Testing Ipatasertib as Potentially Targeted Treatment in Cancers With AKT Genetic Changes (MATCH - Subprotocol Z1K)

NCT ID: NCT06400251

Last Updated: 2025-11-20

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

35 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-08-08

Study Completion Date

2025-12-31

Brief Summary

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This phase II MATCH treatment trial tests how well ipatasertib works in treating patients with cancer that has certain genetic changes called AKT mutations. Ipatasertib is in a class of medications called protein kinase B (AKT) inhibitors. It may stop the growth of cancer cells and may kill them.

Detailed Description

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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 ipatasertib 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. Additionally, patients undergo computed tomography (CT) or magnetic resonance imaging (MRI) during screening and on study, as well as during follow-up as clinically necessary. Patients undergo biopsies and blood sample collection on study.

After completion of study treatment, patients are followed 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

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Advanced Lymphoma Advanced Malignant Solid Neoplasm Refractory Lymphoma Refractory Malignant Solid Neoplasm Refractory Multiple Myeloma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (ipatasertib)

Patients receive ipatasertib 400 mg PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT or MRI during screening and on study, as well as during follow-up as clinically necessary. Patients undergo biopsies and blood sample collection on study.

Group Type EXPERIMENTAL

Biopsy Procedure

Intervention Type PROCEDURE

Undergo biopsy

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Computed Tomography

Intervention Type PROCEDURE

Undergo CT scan

Ipatasertib

Intervention Type DRUG

Given PO

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Interventions

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Biopsy Procedure

Undergo biopsy

Intervention Type PROCEDURE

Biospecimen Collection

Undergo blood sample collection

Intervention Type PROCEDURE

Computed Tomography

Undergo CT scan

Intervention Type PROCEDURE

Ipatasertib

Given PO

Intervention Type DRUG

Magnetic Resonance Imaging

Undergo MRI

Intervention Type PROCEDURE

Other Intervention Names

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Biopsy BIOPSY_TYPE Bx Biological Sample Collection Biospecimen Collected Specimen Collection CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized axial tomography (procedure) Computerized Tomography Computerized Tomography (CT) scan CT CT Scan Diagnostic CAT Scan Diagnostic CAT Scan Service Type tomography GDC 0068 GDC-0068 GDC0068 RG 7440 RG-7440 RG7440 Magnetic Resonance Magnetic Resonance Imaging (MRI) Magnetic resonance imaging (procedure) Magnetic Resonance Imaging Scan Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance MR MR Imaging MRI MRI Scan MRIs NMR Imaging NMRI Nuclear Magnetic Resonance Imaging sMRI Structural MRI

Eligibility Criteria

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Inclusion Criteria

* Patients must have met applicable eligibility criteria in the Master MATCH Protocol EAY131/ NCI-2015-00054 prior to registration to treatment subprotocol
* Patients must have an AKT mutation as determined via the MATCH Master Protocol
* Patients with breast cancer are excluded
* Patients with castration-resistant prostate cancer should maintain castrate levels of testosterone (i.e., with gonadotropin-releasing hormone (GnRH) agonists or through surgical castration). Patients are allowed to continue abiraterone acetate/prednisone with Ipatasertib if the patient just progressed on abiraterone acetate/prednisone
* Patients must not have known hypersensitivity to Ipatasertib 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

Exclusion Criteria

* 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)
* Patients not on a stable dose of oral hypoglycemic medication for \>= 4 weeks and appropriate diet
* Insulin required for routine diabetic management and control
* More than two oral hypoglycemic medications required for routine diabetic management and control
* Glycosylated hemoglobin (hemoglobin A1C) \>= 7.5%
* Prior PI3K and mTOR inhibitors are allowed, including in the metastatic setting. Prior AKT inhibitors are excluded
* Patients with a history of inflammatory bowel diseases (Crohn's disease and ulcerative colitis) or active diverticulitis are not eligible
* Patients may not have received strong inhibitors or potent inducers or substrates of CYP3A4/5 within 2 weeks before the first dose of study treatment (3 weeks for St John's wort)
* In addition to the patient contraception requirements outlined in EAY131 MATCH Master Protocol, male patients must also refrain from donating sperm for the duration of study participation, and for 4 months after completion of study
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Kevin M Kalinsky

Role: PRINCIPAL_INVESTIGATOR

ECOG-ACRIN Cancer Research Group

Locations

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ECOG-ACRIN Cancer Research Group

Philadelphia, Pennsylvania, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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NCI-2024-01194

Identifier Type: REGISTRY

Identifier Source: secondary_id

EAY131-Z1K

Identifier Type: OTHER

Identifier Source: secondary_id

EAY131-Z1K

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA180820

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2024-01194

Identifier Type: -

Identifier Source: org_study_id

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