers With AKT Genetic Changes (MATCH-Subprotocol Y)

Official Title

MATCH Treatment Subprotocol Y: AZD5363 in Patients With Tumors With AKT Mutations

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

May 31, 2016 (Actual)

Primary Completion Date

November 8, 2019 (Actual)

Study Completion Date

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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 AZD5363 in patients whose cancer has a genetic change called AKT mutation. AZD5363 may block AKT, which is a protein needed for cancer cell growth. Researchers hope to learn if AZD5363 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 capivasertib (AZD5363) orally (PO) twice daily (BID) on days 1-4, 8-11, 15-18, and 22-25. 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.

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 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment (capivasertib)

Arm Type

Experimental

Arm Description

Patients receive capivasertib PO BID on days 1-4, 8-11, 15-18, and 22-25. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Intervention Type

Drug

Intervention Name(s)

Capivasertib

Other Intervention Name(s)

AZD5363

Intervention Description

Given PO

Primary Outcome Measure Information:

Title

Overall Response Rate (ORR)

Description

Time Frame

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 Outcome Measure Information:

Title

6-month Progression-free Survival (PFS) Rate

Description

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 rate is determined

Title

Progression Free Survival (PFS)

Description

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

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 an AKT mutation as determined via the MATCH Master Protocol Patients with hormone receptor positive, defined as estrogen receptor and/or progesterone receptor > 1% by immunohistochemistry, AND HER2 negative unresectable breast cancer, with no overexpression by immunohistochemistry (IHC) or amplification by in-situ hybridization, are allowed to continue fulvestrant or an aromatase inhibitor (anastrozole, letrozole, exemestane) with AZD5363 if patient just progressed on this anti-estrogen therapy. Gonadotrophin releasing hormone (GnRH) agonists (such as leuprolide or goserelin) are allowed. For instance, if the last treatment was letrozole plus goserelin, the patient is allowed to continue the letrozole plus goserelin with AZD5363 NOTE: Selective estrogen receptor modulators (SERMs), such as tamoxifen or toremifene, are not allowed, given concerns about CYPD26 and CYP3A4 metabolism, respectively 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 with diabetes or risk for hyperglycemia are eligible. Patients with diabetes mellitus may enter the study unless any of the following exclusion criteria are fulfilled: Baseline fasting glucose value of > 8.9 mmol/L or 160 mg/dL (fasting is defined as no calorific intake for at least 8 hours) Insulin required for routine diabetic management and control More than two oral hypoglycemic medications required for routine diabetic management and control Exclusion Criteria: Patients must not have known hypersensitivity to AZD5363 or compounds of similar chemical or biologic composition Patients with known KRAS, NRAS, HRAS, or BRAF mutations are not eligible for this protocol, as these mutations may lead to limited response due to resistance Patients may not have received treatment with another inhibitor of PI3K, AKT or mTOR in the neoadjuvant, adjuvant or metastatic setting with the exception of FDA approved rapalogs. Patients with metastatic cancer, who received PI3K/AKT/mTOR inhibitors on short preoperative window trials (treatment for 4 weeks or less) will be eligible if the treatment was over 6 months prior to registration Patients may not have received strong inhibitors or potent inducers or substrates of CYP3A4 or substrates of CYP2D6 within 2 weeks before the first dose of study treatment (3 weeks for St John's Wort)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Kevin M Kalinsky

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

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Testing AZD5363 as a Potential Targeted Treatment in Cancers With AKT Genetic Changes (MATCH-Subprotocol Y)

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