Cisplatin and Nab-paclitaxel for (N2) Defined NSCLC

Phase 2

Terminated

Conditions: Stage IIIA Non-Small Cell Lung Cancer

Interventions: Drug: Neoadjuvant Cisplatin, nab-paclitaxel
Drug: Adjuvant Cisplatin,nab-paclitaxel
Drug: Adjuvant cisplatin+pemetrexed or cisplatin+gemcitabine

Registration Number: NCT02276560

Lead Sponsor: UNC Lineberger Comprehensive Cancer Center

Brief Summary: The purpose of this research study is to determine whether giving cisplatin and nab-paclitaxel before surgery will reduce the presence of disease in certain areas of the lung at the time of surgery.

Detailed Description: Objectives

To estimate the rate of N2 nodal clearance at time of surgery in patients with NSCLC undergoing treatment with neoadjuvant nab-paclitaxel plus cisplatin and surgery.

Estimate response rate and complete response rate in non-small cell lung cancer (NSCLC) after 3 cycles of neoadjuvant nab-paclitaxel plus cisplatin

Estimate complete pathological response of primary tumor and lymph nodes at the time of surgery in patients with NSCLC undergoing treatment with neoadjuvant nab-paclitaxel plus cisplatin

Estimate disease free survival for all patients who undergo surgery and also stratified by nodal clearance

Patients will be assigned to receive three (3) cycles of cisplatin (mg/m2) and nab-paclitaxel (125 mg/m2). Surgery will then be conducted per standard of care.

Approximately 4-12 weeks after the surgical resection, patients will receive one of three available treatment regimens based on the results of the surgical reports, which include: Two four week cycles of therapy of Cisplatin and Nab-paclitaxel; Four three-week cycles of Cisplatin and Pemetrexed, or four three-week cycles of Cisplatin and Gemcitabine

Thirty (30) days after treatment ends, subjects will be followed for any ongoing serious adverse events, if necessary, and every 3-6 months thereafter for two years.

After the two years of follow-up, subjects will be followed for survival and disease status

Estimate overall survival for entire group and stratified by nodal clearance

To estimate event free survival (EFS)

Estimate time to distant recurrence and time to local recurrence following total study procedures

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 1

Inclusion Criteria

18 years of age; no upper age limit
Diagnosis of NSCLC, histologically or cytologically confirmed
Pathologic mediastinal staging to include endobronchial ultrasound with or without endoscopic ultrasound (EBUS =/- EUS) including evaluation of N3 nodes
Systemic staging including CT that covers the chest, liver and adrenal glands or a PET/CT; MRI of the brain is required and must be negative for metastatic spread. If a patient is unable to tolerate MRI or has a contraindication to MRI, a head CT scan with and without contrast is acceptable
International Association for the Study of Lung Cancer (IASLC) version 7, subset of stage IIIA single station (N2) disease; specifically T1a-T3, N2(+) with no invasion of key structures (e.g., chest wall or diaphragm)
Surgically resectable disease, and patient deemed an appropriate surgical candidate by a thoracic surgeon prior to enrollment
Eastern Cooperative Oncology Group (ECOG) performance status 0-1
Adequate organ and bone marrow function as defined by:

Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3; Hemoglobin ≥ 10g/dL (it is acceptable to reach this through transfusion); Platelets > 100,000 cells/mm3; Creatinine clearance ≥ 60 mg/dL (Cockcroft-Gault equation); Total bilirubin ≤ 1.5 mg/dL; Alkaline phosphatase ≤ 2.5 x upper limit of normal (ULN); Alanine aminotransferase (ALT, SGPT) ≤ 2.5 x ULN; Aspartate aminotransferase (AST, SGOT) ≤ 2.5 x ULN;

Women of childbearing potential and sexually active men must agree to use effective contraception prior to study entry, for the duration of study participation and for three months after completing treatment. Adequate contraception is defined as any medically recommended method (or combination of methods) per standard of care
Negative serum or urine Human Chorionic Gonadotropin(b-hCG) pregnancy test within 14 days of D1 of neoadjuvant chemotherapy for women of childbearing potential
Informed consent obtained and signed

Exclusion Criteria

Forced expiratory volume (FEV) ≤ 1.2 L/s
T3 tumor defined by invasion of key structures (only T3 defined by size > 7cm allowed)
Any lymph code > 3 cm or multistation N2 lymphadenopathy
Patient better served by concurrent chemoradiotherapy: The protocol recognizes that institutional standards regarding which patients are best served by operative and nonoperative approaches vary. Therefore, consistent with the American College of Chest Physicians (ACCP) guidelines, the protocol recommends multidisciplinary discussion of each patient and enrollment only of patients felt best serviced by the approach described herein
≥ Grade 2 pre-existing peripheral neuropathy (per CTCAEv4)
Prior history of hypersensitivity to taxane or platinum therapy. If either agent was previously administered, the patient must have tolerated it well and have recovered from any adverse events
Recurrent disease or second primary lung cancer (only de novo IIIA disease allowed)
Other active, invasive malignancy requiring ongoing therapy or expected to require systemic therapy within two years; localized squamous cell carcinoma of the skin, basal-cell carcinoma of the skin, carcinoma in-situ of the cervix, or other malignancies requiring locally ablative therapy only will not result in exclusion.
Prior treatment of any kind for this malignancy
Have received treatment with any drug that has not received regulatory approval for that indication within the 30 days prior to study entry
Any serious, uncontrolled medical disorder that would impair the ability of the subject to receive protocol driven therapy

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Neoadjuvant Cisplatin,nab-paclitaxel	Neoadjuvant Cisplatin, nab-paclitaxel	Neoadjuvant cisplatin (75 mg/m2) D1 and nab-paclitaxel (125 mg/m2) D1, 8, 15, repeat each 28D cycle x 3 and then surgery per standard of care
Adjuvant Cisplatin,nab-paclitaxel	Adjuvant Cisplatin,nab-paclitaxel	Adjuvant cisplatin (75mg/m2) D1, nab-paclitaxel (125 mg/m2)for D1, 8, 15 repeat each 28D x 2
Cisplatin+pemetrexed or gemcitabine	Adjuvant cisplatin+pemetrexed or cisplatin+gemcitabine	Adjuvant cisplatin (75mg/m2) D1, pemetrexed (500mgm2) D1 or; cisplatin (75 mg/m2),Gemcitabine (1000mg/m2) D1, 8 repeat each 21D cycle x 4

Primary Outcome Measures

Name	Time	Method
Rate of N2 Nodal Clearance	3 Months	N2 disease is defined as involvement of the ipsilateral mediastinal and/or subcarinal lymph nodes; if disease is cleared form these locations, then there is N2 nodal clearance

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (9): Rex Cancer Center and Rex of Wakefield
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Raleigh, North Carolina, United States
Swedish Cancer Institute
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Seattle, Washington, United States
Emory - Winship Cancer Institute
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Atlanta, Georgia, United States
Moffitt Cancer Center
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Tampa, Florida, United States
University of Kansas Cancer Center
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Kansas City, Kansas, United States
Ochsner Cancer Institute
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New Orleans, Louisiana, United States
Case Western Reserve University - Seidman Cancer Center
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Cleveland, Ohio, United States
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
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Chapel Hill, North Carolina, United States
University of Pittsburgh Medical Center
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Pittsburgh, Pennsylvania, United States