Neoadjuvant Compound 121564 Plus Platinum Doublet Chemotherapy in Non-Small Cell Lung Cancer

NCT03480230 | Unknown Phase 2 DMC

• 2 other identifiers: BIO-2017-0467MS100070_0020
• Study Type: interventional
• Target: 60
• Locations: 2 countries
• Sites: 5

Brief Summary

The purpose of this study is to assess the response rate to neoadjuvant Compound 121564 plus platinum doublet chemotherapy in patients with early stage non-small cell lung cancer.

Conditions

Non-Small Cell Lung Cancer Stage

Keywords

Non-small cell lung cancer; Platinum doublet chemotherapy; Neoadjuvant

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR) as assessed by RECIST 1.1 criteria

  To assess the overall response rate (ORR) of patients receiving neoadjuvant Compound 121564 plus platinum doublet chemotherapy based on RECIST 1.1 criteria

  At week 9

Secondary Outcomes (12)

• Pathologic complete response rate

  At 12 weeks

• Major pathologic response rate (<10% viable tumor cells)

  At 12 weeks

• Progression-Free Survival (PFS)

  At 1, 2 and 3 years

• Overall Survival (OS)

  At 1, 2 and 3 years

• Overall Response Rate (ORR) as assessed by RECIST 1.1 criteria in enrolled squamous vs. non-squamous lung cancer patients

  At week 9

Study Arms (1)

Treatment arm

EXPERIMENTAL

1. Non-squamous histology: * Compound 121564 10 mg/Kg administered over 60 minutes given intravenously every 2 weeks for 4 doses. * Compound 565994 500 mg/m2 administered over 10 minutes, and * Compound 232673 AUC=5 mg/mL/min administered over 15-60 minutes or Compound 454893 at 75 mg/m2 over 1 hour. * Compound 565994 and platinum are to be given on day 1 of every 3-week cycle for 3 cycles. 2. Squamous histology: * Compound 121564 10 mg/Kg administered over 60 minutes every 2 weeks for 4 doses. * Compound 232673 AUC=5 mg/mL/min administered over 15-60 minutes or Compound 454893 at 75 mg/m2 over 1 hour on day 1 of every cycle. * Compound 343782 1,000 mg/m2 administered over 30 minutes on days 1 and 8 of each cycle. * Platinum and Compound 343782 will be given for 3 cycles.

Drug: Compound 121564

Interventions

Compound 121564 DRUG

Compound 121564 10 mg/Kg administered over 60 minutes given intravenously every 2 weeks for 4 doses plus chemotherapy depending on tumor histology.

Treatment arm

Eligibility Criteria

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

You may qualify if:

• Males and females aged ≥ 18 years.
• Histologically confirmed NSCLC (squamous and non-squamous).
• High-risk stage IB (tumor ≥ 4 cm in size, or grade 3, or with visceral pleura involvement), II or IIIA disease.
• Have biopsy tissue available (fresh and archived) for PD-L1 and correlative studies testing prior to therapy.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤
• \. 6) Have a life expectancy of ≥ 6 months. 7) No previous systemic anticancer therapy or surgical resection for his or her NSCLC. 8) Subject has voluntarily agreed to participate by giving written informed consent for the trial. 9) Subject must be willing and able to comply with scheduled visits, treatment schedule and laboratory testing. 10) Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 24 hours prior to receiving the first dose of study medication. 11) Females should not be breastfeeding. 12) Female subjects of childbearing potential as well as males sexually active with women of childbearing potential must be willing to use an adequate method of contraception. 13) Have pulmonary and cardiac function testing deemed adequate for thoracic surgical intervention. 14) Have adequate organ function by meeting the following:
• Absolute neutrophil count (ANC) ≥1,500/mcL.
• Platelets ≥100,000/mcL.
• Hemoglobin ≥9 g/dL.
• Serum creatinine ≤1.5 X upper limit of normal (ULN) OR calculated creatinine clearance (CrCl) (GFR can also be used in place of creatinine or CrCl) ≥60 mL/min for subjects with creatinine levels \> 1.5 X institutional ULN.
• Serum total bilirubin ≤ ULN.
• AST (SGOT) and ALT (SGPT) ≤ 1.5 X ULN.
• Alkaline phosphatase ≤ 2.5 X ULN.
• International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN unless the subject is receiving anticoagulant therapy.
• Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless the subject is receiving anticoagulant therapy.

You may not qualify if:

• Subject deemed unfit for surgery (by pulmonary or cardiac assessment).
• Subject with known autoimmune disease that has required systemic therapy in the last 2 years.
• Prior organ transplantation including allogenic stem-cell transplantation.
• Clinically significant (i.e. active) cardiovascular disease: cerebral vascular accident/stroke (\< 6 months prior to enrollment), myocardial infarction (\< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
• Persisting toxicity related to prior therapy (NCI CTCAE v. 4.03 Grade \> 1); however, alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on investigator's judgment are acceptable.
• Subject on immunosuppressive therapy or corticosteroids within 14 days prior to starting study drugs.
• Subject with interstitial lung disease that is symptomatic or history of pneumonitis that required oral or systemic glucocorticoids to manage.
• Subject must have recovered from the effects of major surgery or significant trauma at least 14 days prior to therapy.
• Subject with previous malignancies are excluded unless complete remission was achieved at least 2 years prior to therapy.
• Other active malignancy requiring concurrent intervention.
• Subject with active infection requiring systemic therapy.
• Subject with known history of testing positive for human immunodeficiency virus (HIV) or known to have acquired immunodeficiency syndrome (AIDS).
• Subject has known active hepatitis B or C.
• Vaccination within 4 weeks of the first dose of Compound 121564 and while on trials is prohibited except for administration of inactivated vaccines.
• Subject is pregnant or breastfeeding.

Sponsors & Collaborators

• Arafat Tfayli: lead
• Merck KGaA, Darmstadt, Germany: collaborator
• Phoenix Clinical Research: collaborator

Study Sites (5)

King Hussein Cancer Center

Amman, Jordan

NOT YET RECRUITING

American University of Beirut Medical Center

Beirut, Lebanon

RECRUITING

Bellevue Medical Center

Beirut, Lebanon

NOT YET RECRUITING

Lebanese American University Medical Center-Rizk Hospital

Beirut, Lebanon

RECRUITING

Hammoud Hospital University Medical Center

Sidon, Lebanon

NOT YET RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

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

Study Officials

• Arafat H Tfayli, MD

  American University of Beirut Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Arafat H Tfayli, MD

CONTACT

+961 1 350 000; at35@aub.edu.lb

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Clinical Medicine

Study Record Dates

• First Submitted: March 14, 2018
• First Posted: March 29, 2018
• Study Start: June 26, 2018
• Primary Completion: November 1, 2022
• Study Completion: November 1, 2022
• Last Updated: August 14, 2018

Record last verified: 2018-08

Locations

LE (4); JO (1)