TAS-102 in Previously Treated Unresectable or Metastatic Squamous Cell Lung Carcinoma (UF-STO-LUNG-003)
Condition: Squamous Cell Lung Carcinoma
MeSH terms: Carcinoma; Lung Neoplasms
Intervention: TAS-102
Intervention description: Days 1 through 5: TAS-102 (35 mg/m2/dose) orally 2 times daily with the first dose administered in the morning of Day 1 of each cycle and the last dose administered in the evening of Day 5. TAS-102 is to be taken within 1 hour of completion of morning and evening meals.
Days 6 through 7: Rest
Days 8 through 12: TAS-102 (35 mg/m2/dose) orally 2 times daily with the first dose administered in the morning of Day 8 of each cycle and the last dose administered in the evening of Day 12.
Days 13 through 28: Rest
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 4.0
Sex: All
Minimum age: 18 Years
Maximum age: 90 Years
Healthy volunteers: No
Keywords: lung; metastatic; carcinoma

Summary:

      This is a non-randomized, open label, sequentially enrolling phase II study with a Simon
      two-step enrollment design to evaluate the activity of TAS-102 in previously treated
      unresectable or metastatic squamous non-small cell cancer after progression through or
      intolerance to prior systemic therapy. The trial therapy of TAS-102 is to be administered
      orally at 35 mg/m2 each dose twice daily. The primary objective of the trial is to determine
      the progression-free survival, in months, of subjects receiving TAS 102 for the treatment of
      unresectable or metastatic recurrent squamous non-small cell lung cancers.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Those who will be eligible will be all patients with unresectable and/or metastatic
             squamous cell non-small cell lung cancer who have disease which has been previously
             treated with an Food & Drug Administration (FDA)- or National Comprehensive Cancer
             Network (NCCN)-approved platinum doublet. Patients who have not received such therapy
             must have medical reasons for not receiving such therapy. Those who have a molecularly
             targetable genetic mutation in their tumor must have also received the appropriate
             specific therapy for that mutation. All will be appropriate candidates for
             chemotherapy treatment.

        Subjects must meet all of the additional following criteria to be eligible for study
        participation:

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status <2

          -  Life expectancy > 12 weeks

          -  Male or female' age >18 years

          -  Patients of childbearing potential must be using an effective means of contraception.

          -  Histologic diagnosis of squamous non-small cell lung cancer that has been treated
             adequately in the metastatic or unresectable setting with a platinum doublet
             chemotherapy regimen and now has evidence of disease progression. Patients may have
             also received additional chemotherapy, such as an immune checkpoint inhibitor or no
             more than one additional cytotoxic agent (thus participants may have received between
             one to three prior lines of therapy for metastatic or unresectable disease).

          -  Patients who have received platinum-based doublet therapy in the neoadjuvant or
             adjuvant setting will only be eligible if they have experienced disease progression
             after their last dose of cytotoxic chemotherapy.

          -  Patients who have a neoplasm for which there currently exists an FDA-approved targeted
             therapy (such as to epidermal growth factor receptor [EGFR] activating mutations, or
             ALK or ROS1 gene rearrangements) must have received all such targeted therapies and
             either exhibited progressive disease through such treatments, or have been shown to be
             intolerant of such therapies, prior to enrollment on this study.

          -  Baseline laboratory values (bone marrow, renal, hepatic):

          -  Adequate bone marrow function:

          -  Absolute neutrophil count >1000/µL

          -  Platelet count >100'000/µL

          -  Renal function:

          -  Serum creatinine < 2.0 mg/dL

          -  Hepatic function:

          -  Bilirubin <1.5x upper limit of normal (ULN)

          -  Serum calcium < 12 mg/dL

          -  Women of childbearing potential (WOCBP) must be using an adequate method of
             contraception to avoid pregnancy throughout the study and for at least 6 months after
             the last dose of study drug to minimize the risk of pregnancy. Prior to study
             enrollment, women of childbearing potential must be advised of the importance of
             avoiding pregnancy during trial participation and the potential risk factors for an
             unintentional pregnancy. WOCBP include any woman who has experienced menarche and who
             has not undergone successful surgical sterilization (hysterectomy, bilateral tubal
             ligation, or bilateral oophorectomy) or who is not post-menopausal. Post-menopause is
             defined as:

          -  Amenorrhea that has lasted for ≥ 12 consecutive months without another cause, or

          -  For women with irregular menstrual periods who are taking hormone replacement therapy
             (HRT), a documented serum follicle-stimulating hormone (FSH) level of greater than 35
             mIU/mL.

          -  Males with female partners of child-bearing potential must agree to use
             physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy)
             throughout the study and should avoid conceiving children for 3 months following the
             last dose of study drug.

          -  Subjects must have provided written informed consent and be willing to comply with all
             study-related procedures.

        Exclusion Criteria:

          -  Pregnant or lactating females

          -  Patients with a mixed histology NSCLC, such as adenosquamous carcinoma, where the
             squamous component is <50% of the assessed lesion

          -  Patients with a mixed histology where there are any small cell elements

          -  Patients who have not received and progressed through, refused, or been intolerant of,
             a commonly utilized platinum-doublet therapy (cisplatin or carboplatin paired with
             docetaxel, paclitaxel, nab-paclitaxel, gemcitabine, vinorelbine, etoposide or
             irinotecan) administered for the treatment of unresectable or metastatic lung cancer.

          -  Patients who have not received the appropriate prior targeted therapy for their lung
             cancer if eligible

          -  Any invasive malignancy treated within 3 years prior to Cycle 1, Day 1

          -  Myocardial infarction or ischemia within the 6 months before Cycle 1' Day 1

          -  Uncontrolled' clinically significant dysrhythmia, or prolonged QT segment

          -  Uncontrolled malignant disease in the central nervous system (previously treated
             disease is eligible, provided it has been radiographically stable for at least four
             weeks)

          -  Radiotherapy within the 2 weeks before Cycle 1, Day 1. If any radiation has been
             administered to the target lesion there must be evidence of growth by radiographic
             assessments or physical examination

          -  Major surgery within the 2 weeks before Cycle 1, Day 1

          -  Any co morbid condition that' in the view of the attending physician' renders the
             patient at high risk from treatment complications

          -  Subjects unwilling to use an acceptable method to avoid pregnancy for the entire study
             period and for at least 24 weeks after the last dose of study drug.

          -  History of any other disease, metabolic dysfunction, physical examination finding, or
             clinical laboratory finding giving reasonable suspicion of a disease or condition that
             contraindicates the use of protocol therapy or that might affect the interpretation of
             the results of the study or that puts the subject at high risk for treatment
             complications, in the opinion of the treating physician.

          -  Prisoners or subjects who are involuntarily incarcerated.

          -  Subjects who are compulsorily detained for treatment of either a psychiatric or
             physical illness.

          -  Subjects demonstrating an inability to comply with the study and/or follow-up
             procedures.