NCT05554380

Study of Chemotherapy Plus Ipatasertib for People With Solid Tumors With PTEN/AKT Mutations, A ComboMATCH Treatment Trial

Phase 2 Study of Paclitaxel (NSC #673089) + Ipatasertib (NSC #781451) in Taxane-Refractory Participants With PTEN/AKT-Altered Advanced Non-Breast Solid Tumors: A ComboMATCH Treatment Trial

• Status: Suspended
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 33 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II ComboMATCH treatment trial tests the usual treatment of chemotherapy (paclitaxel) plus ipatasertib in patients with solid tumor cancers that that cannot be removed by surgery (unresectable), has spread to nearby tissue or lymph nodes (locally advanced) or from where it first started (primary site) to other places in the body (metastatic), and has PTEN and AKT genetic changes. Chemotherapy drugs, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Targeted therapy, such as Ipatasertib, may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. The addition of ipatasertib to paclitaxel in solid tumors with PTEN and AKT genetic changes could increase the percentage of tumors that shrink as well as lengthen the time that the tumors remain stable (without progression). Researchers hope to learn if paclitaxel plus ipatasertib will shrink this type of cancer or stop its growth.

Detailed description

PRIMARY OBJECTIVE: I. To assess the overall response rate (ORR) (confirmed and unconfirmed, complete, and partial) with the combination of paclitaxel plus ipatasertib in participants with advanced PTEN/AKT-altered non-breast solid tumors who have previously progressed on taxane-based therapy SECONDARY OBJECTIVES: I. To assess the progression-free survival (PFS) in the study population. II. To assess the duration of response (DoR) in participants who respond to treatment. III. To assess the overall survival (OS) in the study population. IV. To evaluate the frequency and severity of toxicities related to the combination therapy. V. Collect tissue and provide it to the ComboMATCH Registration protocol to assess concordance between the diagnostic tumor mutation profile generated by the designated laboratories, the pre-treatment biopsy mutation profile, and the pre-treatment circulating tumor deoxyribonucleic acid (ctDNA) mutation profile from plasma, as described in ComboMATCH Registration protocol. For this treatment substudy, the outcome objective will be to report the proportion of cases providing sufficient tissue for that integrated scientific activity in the ComboMATCH Registration protocol. TRANSLATIONAL MEDICINE OBJECTIVES: I. To conduct whole exome sequencing (WES) and ribonucleic acid (RNA) sequencing (RNAseq) analysis of tumors at baseline (mandatory), as well as PTEN expression analysis of tumors at baseline (2nd priority after nucleic acid for WES and RNAseq). II. To explore changes in plasma PTEN/AKT mutation allelic burden and other molecular findings at baseline (mandatory) and upon progression (optional) using ctDNA and correlate changes with response/resistance to therapy. III. To perform comprehensive protein expression and function analysis on fresh frozen specimens (optional) collected at baseline and at progression to assess determinants of response and resistance to therapy. OUTLINE: Patients receive paclitaxel intravenously (IV) on days 1, 8, and 15 and ipatasertib orally (PO) on days 1-21 of each cycle. Treatment repeats every 28 days for up to 35 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a computed tomography (CT) or magnetic resonance imaging (MRI) and blood collection throughout the trial. Patients also undergo a tumor biopsy during screening and optionally during follow-up. After completion of study treatment, patients are followed until death or 3 years after registration, whichever occurs first.

Conditions

• Locally Advanced Malignant Solid Neoplasm
• Metastatic Malignant Solid Neoplasm
• Unresectable Malignant Solid Neoplasm

Interventions

Type	Name	Description
PROCEDURE	Biopsy Procedure	Undergo tumor biopsy
PROCEDURE	Biospecimen Collection	Undergo blood collection
PROCEDURE	Computed Tomography	Undergo CT scan
DRUG	Ipatasertib	Given PO
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
DRUG	Paclitaxel	Given IV

Timeline

• Start date: 2023-09-22
• Primary completion: 2026-08-31
• Completion: 2026-08-31
• First posted: 2022-09-26
• Last updated: 2026-04-13

Locations

210 sites across 2 countries: United States, Puerto Rico

Regulatory

• FDA-regulated drug study