Clinical Trials /

Study of Poziotinib in Japanese Patients With NSCLC

NCT04402008

Description:

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).

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Poziotinib in Japanese Patients With NSCLC
  • 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 IDs

  • ORG STUDY ID: SPI-POZ-104
  • NCT ID: NCT04402008

Conditions

  • NSCLC

Interventions

DrugSynonymsArms
Poziotinib Once Daily DosingPhase 1: Once Daily Dosing
Poziotinib Twice Daily DosingPhase 1: Twice Daily Dosing
Poziotinib Once Daily Dosing or Twice Daily Dosing as determined in Phase 1Phase 2: Once Daily Dosing or Twice Daily Dosing

Purpose

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).

Detailed 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.
    

Trial Arms

NameTypeDescriptionInterventions
Phase 1: Once Daily DosingExperimentalDose finding at 8 mg, 12 mg, or 16 mg of poziotinib once daily in 28-day treatment cycles.
  • Poziotinib Once Daily Dosing
Phase 1: Twice Daily DosingExperimentalDose finding at 4 mg, 6 mg, or 8 mg of poziotinib twice daily in 28-day treatment cycles.
  • Poziotinib Twice Daily Dosing
Phase 2: Once Daily Dosing or Twice Daily DosingExperimentalOnce Daily or Twice Daily Dosing as determined in Phase 1 in 28-day treatment cycles. Cohort 1: EGFR exon 20 insertion mutations Cohort 2: HER2 exon 20 insertion mutations
  • Poziotinib Once Daily Dosing or Twice Daily Dosing as determined in Phase 1

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:20 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 1: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD)
Time Frame:28 Days
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Phase 2: Disease Control Rate (DCR)
Time Frame:24 months
Safety Issue:
Description: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.
Measure:Phase 2: Duration of Response (DoR)
Time Frame:24 months
Safety Issue:
Description: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.
Measure:Phase 2: Progression Free Survival (PFS)
Time Frame:24 months
Safety Issue:
Description:The number of days from the treatment start date to the date of documented disease progression or death.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Spectrum Pharmaceuticals, Inc

Trial Keywords

  • EGFR
  • HER2
  • Exon 20 insertion mutation

Last Updated

May 22, 2020