Necitumumab in the Neoadjuvant Setting With Gemcitabine in Surgically Resectable - 14X-US-I001
Condition: Squamous Cell Lung Cancer
MeSH terms: Lung Neoplasms
Intervention: Necitumumab-Gemcitabine-Cisplatin; Evaluation to determine if patient is a candidate to proceeed with surgical resection or not
Intervention description: Gemcitabine 1250mg/m2 IV on D1, D8
Cisplatin 75mg / m2 IV on D1
Necitumumab 800mg IV on D1, D8 (peripheral blood for effector cells and cytokine measurements prior to each cycle) Repeat cycle every 21 days up to 3 cycles.; Patients will be evaluated with repeat imaging studies (PET/CT or CT Chest, Abdomen, Pelvis) and will be re-evaluated for surgical resection. Patients who had progressive disease or are NOT a surgical candidate will come off the study and will be treated according to standard therapies. All patients will be followed up for 2-year disease-free survival and overall survival
Intervention MeSH terms: Gemcitabine; Necitumumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: Feasibility and Biomaker Study
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Neoadjuvant Chemotherapy; NSCLC; nacitumumab

Summary:

      This will be a single-arm study to primarily evaluate the feasibility of administering
      necitumumab added to gemcitabine and cisplatin as neoadjuvant treatment in treatment-naïve
      patients with stage IB (tumor size >4cm), II or IIIA squamous NSCLC. Feasibility will be
      assessed by the proportion of patients able to proceed to surgery after administering
      necitumumab in the neoadjuvant setting. These patients would otherwise be offered standard
      adjuvant chemotherapy (without necitumumab) for squamous cell lung cancer. Determination of
      surgical resectability will be reviewed at a multidisciplinary thoracic tumor board, attended
      by surgical oncology, medical oncology, radiation oncology, radiology, and pathology.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed squamous cell non-small
             cell lung cancer with any of the following stage groupings: IB with tumor size >4cm,
             II or potentially resectable IIIA.

          -  Patients who have been evaluated by thoracic surgery and eligible for resection.

          -  Patients must have adequate fresh frozen paraffin embedded (FFPE) tumor tissue
             available to perform pre-treatment biomarker testing.

          -  No prior systemic treatment for squamous cell non-small cell lung cancer.

          -  Age ≥18 years.

          -  ECOG performance status 0-1 (Karnofsky ≥70%, see Appendix A).

          -  Patients must have hematologic function as defined by:

               -  absolute neutrophil count ≥1.5 x 109/L

               -  hemoglobin ≥9.0 g/dL

               -  platelets ≥100 x 109/L

          -  Patients must have organ function as defined below:

               -  bilirubin ≤1.5 × the upper limit of normal (ULN), alkaline phosphatase (ALP),
                  alanine aminotransferase (ALT) and asparate transaminase (AST) ≤3.0 times ULN.
                  For patients with hepatic metastases, ALT and AST equaling ≤5.0 times ULN are
                  acceptable.

               -  If a patient experiences elevated ALT >5 × ULN and elevated total bilirubin >2 ×
                  ULN, clinical and laboratory monitoring should be initiated by the investigator.
                  For patients entering the study with ALT >3 × ULN, monitoring should be triggered
                  at ALT >2 × baseline.

               -  calculated creatinine clearance >50mL/min (per the Cockcroft-Gault formula).

               -  serum albumin ≥2.5 g/dL

          -  Patients may be on a stable regimen of therapeutic anticoagulation or may be receiving
             prophylactic anticoagulation of venous access devices.

          -  The patient is a woman of child-bearing potential who tests negative for pregnancy
             within 14 days prior to receiving first dose of study medication based on serum
             pregnancy test and agrees to use 2 methods of birth control or abstain from
             heterosexual activity during the study and for 6 months following the last dose of the
             study drug(s) or country requirements, whichever is longer or be of non-child bearing
             potential.

          -  Non-childbearing potential is defined as (by other than medical reasons):

               -  ≥45 years of age and has not had menses for greater than 2 years,

               -  amenorrheic for < 2 years without a hysterectomy and oophorectomy and a
                  follicle-stimulating hormone value in the postmenopausal range upon pretrial
                  (screening) evaluation, or

               -  post hysterectomy, oophorectomy or tubal ligation. Documented hysterectomy or
                  oophorectomy must be confirmed with medical records of the actual procedure or
                  confirmed by an ultrasound. Tubal ligation must be confirmed with medical records
                  of the actual procedure otherwise the patient must be willing to use 2 adequate
                  barrier methods throughout the study, starting with the screening visit through 6
                  months after the last dose of study therapy.

          -  Ability to understand and the willingness to sign a written informed consent document.

          -  The patient is willing to comply with protocol schedules and testing. -

          -  Exclusion Criteria: Patients with histologically or cytologically confirmed
             non-squamous cell, small cell or mixed histology lung carcinoma.

          -  Patients with stage IIIB or stage IV disease.

          -  Prior history of other malignancy, provided that he/she has been free of disease for
             ≥3 years, with the exception of in-situ carcinoma of the cervix or completely resected
             basal cell carcinoma of the skin.

          -  Patients who are receiving any other investigational agents.

          -  The patient has a known allergy / history of hypersensitivity reaction to any of the
             treatment components, including any ingredient used in the formulation of necitumumab,
             or any other contraindication to one of the administered treatments.

          -  History or evidence of current clinically relevant coronary artery disease ≥ Grade III
             by the Canadian Cardiovascular Society Angina Grading Scale or uncontrolled congestive
             heart failure of current > Class III as defined by the New York Heart Association.

          -  The patient has experienced myocardial infarction within 6 months prior to study
             enrollment.

          -  The patient has any ongoing or active infection, including active tuberculosis or
             known infection with the human immunodeficiency virus.

          -  Recent (within 30 days before enrollment) or concurrent yellow fever vaccination.

          -  The patient is pregnant or breastfeeding, or expecting to conceive or father children
             within the projected duration of the trial, starting with the screening visit through
             6 months after the last dose of trial treatment.

          -  History of arterial or venous thromboembolism within 3 months prior to study
             enrollment. Patients with a history of venous thromboembolism beyond 3 months prior to
             study enrollment can be enrolled if they are appropriately treated with low molecular
             weight heparin.

          -  The patient has any NCI-CTCAE Version 4.0 Grade ≥2 peripheral neuropathy.

          -  The patient has any other serious uncontrolled medical disorders or psychological
             conditions that would, in the opinion of the investigator, limit the patient's ability
             to complete the study or sign an informed consent document.