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Poziotinib in EGFR Exon 20 Mutant Advanced Non-Small Cell Lung Cancer (NSCLC) and HER2 Exon 20 Mutant NSCLC

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ClinicalTrials.gov Identifier: NCT03066206
Recruitment Status : Recruiting
First Posted : February 28, 2017
Last Update Posted : July 17, 2018
Sponsor:
Collaborators:
Lung Cancer Research Foundation
Spectrum Pharmaceuticals, Inc
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

The goal of this clinical research study is to learn if poziotinib can help to control EGFR-positive non-small cell lung cancer (NSCLC) that is locally advanced or metastatic (has spread). EGFR-positive NSCLC means that there is a mutation (a type of genetic change) on the EGFR gene.

The safety of poziotinib will also be studied.

This is an investigational study. Poziotinib is not FDA approved or commercially available. It is being used for research purposes only. The study doctor can explain how the study drug is designed to work.

Up to 80 participants will be enrolled in this study. All will take part at MD Anderson.


Condition or disease Intervention/treatment Phase
Malignant Neoplasm of Respiratory and Intrathoracic Organ Non-Small Cell Lung Cancer Drug: Poziotinib Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Poziotinib in EGFR Exon 20 Mutant Advanced Non-Small Cell Lung Cancer (NSCLC) and HER2 Exon 20 Mutant NSCLC
Actual Study Start Date : March 17, 2017
Estimated Primary Completion Date : March 2021
Estimated Study Completion Date : March 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: Poziotinib - EGFR exon 20 mutant NSCLC

Participant takes 2 Poziotinib tablets by mouth 1 time every day.

Each study cycle is 28 days.

Participant may continue taking the study drug for as long as the doctor thinks it is in their best interest.

Drug: Poziotinib
Poziotinib given at a dose of 16 mg by mouth daily (two tablets of 8mg).

Experimental: Poziotinib - HER2 exon 20 mutant NSCLC

Participant takes 2 Poziotinib tablets by mouth 1 time every day.

Each study cycle is 28 days.

Participant may continue taking the study drug for as long as the doctor thinks it is in their best interest.

Drug: Poziotinib
Poziotinib given at a dose of 16 mg by mouth daily (two tablets of 8mg).




Primary Outcome Measures :
  1. 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.


  2. Adverse Events of Poziotinib in Non-Small Cell Lung Cancer (NSCLC) Participants with EGFR Exon 20 Mutations or HER2 Exon 20 Mutations [ Time Frame: 1 month ]
    Adverse events assessed by Common Terminology Criteria for Adverse Events version 4.03.

  3. Objective Response Rate (ORR) to Poziotinib in Non-Small Cell Lung Cancer (NSCLC) Participants with HER2 (ErBB2) 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.



Secondary Outcome Measures :
  1. 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.


  2. Disease Control Rate of Poziotinib in Non-Small Cell Lung Cancer (NSCLC) Participants with HER2 exon 20 mutant NSCLC [ 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.




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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically or cytologically confirmed recurrent non-small cell lung cancer not amenable to curative intent therapy or stage IV NSCLC
  2. Cohort 1 specific inclusion criteria: Documented EGFR exon 20 mutation 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. Eligible mutations include A763_Y764insFQEA, D770_N771insSVD, D770_N771insNPG, V769_D770insASV, H773_V774insNPH, or any other exon 20 in-frame insertion or point mutation excluding T790M.
  3. Patients must be previously treated with one or more regimens of systemic therapy for locally advanced or metastatic disease. Previously untreated patients are eligible only if EGFR Exon 20 mutation is confirmed using an FDA approved device: cobas® EGFR Mutation Test v2 or therascreen® EGFR RGQ PCR Kit prior to study enrollment.
  4. Cohort 2 specific inclusion criteria: Documented HER2 exon 20 mutation by a CLIA certified laboratory. 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.
  5. Measurable disease by RECIST 1.1.
  6. Age >/= 18 years.
  7. ECOG performance status 0 or 1.
  8. Ability to take pills by mouth
  9. Patients must have normal organ and marrow function as defined below: 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); AST(SGOT)/ALT(SGPT)/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 (creatinine clearance = ([140-age] x body mass/(plasma creatinine x 72) x gender correction factor) or by 24-hours urine collection
  10. Brain metastases are allowed, as long as they are stable and do not require treatment with anticonvulsants or escalating doses of steroids.
  11. 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 (eg combined oral contraceptive pill), barrier protection (eg condom plus spermicide, cervical/vault or intrauterine device), and abstinence. Females of childbearing potential are defined as those who are not surgically sterile (ie, 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. Inclusion Criterion cont'd in # 12.
  12. Continuation from inclusion criterion # 11: 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.
  13. 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 (eg combined oral contraceptive pill), barrier protection (eg condom plus spermicide, cervical/vault cap or intrauterine device), and abstinence.
  14. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  1. EGFR T790M mutation or any other acquired EGFR exon 20 mutation. Patients with coexisting primary EGFR exon 20 and T790M mutations are eligible.
  2. 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.
  3. Any concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment.
  4. 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.
  5. Known hypersensitivity to poziotinib or history of allergic reactions attributed to compounds of similar chemical or biologic composition to poziotinib.
  6. 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
  7. Have any unresolved chronic toxicity with CTCAE version 4.03 Grade >/= 2, from previous anticancer therapy, except for alopecia.
  8. Patient is unable to take drugs orally due to disorders or diseases that may affect gastrointestinal function, such as inflammatory bowel diseases (eg, Crohn's disease, ulcerative colitis) or malabsorption syndrome, or procedures that may affect gastrointestinal function, such as gastrectomy, enterectomy, or colectomy.
  9. 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
  10. Pregnant or breastfeeding women
  11. 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
  12. Recent major surgery within 4 weeks prior to starting study treatment, with the exception of surgical placement for vascular access
  13. Male or female patients of reproductive potential who are not employing an effective method of birth control. Adequate contraception methods include: birth control pills (eg combined oral contraceptive pill), barrier protection (eg condom plus spermicide cervical/vault cap or intrauterine device), and abstinence.
  14. Uncontrolled intercurrent illness including, but not limited to, uncompensated respiratory, cardiac, hepatic, or renal disease, active infection (including hepatitis B, hepatitis C, 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.
  15. Active bleeding disorders.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03066206


Contacts
Contact: John Heymach, MD, PHD 713-792-6363 jheymach@mdanderson.org

Locations
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact       jheymach@mdanderson.org   
Sponsors and Collaborators
M.D. Anderson Cancer Center
Lung Cancer Research Foundation
Spectrum Pharmaceuticals, Inc
Investigators
Principal Investigator: John Heymach, MD, PHD M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03066206     History of Changes
Other Study ID Numbers: 2016-0783
FP00000804 ( Other Grant/Funding Number: Lung Cancer Research Foundation )
NCI-2017-00831 ( Registry Identifier: NCI-CTRP )
First Posted: February 28, 2017    Key Record Dates
Last Update Posted: July 17, 2018
Last Verified: July 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by M.D. Anderson Cancer Center:
Malignant Neoplasm of Respiratory and Intrathoracic Organ
Non-Small Cell Lung Cancer
NSCLC
Advanced
EGFR exon 20 mutation
EGFR-positive
Poziotinib

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms