Evaluation of Circulating T Cells and Tumor Infiltrating Lymphocytes (TILs) During / After Pre-Surgery Chemotherapy in Non-Small Cell Lung Cancer (NSCLC)

NCT01820754 | Completed Phase 2 Results DMC

• 1 other identifier: Pro00038093
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate whether the combination of neoadjuvant chemotherapy (chemotherapy before surgery) plus ipilimumab for lung cancer increases the number of patients with detectable circulating T cells with specificities against tumor associated antigens (TAA) from zero percent (0%) of patients prior to therapy to 20% of patients after neoadjuvant chemotherapy plus ipilimumab. This is an open label Phase 2 trial. Patients with clinical stage 1B (\>4 cm), 2, (N0-2) or 3 non-small cell lung cancer (NSCLC) and no prior therapy for the current diagnosis of lung cancer will be eligible for the study. Subjects will receive 3 cycles of neoadjuvant chemotherapy (paclitaxel + cisplatin/carboplatin). Ipilimumab will be administered during Cycles 2 and 3 of standard chemotherapy and for up to 4 cycles alone after surgery. Subjects will undergo standard clinically indicated surgical resection of their lung cancer as deemed appropriate by their surgeon. Standard diagnostic and staging work up will be performed including: pathologic/histologic diagnosis of NSCLC, Positron Emission Tomography (PET)/Computed Tomography (CT) scan, brain imaging, and mediastinoscopy. Three cycles of neoadjuvant chemotherapy will be given. Ipilimumab will be added to neoadjuvant chemotherapy for cycles 2 and 3. Standard surgical evaluation and therapy will be performed following completion of neoadjuvant therapy. Two cycles of single agent ipilimumab will be given after surgery (adjuvantly), followed by 2 cycles of maintenance therapy.

Conditions

Non Small Cell Lung Cancer

Keywords

Non Small Cell Lung Cancer; Lung Cancer; Non Small Cell

Outcome Measures

Primary Outcomes (1)

• Percentage of Subjects With Detectable Circulating T Cells After Treatment

  The primary objective of this trial is to determine the percentage of early stage lung cancer patients with detectable circulating T cells specific against tumor-associated antigen (TAA) after receiving platinum based neoadjuvant chemotherapy plus ipilimumab before surgery. Based on Duke intracellular cytokine staining (ICS) assessments over the past 8 years, "detectable" circulating T cells with specificity against TAA are defined as a CD8, CD4, and double positive (DP) (CD4+CD8+) lymphocyte percentage of ≥ 0.05% with each value also being at least twice that of the background unstimulated control value.

  3 months

Secondary Outcomes (4)

• Feasibility and Tolerability of Neoadjuvant Chemotherapy Plus Ipilimumab and Surgery

  6 months

• Median Disease-Free Survival

  5 years

• Number of Subjects Experiencing a Metastasis by Site of Metastasis

  3 months

• Patterns of Pathologic Response and Response Evaluation Criteria in Solid Tumor (RECIST) Response

  3 months

Study Arms (1)

Ipilimumab

EXPERIMENTAL

Neoadjuvant (Pre-Surgery): Cycles 2 and 3: Ipilimumab 10 mg/kg IV over 90 minutes Adjuvant (Post-Surgery): Ipilimumab 10 mg/kg IV every 3 weeks times 2 doses beginning 4 weeks postoperative ( up to 10 weeks if needed for recovery) Maintenance: Ipilimumab 10 mg/kg/IV every 12 weeks times 2 doses

Drug: Ipilimumab; Drug: Paclitaxel, Cisplatin, Carboplatin

Interventions

Ipilimumab DRUG

Neoadjuvant (Pre-Surgery): Cycles 2 and 3: Ipilimumab 10 mg/kg IV over 90 minutes Adjuvant (Post-Surgery): Ipilimumab 10 mg/kg IV every 3 weeks times 2 doses beginning 4 weeks postoperative ( up to 10 weeks if needed for recovery) Maintenance: Ipilimumab 10 mg/kg/IV every 12 weeks times 2 doses

Also known as: Yervoy

Ipilimumab

Paclitaxel, Cisplatin, Carboplatin DRUG

Neoadjuvant (Pre-Surgery) Cycle 1: Paclitaxel 175 mg/m2 IV over 3 hours , followed by Cisplatin 75 mg/m2 IV over 60 minutes or carboplatin AUC 6 IV over 30-60 minutes on day 1(Every 21 days x 1 cycle) Cycles 2 and 3: Ipilimumab 10 mg/kg IV over 90 minutes, Paclitaxel 175 mg/m2 IV over 3 hours , followed by Cisplatin 75 mg/m2 IV over 60 minutes or carboplatin AUC 6 IV over 30-60 minutes on day 1(Every 21 days x 2 cycles)

Also known as: Taxol, Platinol, Paraplatin

Ipilimumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients are eligible to be in the study if they meet all of the following criteria:
• Histologically or cytologically documented non-small cell lung cancer (NSCLC)
• Clinical stage 1B (≥4cm per CT), Stage 2A/2B, or Stage 3 (N0-2) amenable to surgical resection
• Patients must be deemed a surgical candidate
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• No prior chemotherapy for current diagnosis of lung cancer
• Age is ≥ (greater than or equal to) 18 years
• No active invasive malignancy in the past 2 years other than non-melanoma skin cancer. Cancers that are in-situ are not considered invasive
• Signed written informed consent including Health Insurance Portability and Accountability Act (HIPAA) authorization according to institutional guidelines
• Adequate Organ Function:
• Absolute neutrophil count (ANC) or absolute granulocyte count (AGC) ≥1500 per microliter (uL)
• Platelets ≥ 100,000 per uL
• Total bilirubin ≤(less than or equal to)1.5 milligram per deciliter (mg/dL)
• Creatinine clearance ≥ 45 milliliter per minute (mL / min); (Creatinine \< 2mg / dL to receive cisplatin)
• Serum glutamic-oxaloacetic transaminase / Serum glutamic pyruvic transaminase (SGOT/SGPT) ≤ 2.5x institutional upper limit normal (ULN)

You may not qualify if:

• Patients will be excluded from the study if they meet any of the following criteria:
• Have had treatment within the last 30 days with a drug that has not received regulatory (Food and Drug Administration (FDA)) approval for any indication at the time of study entry
• Concurrent administration of any other anti-tumor therapy
• Inability to comply with protocol or study procedures
• Active infection requiring intravenous (IV) antibiotics, antifungal or antiviral agents, that in the opinion of the investigator would compromise the patient's ability to tolerate therapy
• Major surgery (other than definitive lung cancer surgery) within two weeks of study or other serious concomitant systemic disorders that, in the opinion of the investigator, would compromise the safety of the patient or compromise the patient's ability to complete the study
• Contraindication to corticosteroids
• Unwillingness to stop taking herbal supplements while on study
• Female patients who are pregnant or breast-feeding
• Autoimmune disease. Patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's Disease, are excluded from this study, as are patients with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\], systemic lupus erythematosus, autoimmune vasculitis \[eg, Wegener's Granulomatosis\]); motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre Syndrome and Myasthenia Gravis)
• Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to 1 month before or after any dose of ipilimumab)
• A history of prior treatment with ipilimumab or prior CD137 agonist or cytotoxic T-lymphocyte-associated protein (CTLA 4) inhibitor or agonist
• Prisoners or patients who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness

Sponsors & Collaborators

• Duke University: lead

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Related Publications (1)

• Yang CJ, McSherry F, Mayne NR, Wang X, Berry MF, Tong B, Harpole DH Jr, D'Amico TA, Christensen JD, Ready NE, Klapper JA. Surgical Outcomes After Neoadjuvant Chemotherapy and Ipilimumab for Non-Small Cell Lung Cancer. Ann Thorac Surg. 2018 Mar;105(3):924-929. doi: 10.1016/j.athoracsur.2017.09.030. Epub 2017 Dec 16.

  PMID: 29258674 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

Ipilimumab; Paclitaxel; Cisplatin; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes

Results Point of Contact

• Title: Neal Ready, MD
• Organization: Duke University Medical Center

neal.ready@duke.edu

919 681-6932

Study Officials

• Neal Ready, MD

  Duke University Medical Center / Thoracic Oncology Program

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2013
• First Posted: March 29, 2013
• Study Start: March 1, 2013
• Primary Completion: April 30, 2018
• Study Completion: April 30, 2018
• Last Updated: February 26, 2021
• Results First Posted: May 22, 2018

Record last verified: 2021-02

Locations

US (1)