Ipatasertib and Docetaxel in Metastatic NSCLC Patients Who Have Failed 1st Line Immunotherapy

NCT04467801 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: IIT-2019-IpatTax
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 5

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.

Conditions

NSCLC Stage IV; NSCLC Stage IIIB

Keywords

Advanced/metastatic NSCLC

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  RECIST 1.1

  up to 12 months

Secondary Outcomes (3)

• 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

• Overall Response Rate

  every 6 weeks up to 12 months

• Overall Survival

  Cycle 1day 1 (each cycle is 21 days) to up to 12 months after end of treatment

Study Arms (1)

Treatment

EXPERIMENTAL

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

Interventions

Ipatasertib DRUG

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

Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Jun Zhang, MD, PhD: lead
• University of Iowa: collaborator
• University of Kentucky: collaborator

Study Sites (5)

The University of Kansas Cancer Center (KUCC)

Fairway, Kansas, 66205, United States

RECRUITING

The University of Kansas Cancer Center, Westwood Campus

Kansas City, Kansas, 66205, United States

RECRUITING

The University of Kansas Cancer Center, Overland Park Clinic

Overland Park, Kansas, 66210, United States

ACTIVE NOT RECRUITING

The University of Kansas Cancer Center, North Clinic

Kansas City, Missouri, 64154, United States

ACTIVE NOT RECRUITING

The University of Kansas Cancer Center, Lee's Summit Clinic

Lee's Summit, Missouri, 64064, United States

ACTIVE NOT RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

ipatasertib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Jun Zhang, MD, PhD

  The University of Kansas

  PRINCIPAL INVESTIGATOR

Central Study Contacts

KUCC Navigator

CONTACT

9135883671; KUCC_Navigation@kumc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: June 15, 2020
• First Posted: July 13, 2020
• Study Start: September 14, 2021
• Primary Completion: August 1, 2024
• Study Completion: August 1, 2025
• Last Updated: November 7, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)