Clinical Trials /

Necitumumab in the Neoadjuvant Setting With Gemcitabine in Surgically Resectable - 14X-US-I001

NCT03574818

Description:

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.

Related Conditions:
  • Squamous Cell Lung Carcinoma
Recruiting Status:

Terminated

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Necitumumab in the Neoadjuvant Setting With Gemcitabine in Surgically Resectable - 14X-US-I001
  • Official Title: A Feasibility and Biomarker Study to Evaluate Necitumumab in the Neoadjuvant Setting With Gemcitabine and Cisplatin in Surgically Resectable Squamous Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: 2017-8108
  • NCT ID: NCT03574818

Conditions

  • Squamous Cell Lung Cancer

Interventions

DrugSynonymsArms
Necitumumab-Gemcitabine-CisplatinPORTRAZZA™ - GEMZAR™ - PLATINOLArm 1

Purpose

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.

Detailed Description

      The goal of this study is to explore whether it is possible to add a drug called necitumumab
      to standard treatment for patients with squamous cell lung cancer that can be surgically
      removed. This study is important because it will determine whether there is added benefit to
      giving necitumumab with chemotherapy before surgery. It is currently already known that
      chemotherapy given before or after surgery has better outcomes compared to only receiving
      surgery. Results from this study may help to develop more effective treatments for patients
      with squamous cell lung cancer.

      The U.S. Food and Drug Administration (FDA) has approved necitumumab in combination with
      chemotherapy drugs called gemcitabine and cisplatin to treat stage IV or metastatic squamous
      cell lung cancer, but the FDA has not approved necitumumab to treat squamous cell lung cancer
      that can be surgically removed.

      Analyzing the tumor cells from many cases of squamous cell lung cancer has shown that this
      cancer often has a special protein called EGFR. Necitumumab is a drug that targets EGFR.

      Results from a recent medical study showed that patients with stage IV or metastatic squamous
      cell lung cancer who received necitumumab with gemcitabine and cisplatin showed a small, but
      significant, improvement in survival. We believe trying to gather more information about the
      way necitumumab interacts with cancer cells will help to learn how to use necitumumab more
      effectively.

      This study will allow to see the effects of treating an earlier stage of squamous cell lung
      cancer using necitumumab with gemcitabine and cisplatin. It will also allow us to better
      analyze tumor cells after they have been treated with necitumumab and chemotherapy that are
      obtained after surgical resection. Other blood samples that will be drawn during the
      treatment will also allow to see the effect of necitumumab on both the body and the tumor
      cells and to observe any side effects that may result from this treatment.
    

Trial Arms

NameTypeDescriptionInterventions
Arm 1ExperimentalChemotherapy and Necitumumab Regimen Gemcitabine 1250mg/m2 IV over 30 minutes, days 1 and 8 following necitumumab, Cisplatin 75mg/m2 IV over 60 minutes, day 1, immediately following gemcitabine,each cycle is 3 weeks (21 days). Necitumumab 800mg absolute dose IV over a minimum of 60 minutes, days 1 and 8 prior to chemotherapy regimen Each cycle is 3 weeks (21 days). The regimen will be given for a total of 3 cycles. The regimen will be given for a total of 3 cycles.
  • Necitumumab-Gemcitabine-Cisplatin

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Surgically resectable
Time Frame:up to 63 days
Safety Issue:
Description:Patients able to proceed to surgery after administering necitumumab in the neoadjuvant setting with gemcitabine and cisplatin in surgically resectable patients with stage IB with tumor size >4cm, II and potentially resectable IIIA squamous cell lung cancer.

Secondary Outcome Measures

Measure:Response rate
Time Frame:Up to 63 days
Safety Issue:
Description:Response rate of neoadjuvant chemotherapy with Necitumumab, gemcitabine, and cisplatin.
Measure:Toxicity frequency and severity
Time Frame:Up to 63 days
Safety Issue:
Description:Frequency and severity of toxicities in patients while receiving neoadjuvant chemotherapy with necitumumab, gemcitabine and cisplatin.
Measure:Pathologic response
Time Frame:Up to 63 days
Safety Issue:
Description:Pathologic complete response (pCR) rate in patients receiving neoadjuvant chemotherapy with necitumumab, gemcitabine, and cisplatin followed by surgical resection.
Measure:DFS
Time Frame:two years
Safety Issue:
Description:2-year disease-free survival (DFS) in patients receiving neoadjuvant chemotherapy with necitumumab, gemcitabine, and cisplatin followed by surgical resection.
Measure:OS
Time Frame:two years
Safety Issue:
Description:Overall survival at 2 years in patients receiving neoadjuvant chemotherapy with necitumumab, gemcitabine, and cisplatin followed by surgical resection.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Montefiore Medical Center

Trial Keywords

  • Neoadjuvant Chemotherapy; NSCLC; nacitumumab

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