Dynamic PET/CT Evaluated the Response of Neoadjuvant Anti-PD1 Combination With Chemotherapy for Ⅱa-Ⅲb NSCLC

NCT04586465 | Unknown Phase 2 FDA Drug

• 1 other identifier: ZDWY.XWK.003
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

The neoadjuvant Immune Checkpoint Inhibitor (ICI) or ICI combination with chemotherapy for Non-small cell lung cancer (NSCLC) had induced higher major pathologic response (MPR) and complete pathological response (PCR). However, the RECIST underestimated the therapeutic response of neoadjuvant ICI therapy. In this study, dynamic PET/CT compared with RECEST 1.1 for the prediction of therapeutic response of NSCLC treated with neoadjuvant ICI combination with chemotherapy.

Conditions

Non-small Cell Lung Cancer Stage II; Non-small Cell Lung Cancer Stage III; PET/CT

Outcome Measures

Primary Outcomes (4)

• Major pathological response

  10% or less residual viable tumor cells

  up to 12 weeks; analysis of surgical resected tumor samples after neoadjuvant therapy

• Dynamic SUV change

  Dynamic PET-CT SUV change

  up to 12 weeks; analysis change of SUV before and after neoadjuvant therapy

• Objective response rate

  CT image assessment of tumor response according to RECIST 1.1 criteria

  up to 12 weeks; analysis change of before and after neoadjuvant therapy

• uptake rate constant (Ki) changes

  uptake rate constant (Ki) changes before and after neoadjuvant therapy

  up to 12 weeks; before and after neoadjuvant therapy

Secondary Outcomes (3)

• Progression free survival

  up to 3 years

• Treatment related adverse events

  12 weeks

• ctDNA change

  12 weeks

Study Arms (1)

Neoadjuvant ICI combination with chemotherapy for stage Ⅱ-Ⅲ NSCLC

EXPERIMENTAL

Eligible patients with clinical stage Ⅱ-Ⅲ NSCLC will receive dynamic PET-CT before and after 3 cycles neoadjuvant pembrolizumab plus chemotherapy, then patients receive surgical resection. Changes in tumor size were evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. Net uptake rate constant of FDG-Ki value based on dynamic PET will be calculated to evaluate Ki changes before and after treatment. Pathological tumor response were evaluated according to IASLC recommendations. Dynamic PET will be compared with RECIST whether it can better predict the pathological tumor response and disease free survival.

Drug: pembrolizumab, pemetrexed, gemcitabine, cisplatin, carboplatin

Interventions

pembrolizumab, pemetrexed, gemcitabine, cisplatin, carboplatin DRUG

Patients will receive 3 cycles pembrolizumab 200mg, fix dose, 60 minute IV infusion combination with chemotherapy. Chemotherapy regimen: ① Eligible patients with non-squamous cell lung cancer, Pemetrexed 500mg/m2, IV infusion on day 1 and cisplatin 75mg/m2 or carboplatin area under the curve (AUC=5), on day 1 of a 3-week schedule for 3 cycles. ② Eligible patients with squamous cell lung cancer. Patients will receive gemcitabine 1250mg/m2 IV on day 1 and day 8, and cisplatin 75mg/m2 or carboplatin AUC=5 on day 1 of a 3-week schedule for 3 cycles

Also known as: Non

Neoadjuvant ICI combination with chemotherapy for stage Ⅱ-Ⅲ NSCLC

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed NSCLC, performed on a biopsy that occurred within the last 60 days
• Computed tomography (CT) and Dynamic PET-CT within the last 30 days showing radiographic stage Ⅱa to Ⅲb lung cancer (mediastinal staging biopsy is allowed but not required) by the American Joint Committee on Cancer (AJCC) 8th edition
• Potentially surgically resectable by a senior thoracic surgeon
• No driver gene mutation.
• Age≥18 years, and ≤75 years
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by the investigator
• Adequate tissue specimens for correlative biomarker analysis. The patient should be willing to provide tissue from a newly obtained biopsy of a tumor lesion and surgical resected tumor lesion.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Resolution of all acute toxic effects of prior chemotherapy, radiotherapy or surgical procedures to NCI CTCAE version (v)5.0 grade 1
• Be willing and able to provide written informed consent for the trial
• Absolute neutrophil count (ANC) \>= 1500 cells/ microlitre(uL) (within 10 days prior to the start of trial treatment). Platelets \>= 100 000 cells/uL (within 10 days prior to the start of trial treatment). Hemoglobin \>= 9.0 g/dL or \>= 5.6 mmol/L (criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks) (within 10 days prior to the start of trial treatment). Creatinine =\< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance, glomerular filtration rate (GFR) can also be used in place of creatinine or creatinine clearance (CrCl) \>= 30 mL/min for patients with creatinine levels \> 1.5 x institutional ULN (within 10 days prior to the start of trial treatment)
• Total bilirubin =\< 1.5 x ULN OR direct bilirubin =\< ULN for patients with total bilirubin levels \> 1.5 x ULN (within 10 days prior to the start of trial treatment)
• Aspartate aminotransferase (AST) or serum glutamic-oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT) or serum glutamate pyruvate transaminase（SGPT) =\< 2.5 x ULN (=\< 5 x ULN for patients with liver metastases) (within 10 days prior to the start of trial treatment)
• International normalized ratio (INR) OR prothrombin time (PT) =\< 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (within 10 days prior to the start of trial treatment)
• Activated partial thromboplastin time (aPTT)/PTT =\< 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (within 10 days prior to the start of trial treatment)

You may not qualify if:

• Any approved anticancer therapy, including chemotherapy, hormonal therapy, or radiotherapy, within 5 years prior to initiation of study treatment; however, the following are allowed:
• Hormone-replacement therapy or oral contraceptives
• Herbal therapy \> 1 week prior to Cycle 1, Day 1 (herbal therapy intended as anticancer therapy must be discontinued at least 1 week prior to Cycle 1, Day 1)
• Malignancies other than the disease under study within 5 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death and with expected curative outcome or undergoing active surveillance per standard-of-care management (e.g., chronic lymphocytic leukemia Rai Stage 0, prostate cancer with Gleason score ≤ 6, and prostate-specific antigen (PSA) ≤ 10 mg/mL, etc.)
• Patients who are receiving any other investigational agents concurrently.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to pembrolizumab, cisplatin, carboplatin, pemetrexed or gemcitabin.
• Patients with active hepatitis B or C infections or a history of HIV infection.
• Patients with past or resolved hepatitis B infection, defined as having a negative hepatitis B surface antigen (HBsAg) test and a positive for the antibody test to detect antibodies to hepatitis B core antigen (anti-HBc) are eligible.
• Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection including tuberculosis (TB), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease
• Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen may be eligible.
• Severe infections within 4 weeks prior to Cycle 1, Day 1, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
• Signs or symptoms of infection within 2 weeks prior to Cycle 1, Day 1 Received oral or IV antibiotics within 2 weeks prior to Cycle 1, Day 1. Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible
• Major surgical procedure within 28 days prior to Cycle 1, Day 1 or anticipation of need for a major surgical procedure during the course of the study

Sponsors & Collaborators

• Fifth Affiliated Hospital, Sun Yat-Sen University: lead

Study Sites (1)

the fifth affiliated hospital of Sun yat-sen university

Zhuhai, Guangdong, 519000, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

pembrolizumab; Pemetrexed; Gemcitabine; Cisplatin; Carboplatin

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)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals

Central Study Contacts

QingDong Cao, MD

CONTACT

0756-2528825; cqd8866@163.com

Study Design

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

Model Details: Dynamic PET-CT compared with RECIST to predict therapeutic response treated with neoadjuvant ICI combined with chemotherapy for stage Ⅱ-Ⅲ NSCLC.

Study Record Dates

• First Submitted: October 12, 2020
• First Posted: October 14, 2020
• Study Start: October 10, 2020
• Primary Completion: November 30, 2021
• Study Completion: June 30, 2022
• Last Updated: August 24, 2021

Record last verified: 2020-10

Locations

CN (1)