Ipat-Lung: Ipatasertib and Docetaxel in Metastatic NSCLC Patients Who Have Failed 1st Line Immunotherapy

Sponsor

Jun Zhang, MD, PhD (Other)

Overall Status

Recruiting

CT.gov ID

NCT04467801

Collaborator

University of Iowa (Other), University of Kentucky (Other)

Enrollment

Locations

Arm

46.6

Anticipated Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

For metastatic/advanced NSCLC patients who do not have targetable mutations, either immunotherapy targeting the programmed death-1 and its ligand (PD-1/L1) pathway alone or in combination with platinum doublet chemotherapy is now a standard of care. However, still about half of the patients do not benefit due to treatment resistance. It is therefore critically important to find novel therapies and combinations to benefit patients who have failed or are intolerant to 1st line immunotherapy.

This study hypothesizes that ipatasertib in combination with taxane (e.g. docetaxel) can be an effective strategy. Ipatasertib is a novel adenosine triphosphate (ATP)-competitive inhibitor that has demonstrated robust and selective targeting of protein kinase B (PKB, also known as AKT) in cancer patients. Importantly, evidence from preclinical studies has demonstrated that AKT inhibitors (e.g. ipatasertib) can enhance the therapeutic effect of chemotherapy as well as immunotherapy via modulating Phosphatidylinositol 3-kinase (PI3'K)-AKT activity.

Condition or Disease	Intervention/Treatment	Phase
NSCLC Stage IV NSCLC Stage IIIB	Drug: Ipatasertib	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Multi-center Phase II Study of Ipatasertib in Combination With Docetaxel in Metastatic/Advanced NSCLC Patients Who Have Failed or Are Intolerant to 1st Line Immunotherapy (Ipat-Lung)

Actual Study Start Date :

Sep 14, 2021

Anticipated Primary Completion Date :

Aug 1, 2023

Anticipated Study Completion Date :

Aug 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment Ipatasertib, 400 mg once daily, Oral, Days 1-14 of each 21 day cycle (2 weeks on and 1 week off). Docetaxel, 75 mg/m2, Intra-venous, Day 1 of each 21 day cycle.	Drug: Ipatasertib Ipatasertib is a novel ATP-competitive inhibitor. It is taken by mouth once daily.

Arm

Intervention/Treatment

Experimental: Treatment

Ipatasertib, 400 mg once daily, Oral, Days 1-14 of each 21 day cycle (2 weeks on and 1 week off). Docetaxel, 75 mg/m2, Intra-venous, Day 1 of each 21 day cycle.

Drug: Ipatasertib

Ipatasertib is a novel ATP-competitive inhibitor. It is taken by mouth once daily.

Outcome Measures

Primary Outcome Measures

Progression Free Survival [up to 12 months]
RECIST 1.1

Secondary Outcome Measures

Number of adverse events experienced by participants receiving treatment with ipatasertib in combination with docetaxel [At cycle 1day 8 (each cycle is 21 days) up to 2 months (60 days) after End of treatment]
CTCAE Version 5.0
Overall Response Rate [every 6 weeks up to 12 months]
RECIST 1.1
Overall Survival [Cycle 1day 1 (each cycle is 21 days) to up to 12 months after end of treatment]
Medical record

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Ability of participant OR Legally Authorized Representative (LAR) to understand this study, and participant or LAR willingness to sign a written informed consent
Life expectancy ≥12 weeks
Males and females age ≥ 18 years
Allowable type and amount of prior therapy:

First line anti-Programmed death receptor and ligand (PD1/PD-L1), either single agent or in combination with chemotherapy

Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
Measurable disease per RECIST version 1.1
Diagnoses of advanced/metastatic NSCLC and have failed or are intolerant to 1st line anti-PD1/PD-L1, either single agent or in combination with chemotherapy, and have either exhausted or decline or not be candidates for all available standard of care therapies.
Adequate organ function
Women of child-bearing potential and men with partners of child-bearing potential must agree to practice sexual abstinence, or to use an acceptable form of contraception for the duration of study participation, and for 90 days following completion of therapy
Men of child-bearing potential must agree not to donate sperm while on this study and for 90 days after their last study treatment

Exclusion Criteria:

Is not concurrent enrolled in another clinical study, unless it is an observational (non-interventional) clinical study or if the participant is in the follow-up period of an interventional study
Is not currently on or is not anticipated to use other investigational agents within 14 days prior to and while participating in this study
Does not have mixed small cell and non-small cell lung cancer histology
Does not have any unresolved toxicity CTCAE >Grade 2 from the prior 1st immunotherapy. Patients with irreversible toxicity that is not reasonably expected to be exacerbated by study drug may be included
Patients who have targetable mutations that qualify for targeted therapy (e.g. mutations of epidermal growth factor receptor (EGFR), serine/ threonine- protein kinase (BRAF), anaplastic lymphoma kinase (ALK), tyrosine- protein kinase (ROS1), neurotrophic receptor tyrosine kinase (NTRAK)) will be excluded from this study
Is not on concomitant therapy intended for the treatment of cancer (including, but not limited to, chemotherapy, hormonal therapy, immunotherapy, radiotherapy, and herbal therapy) for 14 days prior to starting study treatment, depending on the agent and during study treatment, until disease progression is documented and the patient has discontinued study treatment, with the exception of palliative radiotherapy and local therapy per PI discretion
Does not chronically use a strong cytochrome P4503A4 (CYP3A4/5) inhibitor or inducer, or sensitive CYP3A substrates with a narrow therapeutic window
Has not had recent major surgery within 4 weeks prior to entry into the study (excluding the placement of vascular access) that would prevent administration of study drug
Does not have uncontrolled systemic disease
Does not have uncontrolled brain metastasis
Does not have history of allergy to taxanes
Does not have history of leptomeningeal carcinomatosis
Does not have recent history of myocardial infarction (MI) or symptomatic coronary artery disease within 6 months of screening
Is not receiving active therapy for HIV, hepatitis B or hepatitis C
Does not have history of malabsorption syndrome or other condition that would interfere with enteral absorption or results in the inability or unwillingness to swallow pills
Does not have history of Type I or Type II diabetes mellitus requiring insulin (Patients who are on a stable dose of oral diabetes medication greater than or equal to 2 weeks prior to initiation of study treatment
Does not have Grade greater than or equal to 2 uncontrolled or untreated hypercholesterolemia or hypertriglyceridemia
Does not have history of or active inflammatory bowel disease (e.g., Crohn's disease and ulcerative colitis) or active bowel inflammation (e.g., diverticulitis)
Does not have active pneumonitis
Does not have history of lung disease: interstitial lung disease, idiopathic pulmonary fibrosis, cystic fibrosis, Aspergillosis, active tuberculosis, or history of opportunistic infections
Does not have uncontrolled pleural effusion/pericardial effusion/or ascites as determined by the investigator
Does not have active ventricular arrhythmia requiring medication
Does not have psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the patient to give written informed consent
Is not pregnant, breast feeding or planning to become pregnant while receiving study treatment or for less than 90 days after the last dose of study treatment
For males with partners of childbearing potential, is not planning to father a child or donate sperm while receiving study treatment or for less than 90 days after the last dose of study treatment
Does not have any condition that, in the opinion of the investigator, would interfere with evaluation or interpretation of patient safety or study results

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The University of Kansas Cancer Center (KUCC)	Fairway	Kansas	United States	66205
2	The University of Kansas Cancer Center, Westwood Campus	Kansas City	Kansas	United States	66205
3	The University of Kansas Cancer Center, Overland Park Clinic	Overland Park	Kansas	United States	66210
4	The University of Kansas Cancer Center, North Clinic	Kansas City	Missouri	United States	64154
5	The University of Kansas Cancer Center, Lee's Summit Clinic	Lee's Summit	Missouri	United States	64064

Sponsors and Collaborators

Jun Zhang, MD, PhD
University of Iowa
University of Kentucky

Investigators

Principal Investigator: Jun Zhang, MD, PhD, The University of Kansas

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Jun Zhang, MD, PhD, MD, PhD, University of Kansas Medical Center

ClinicalTrials.gov Identifier:

NCT04467801

Other Study ID Numbers:

IIT-2019-IpatTax

First Posted:

Jul 13, 2020

Last Update Posted:

Dec 1, 2021

Last Verified:

Nov 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Jun Zhang, MD, PhD, MD, PhD, University of Kansas Medical Center

Advanced/metastatic NSCLC

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung

Study Results

No Results Posted as of Dec 1, 2021