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Poziotinib in EGFR Exon 20 Mutant Advanced NSCLC

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ClinicalTrials.gov Identifier: NCT03066206
Recruitment Status : Recruiting
First Posted : February 28, 2017
Last Update Posted : June 27, 2022
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Spectrum Pharmaceuticals, Inc
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Tracking Information
First Submitted Date  ICMJE February 23, 2017
First Posted Date  ICMJE February 28, 2017
Last Update Posted Date June 27, 2022
Actual Study Start Date  ICMJE March 17, 2017
Estimated Primary Completion Date March 1, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 14, 2019)
  • Objective response rate a in patients with estimated glomerular filtration rate (EGFR) exon 20 mutant non-small Cell Lung Cancer (NSCLC) (Cohort 1) [ Time Frame: Up to 4 years ]
    According to Response Evaluation Criteria in Solid Tumors 1.1 criteria.
  • Objective response rate a in patients with human epidermal growth factor receptor 2 (HER2) exon 20 mutant non-small Cell Lung Cancer (NSCLC) (Cohort 2) [ Time Frame: Up to 4 years ]
    According to Response Evaluation Criteria in Solid Tumors 1.1 criteria.
Original Primary Outcome Measures  ICMJE
 (submitted: February 23, 2017)
  • Objective Response Rate (ORR) to Poziotinib in Non-Small Cell Lung Cancer (NSCLC) Participants with EGFR Exon 20 Mutations [ Time Frame: 3 months ]
    ORR calculated as the percent of patients whose best confirmed response is complete response (CR, defined as disappearance of all target lesions) or partial response (PR, defined as at least a 30% decrease in the sum of longest diameter (LD) of target lesions taking as reference the baseline sum LD). ORR assessed according to RECIST 1.1 criteria.
  • Adverse Events of Poziotinib in Non-Small Cell Lung Cancer (NSCLC) Participants with EGFR Exon 20 Mutations [ Time Frame: 1 month ]
    Adverse events assessed by Common Terminology Criteria for Adverse Events version 4.03.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 14, 2019)
  • Disease control rate (complete response + partial response + stable disease) of poziotinb in cohort 1 and 2, analyzed independently [ Time Frame: Up to 4 years ]
    Will be estimated along with 95% confidence intervals.
  • Progression free survival of poziotinb in cohort 1 and 2, analyzed independently [ Time Frame: Up to 4 years ]
    Will be estimated using the Kaplan-Meier method and the comparison between or among patient's characteristic groups will be evaluated by log-rank test. The Cox regression model may be applied to assess the effect of covariates of interest on progression free survival.
  • Overall survival of poziotinb in cohort 1 and 2, analyzed independently [ Time Frame: Up to 4 years ]
    Will be estimated using the Kaplan-Meier method and the comparison between or among patient's characteristic groups will be evaluated by log-rank test. The Cox regression model may be applied to assess the effect of covariates of interest on overall survival.
  • Duration of response of poziotinb in cohort 1 and 2, analyzed independently [ Time Frame: Up to 4 years ]
    Duration of response will be measured.
  • Incidence of adverse events [ Time Frame: Up to 4 years ]
    Assessed by Common Terminology Criteria for Adverse Events version 4.03. Toxicity data will be summarized by frequency tables.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 23, 2017)
Disease Control Rate of Poziotinib in Non-Small Cell Lung Cancer (NSCLC) Participants with EGFR Exon 20 Mutations [ Time Frame: 8 weeks after initiation of treatment. ]
Disease control rate defined as the percentage of patients have either a partial response (PR), a complete response (CR), or stable disease (SD) lasting at least 8 weeks after initiation of treatment. Response assessed by RECIST 1.1 criteria.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Poziotinib in EGFR Exon 20 Mutant Advanced NSCLC
Official Title  ICMJE A Phase II Study of Poziotinib in EGFR or HER2 Mutant Advanced Solid Tumors
Brief Summary This phase II trial studies how well poziotinib works in treating patients with non-small lung cancer with an EGFR or HER2 exon 20 mutation that is stage IV or has come back (recurrent). Poziotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth..
Detailed Description

PRIMARY OBJECTIVES:

I. To assess the objective response rate (ORR) to poziotinib according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria in non-small cell lung cancer (NSCLC) with EGFR exon 20 mutations.

II. Assess the objective response rate (ORR) to poziotinib according to RECIST 1.1 criteria in NSCLC with HER2 (ErBB2) exon 20 mutations.

III. Assess the objective response rate (ORR) to poziotinib according to RECIST 1.1 criteria in advanced solid tumors with EGFR exon 20 or HER2 exon 20 mutations.

IV. Assess the objective response rate (ORR) to poziotinib according to RECIST 1.1 criteria in advanced solid tumors with HER2 exon 19 mutations ORR will be calculated as the percent of patients whose best confirmed response is complete response (CR, defined as disappearance of all target lesions) or partial response (PR, defined as at least a 30% decrease in the sum of longest diameter [LD] of target lesions, taking as reference the baseline sum LD).

SECONDARY OBJECTIVES:

I. Disease control rate (complete response + partial response + stable response) of poziotinb in cohort 1 and 2, analyzed independently.

II. Progression free survival of poziotinb in cohort 1 and 2, analyzed independently.

III. Overall survival of poziotinb in cohort 1 and 2, analyzed independently. IV. Duration of response of poziotinb in cohort 1 and 2, analyzed independently.

V. Safety and toxicity.

EXPLORATORY OBJECTIVES:

I. To assess molecular markers associated with resistance and response to poziotinib, including secondary mutations.

OUTLINE:

Patients receive poziotinib orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 6 months thereafter.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • EGFR Exon 20 Mutation
  • ERBB2 Gene Mutation
  • Recurrent Lung Non-Small Cell Carcinoma
  • Stage IV Non-Small Cell Lung Cancer AJCC v7
Intervention  ICMJE Drug: Poziotinib
Given PO
Other Names:
  • HM781-36B
  • NOV120101
Study Arms  ICMJE Experimental: Treatment (poziotinib)
Patients receive poziotinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention: Drug: Poziotinib
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 19, 2017)
80
Original Estimated Enrollment  ICMJE
 (submitted: February 23, 2017)
30
Estimated Study Completion Date  ICMJE March 1, 2023
Estimated Primary Completion Date March 1, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically or cytologically confirmed stage IV or recurrent solid tumor not amenable to curative intent therapy
  • Cohort 1 specific inclusion criteria: NSCLC with documented EGFR exon 20 mutation by one of the following Clinical Laboratory Improvement Act (CLIA) certified tests: OncoMine Comprehensive Assay (OCA), Guardant360 Assay (using plasma), or FoundationOne Assay or by a Food and Drug Administration (FDA) approved device using cobas EGFR mutation test version (v)2 or therascreen EGFR RGQ PCt kit; Mutations include D770_N771insSVD, D770_N771insNPG, V769_D770insASV, H773_V774insNPH, or any other exon 20 in-frame insertion or point mutation excluding T790M
  • Cohort 2 specific inclusion criteria: NSCLC with documented HER2 exon 20 mutation by a CLIA certified tests: Oncomine Comprehensive Assay (OCA), Guardant360 Assay (using plasma), or FoundationOne Assay; eligible mutations include A775_G776insYVMA, G776_V777insVC, or P780_Y781insGSP, or any other in-frame exon 20 insertion mutation or point mutation including, but not limited to, L755S, G776V, and V777L
  • Cohort 3 specific inclusion criteria: NSCLC with documented EGFR exon 20 mutation (excluding T790M) by one of the following CLIA certified tests: OncoMine Comprehensive Assay (OCA), Guardant360 Assay (using plasma), or FoundationOne Assay or by an FDA approved device using cobas EGFR mutation test v2 or therascreen EGFR RGQ PCt kit; mutations include D770_N771insSVD, D770_N771insNPG, V769_D770insASV, H773_V774insNPH, or any other exon 20 in-frame insertion or point mutation excluding T790M
  • Cohort 4 specific inclusion criteria: solid tumor (excluding NSCLC) harboring EGFR or HER2 exon 20 mutations documented by one of the following CLIA certified tests: Oncomine Comprehensive Assay (OCA), Guardant360 Assay (using plasma), or FoundationOne Assay
  • Cohort 5 specific inclusion criteria: solid tumor harboring HER2 exon 19 mutation documented by one of the following CLIA certified tests: Oncomine Comprehensive Assay (OCA), Guardant360 Assay (using plasma), or FoundationOne Assay
  • Patients must have exhausted all FDA-approved standard of care options for locally advanced or metastatic disease, or are ineligible for FDA-approved standard of care options, or refusing to receive FDA-approved standard of care options. Previously untreated patients are allowed only in cohort 1 and 3 and are eligible only if EGFR Exon 20 mutation is confirmed using an FDA approved device/test such as cobas EGFR Mutation Test v2, therascreen EGFR RGQ PCR Kit or other FDA tests prior to study enrollment
  • Patient has adequate tumor tissue obtained from a biopsy or surgical procedure to enable molecular profiling for retrospective central laboratory confirmation of the mutation. If tissue is not available, the patient must have biopsy accessible disease and must be willing to undergo a biopsy prior to the study
  • Measurable disease by RECIST 1.1
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Ability to take pills by mouth
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Hemoglobin >= 9.0 g/dL
  • Total bilirubin =< 2 x upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 institutional upper limit of normal of =< 5 x ULN if liver metastases are present
  • Alkaline phosphatase =< 2.5 institutional upper limit of normal of =< 5 x ULN if liver metastases are present
  • Creatinine clearance >= 50 mL/min/1.73 m^2 by Cockcroft-Gault equation
  • Brain metastases are allowed, as long as they are stable and do not require treatment with anticonvulsants or escalating doses of steroids
  • Females of childbearing potential must have a negative serum or urine pregnancy test and must agree to use adequate contraception for the duration of the study and six months after; adequate contraception methods include: birth control pills (e.g. combined oral contraceptive pill), barrier protection (e.g. condom plus spermicide, cervical/vault cap or intrauterine device), and abstinence; females of childbearing potential are defined as those who are not surgically sterile (i.e., bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or postmenopausal (defined as 12 months with no menses without an alternative medical cause); women will be considered post-menopausal if they have been amenorrheic for the past 12 months without an alternative medical cause
  • The following age-specific requirements must also apply:

    • Women < 50 years old: they would be considered post-menopausal if they have been amenorrheic for the past 12 months or more following cessation of exogenous hormonal treatments; the levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) must also be in the post-menopausal range (as per the institution)
    • Women >= 50 years old: they would be considered post-menopausal if they have been amenorrheic for the past 12 months or more following cessation of all exogenous hormonal treatments, or have had radiation-induced oophorectomy with the last menses > 1 year ago, or have had chemotherapy-induced menopause with > 1 year interval since last menses, or have had surgical sterilization by either bilateral oophorectomy or hysterectomy
  • Non-sterilized males who are sexually active with a female partner of childbearing potential must use adequate contraception for the duration of the study and 90 days after the last dose of study medication; adequate contraception methods include: birth control pills (e.g. combined oral contraceptive pill), barrier protection (e.g. condom plus spermicide, cervical/vault cap or intrauterine device), and abstinence
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • EGFR T790M mutation or any other acquired EGFR exon 20 mutation; patients with coexisting primary EGFR exon 20 and T790M mutations are eligible
  • Have received or are receiving an investigational medicinal product (IMP) or other systemic anticancer treatment within 2 weeks prior to the first dose of study treatment
  • Any concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment
  • Have known or suspected brain metastases or spinal cord compression, unless the condition has been asymptomatic, has been treated with surgery and/or radiation, and has been stable without requiring escalating corticosteroids nor anti-convulsant medications for at least 4 weeks prior to the first dose of study medication
  • Known hypersensitivity to poziotinib or history of allergic reactions attributed to compounds of similar chemical or biologic composition to poziotinib
  • Cardiac conditions as follows:

    • Patient has a history of congestive heart failure (CHF) class III/IV according to the New York Heart Association (NYHA) Functional Classification or serious cardiac arrhythmias requiring treatment
    • Patient has a cardiac ejection fraction < 50% by either echocardiogram or multi-gated acquisition (MUGA) scan
  • Have any unresolved chronic toxicity with Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 grade >= 2, from previous anticancer therapy, except for alopecia
  • Patient is unable to take drugs orally due to disorders or diseases that may affect gastrointestinal function, such as inflammatory bowel diseases (e.g., Crohn's disease, ulcerative colitis) or malabsorption syndrome, or procedures that may affect gastrointestinal function, such as gastrectomy, enterectomy, or colectomy
  • Have any condition or illness that, in the opinion of the investigator, might compromise patient safety or interfere with the evaluation of the safety of the drug
  • Pregnant or breastfeeding women
  • History of another primary malignancy within 2 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
  • Recent major surgery within 4 weeks prior to starting study treatment, with the exception of surgical placement for vascular access
  • Male or female patients of reproductive potential who are not employing an adequate method of birth control; adequate contraception methods include: birth control pills (e.g. combined oral contraceptive pill), barrier protection (e.g. condom plus spermicide cervical/vault cap or intrauterine device), and abstinence
  • Uncontrolled intercurrent illness including, but not limited to, uncompensated respiratory, cardiac, hepatic, or renal disease, active infection (including hepatitis B, hepatitis C, human immunodeficiency virus [HIV], and active clinical tuberculosis), or renal transplant; ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, or psychiatric illness/social situations that would limit compliance with study requirements
  • Active bleeding disorders.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Yasir Y. Elamin, MD 713-792-6363 yyelamin@mdanderson.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03066206
Other Study ID Numbers  ICMJE 2016-0783
NCI-2017-00831 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2016-0783 ( Other Identifier: M D Anderson Cancer Center )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party M.D. Anderson Cancer Center
Original Responsible Party Same as current
Current Study Sponsor  ICMJE M.D. Anderson Cancer Center
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE
  • National Cancer Institute (NCI)
  • Spectrum Pharmaceuticals, Inc
Investigators  ICMJE
Principal Investigator: Yasir Y Elamin M.D. Anderson Cancer Center
PRS Account M.D. Anderson Cancer Center
Verification Date June 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP