Neoadjuvant Chemoradiation Plus Pembrolizumab Followed By Consolidation Pembrolizumab in NSCLC

NCT02987998 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: CASE4516
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the feasibility and evaluate the safety of delivering chemoradiotherapy, the usual approach to non-small cell lung cancer, in combination with pembrolizumab (MK-3745), followed by consolidation pembrolizumab after surgical resection. Consolidation therapy is treatment given following the initial treatment. Pembrolizumab is an investigational drug (also known as Keytruda), which has been approved by the FDA for use in certain types of skin cancer (melanoma), and for use in certain types of head and neck cancer. However, it has not been approved for use in other cancers such as non-small cell lung cancer (NSCLC). Pembrolizumab is a monoclonal antibody that binds to the surface of some cells of the immune system and activates them against cancer cells. It is not chemotherapy.

Conditions

Stage IIIA Non-Small Cell Lung Cancer

Keywords

Pembrolizumab; Chemoradiation

Outcome Measures

Primary Outcomes (1)

• Number of patients with grade 3 pulmonary toxicity or grade 4 other non hematologic toxicity

  If 5 or fewer (\<25%) of the 20 patients have \> grade 3 pulmonary toxicity or \> grade 4 other nonhematologic toxicity, then this regimen will be deemed safe and feasible for further study

  Up to 5 years

Secondary Outcomes (5)

• Progression Free Survival

  Up to 5 years

• Objective Response Rate

  Up to 5 years

• Complete Pathologic Response Rate

  Up to 5 years

• Nodal Downstaging at Surgery

  Up to 4 weeks after induction treatment

• Overall Survival

  Up to 5 years

Study Arms (1)

Resectable Patients

EXPERIMENTAL

Chemoradiation (Cisplatin + Etoposide + Pembrolizumab with concurrent radiation). Patients will be assessed for surgery followed by consolidation therapy

Drug: Cisplatin; Drug: Etoposide; Drug: Pembrolizumab; Drug: Radiation

Interventions

Cisplatin DRUG

Cisplatin (50mg/m2 IV D1, 8, 29, 36)

Resectable Patients

Etoposide DRUG

Etoposide (50mg/m2 IV D1-5, 29-33)

Resectable Patients

Pembrolizumab DRUG

Pembrolizumab (200mg IV D1, 21, 42)

Resectable Patients

Radiation DRUG

Radiation (1.8Gy/D to 45Gy in 25 fractions)

Resectable Patients

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed stage 3A Non-Small Cell Lung Cancer
• Be willing and able to provide written informed consent/assent for the trial
• Have measurable or unmeasurable disease based on RECIST 1.1.
• Be willing to provide archival tissue from a tumor lesion or obtain a new biopsy if tissue unavailable.
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology group (ECOG) Performance Scale.
• Demonstrate adequate organ function
• Absolute neutrophil count (ANC) ≥1,500/mcL
• Platelets ≥100,000 / mcL
• Hemoglobin ≥9 g/dL or ≥5.6 mmol/L without transfusion or erythropoiesis dependency
• Serum creatinine or Measured or calculated creatinine clearance ≤1.5 X upper limit of normal (ULN) or ≥60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN
• Serum total bilirubin ≤ 1.5 X ULN, or Direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 ULN
• Aspartate transaminase (AST) (SGOT) and Alanine transaminase (ALT) (SGPT) ≤ 2.5 X ULN or ≤ 5 X ULN for subjects with liver metastases
• Albumin ≥2.5 mg/dL
• International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
• Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required

You may not qualify if:

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
• Has a known history of active Bacillus Tuberculosis (TB)
• Hypersensitivity to pembrolizumab or any of its excipients.
• Has had any prior chemotherapy, targeted small molecule therapy, or radiation therapy for the currently diagnosed cancer.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has known history of, or any evidence of active, non-infectious pneumonitis.
• Has an active infection requiring systemic therapy.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
• Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
• Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C

Sponsors & Collaborators

• Nathan Pennell, MD, PhD: lead

Study Sites (1)

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Cisplatin; Etoposide; pembrolizumab; Radiation

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Physical Phenomena

Study Officials

• Nathan Pennell, MD, PhD

  Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Study principal investigator

Study Record Dates

• First Submitted: December 7, 2016
• First Posted: December 9, 2016
• Study Start: May 19, 2017
• Primary Completion: November 28, 2022
• Study Completion: November 28, 2022
• Last Updated: December 19, 2022

Record last verified: 2022-12

Locations

US (1)