Title
Phase II Study of Paclitaxel (NSC #673089) + Ipatasertib (NSC #781451) In Taxane-Refractory Participants With AKT-Altered Advanced Non-Breast Solid Tumors (A ComboMATCH Treatment Trial)

Description
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 an AKT genetic change. 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 an AKT genetic change 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.

Objective
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 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 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.

Treatment Experimental: Treatment (paclitaxel, ipatasertib)
Patients receive paclitaxel IV and ipatasertib PO on study. Patients undergo a CT or MRI and blood collection throughout the trial. Patients also undergo a tumor biopsy during screening and follow-up.

Procedure: Biopsy
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

Key Eligibility For full study eligibility, see this study's ClinicalTrials.gov record.

Applicable Disease Sites
Anal; Any Site; Bladder; Brain/Central Nervous System; Cervix; Colon and Rectum; Endocrine cancers; Esophagus; Gastrointestinal cancers, other; Genitourinary cancers, other; Head and Neck; Ill-Defined Sites; Kidney; Liver; Lung; Melanoma/Skin cancer; Ovary; Pancreas; Prostate; Sarcoma; Stomach; Thyroid; Unknown Sites; Uterus

Participating Institutions
UW Health 1 S. Park Medical Center; UW Health University Hospital