Study of Poziotinib in Japanese Patients With NSCLC

NSCLC Clinical Trial

Official title:

A Phase 1/2 Dose Finding Study of Poziotinib in Japanese Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04402008
• Other study ID #: SPI-POZ-104
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: June 26, 2020
• Est. completion date: May 15, 2023

Study information

• Verified date: July 2023
• Source: Spectrum Pharmaceuticals, Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A Phase 1/2, open-label, multicenter study to determine dose, tolerability, safety and efficacy of poziotinib in Japanese patients non-small cell lung cancer (NSCLC).

Description:

This is a Phase 1/2, open-label, multicenter study in Japanese patients with locally advanced or metastatic NSCLC. This study will be conducted in two parts. Phase 1 is designed to observe the maximum tolerated dose (MTD) or maximum administered dose (MAD) of poziotinib when administered once daily or twice daily. Phase 2 will evaluate the safety and efficacy of the dose determined in Phase 1. Study participation includes a 30 day screening period, up to 24 months of treatment, and long-term follow-up for a maximum of 24 months after discontinuation of study treatment.

Phase 1 will enroll up to 36 patients into a dose finding study with two parallel, randomized dose groups. Each group will undergo a dose-finding scheme using a 3+3 design with the assessment of dose-limiting toxicities (DLTs) at up to three dose levels. Patients will be randomized into once daily (QD) or twice daily (BID) dose groups. The DLT assessment will be conducted in the first cycle of treatment and therefore, poziotinib dose modifications are not permitted during this cycle. Patients will be hospitalized for the first 2 weeks.

Phase 2 will enroll 40 additional NSCLC patients with EGFR (20 patients) or HER2 (20 patients) exon 20 insertion mutations. Efficacy and safety of the dose and dosing regimen determined in Phase 1 will be evaluated. All patients will be treated in 28-day cycles for up to 24 months.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 42
• Est. completion date: May 15, 2023
• Est. primary completion date: February 15, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

Key Inclusion Criteria:

• Patient must be willing and capable of giving written Informed Consent, adhering to dosing and visit schedules, and meeting all study requirements

• Previously treated patient with histologically or cytologically confirmed (archival tissue accepted) locally advanced or metastatic non-small cell lung cancer (NSCLC) and is not a candidate for definitive therapy

• Phase 1: No test for mutational status is required

• Phase 2: Documented EGFR or HER2 exon 20 insertion mutations (including duplication mutations) in NSCLC patients

• Prior treatment status:

• Phase 1: Patient with refractory NSCLC to available standard therapies

• Phase 2: Progression after at least one systemic therapy for locally advanced or metastatic disease

• Patient has measurable NSCLC disease, as per the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). Metastatic lesions in bone, CNS, or in brain cannot be used for target lesions.

• Patient has recovered from prior systemic therapy for metastatic disease to Grade =1 for non-hematologic toxicities (except for Grade =2 peripheral neuropathy) and has adequate hematologic, hepatic, and renal function at Baseline

Key Exclusion Criteria:

• Patient is concurrently receiving chemotherapy, biologics, immunotherapy for cancer treatment; systemic anti-cancer treatment or investigational treatment should not be used within 2 weeks prior to Cycle 1, Day 1; local radiation therapy for bone pain may be allowed

• Patient has used strong inhibitors/inducers of CYP3A4 and CYP2D6 within 1 month prior to Cycle 1, Day 1

• Patient has had another primary malignancy within 3 years prior to starting study treatment, except for adequately treated basal or squamous cell carcinoma of the skin or cancer of the cervix in situ

• Patient is pregnant or breastfeeding

• Phase 2 : Patient has had previous treatment with poziotinib. The currently approved TKIs that are not considered to be exon 20 insertion-selective are permissible

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• NSCLC

Intervention

Drug:
• Poziotinib Once Daily Dosing
The poziotinib drug substance is a hydrochloride salt of poziotinib and is formulated as a tablet for oral administration.
• Poziotinib Twice Daily Dosing
The poziotinib drug substance is a hydrochloride salt of poziotinib and is formulated as a tablet for oral administration.
• Poziotinib Once Daily Dosing or Twice Daily Dosing as determined in Phase 1
The poziotinib drug substance is a hydrochloride salt of poziotinib and is formulated as a tablet for oral administration.

Locations

Country	Name	City	State
Japan	National Cancer Center East	Kashiwa	Chiba
Japan	Osaka City General Hospital	Miyakojima-ku	Osaka
Japan	Shizuoka Cancer Center	Sunto District	Shizuoka

Sponsors (1)

Lead Sponsor	Collaborator
Spectrum Pharmaceuticals, Inc

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Phase 2: Exploratory - Overall Survival	The number of days from the treatment start date to the date of death due to any cause.	2 years
Primary	Phase 1: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD)	MTD/MAD will be assessed based on the occurrence of defined dose-limiting toxicities (DLT) and all available safety information during first cycle of treatment.	28 Days
Primary	Phase 2: Objective Response Rate (ORR)	The proportion of patients who achieve Complete Response (CR) or Partial response (PR) by the best response from the first dose of poziotinib to the end of the study.	24 months
Secondary	Phase 2: Disease Control Rate (DCR)	The proportion of patients who achieve CR, PR, and Stable Disease (SD) by the best response from the first dose of poziotinib to the end of the study.	24 months
Secondary	Phase 2: Duration of Response (DoR)	The number of days from the date that measurement criteria are first met for CR or PR (whichever status is recorded first) until the first subsequent date that progressive disease or death is documented.	24 months
Secondary	Phase 2: Progression Free Survival (PFS)	The number of days from the treatment start date to the date of documented disease progression or death.	24 months