Clinical trial NCT03480230: Neoadjuvant Compound 121564 Plus Platinum Doublet Chemotherapy in Non-Small Cell Lung Cancer
Official title: Phase II Trial of Neoadjuvant Compound 121564 Plus Platinum Doublet Chemotherapy in Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Non-Small Cell Lung Cancer Stage
Keywords: Non-small cell lung cancer
Platinum doublet chemotherapy
Neoadjuvant
Lead sponsor: American University of Beirut Medical Center
Sponsor class: OTHER
Collaborators: name: Merck KGaA, Darmstadt, Germany
name: Phoenix Clinical Research
First posted: 2018-03-29
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: Open-label, single-arm multi-center phase II trial of neoadjuvant Compound 121564 plus platinum doublet chemotherapy conducted among patients with early stage (IB, II, IIIA) non-small cell lung cancer.

Eligibility criteria: Inclusion Criteria:

1. Males and females aged ≥ 18 years.
2. Histologically confirmed NSCLC (squamous and non-squamous).
3. High-risk stage IB (tumor ≥ 4 cm in size, or grade 3, or with visceral pleura involvement), II or IIIA disease.
4. Have biopsy tissue available (fresh and archived) for PD-L1 and correlative studies testing prior to therapy.
5. Have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤

1. 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:

1. Absolute neutrophil count (ANC) ≥1,500/mcL.
2. Platelets ≥100,000/mcL.
3. Hemoglobin ≥9 g/dL.
4. 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.
5. Serum total bilirubin ≤ ULN.
6. AST (SGOT) and ALT (SGPT) ≤ 1.5 X ULN.
7. Alkaline phosphatase ≤ 2.5 X ULN.
8. International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN unless the subject is receiving anticoagulant therapy.
9. Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless the subject is receiving anticoagulant therapy.

Exclusion Criteria:

1. Subject deemed unfit for surgery (by pulmonary or cardiac assessment).
2. Subject with known autoimmune disease that has required systemic therapy in the last 2 years.
3. Prior organ transplantation including allogenic stem-cell transplantation.
4. 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.
5. 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.
6. Subject on immunosuppressive therapy or corticosteroids within 14 days prior to starting study drugs.
7. Subject with interstitial lung disease that is symptomatic or history of pneumonitis that required oral or systemic glucocorticoids to manage.
8. Subject must have recovered from the effects of major surgery or significant trauma at least 14 days prior to therapy.
9. Subject with previous malignancies are excluded unless complete remission was achieved at least 2 years prior to therapy.
10. Other active malignancy requiring concurrent intervention.
11. Subject with active infection requiring systemic therapy.
12. Subject with known history of testing positive for human immunodeficiency virus (HIV) or known to have acquired immunodeficiency syndrome (AIDS).
13. Subject has known active hepatitis B or C.
14. Vaccination within 4 weeks of the first dose of Compound 121564 and while on trials is prohibited except for administration of inactivated vaccines.
15. Subject is pregnant or breastfeeding.
16. Subject has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
17. Subject previously had a severe hypersensitivity reaction to any of the study drugs.
18. Subject is currently participating and receiving study therapy from another clinical trial.
19. Subject had prior treatment with any other anti-PD-1, or PD-L1 or PD-L2 agent or an antibody targeting other immuno-regulatory receptors or mechanisms.
20. Patient who is not willing to sign the consent form.
21. Legal incapacity or limited legal capacity patients receiving other oncology specific medication not authorized in the protocol.

Primary outcomes:
measure: Overall Response Rate (ORR) as assessed by RECIST 1.1 criteria
timeFrame: At week 9
Secondary outcomes:
measure: Pathologic complete response rate
timeFrame: At 12 weeks
measure: Major pathologic response rate (<10% viable tumor cells)
timeFrame: At 12 weeks
measure: Progression-Free Survival (PFS)
timeFrame: At 1, 2 and 3 years
measure: Overall Survival (OS)
timeFrame: At 1, 2 and 3 years
measure: Overall Response Rate (ORR) as assessed by RECIST 1.1 criteria in enrolled squamous vs. non-squamous lung cancer patients
timeFrame: At week 9
measure: Progression-Free Survival (PFS) in enrolled squamous vs. non-squamous lung cancer patients
timeFrame: At 1, 2 and 3 years
measure: Overall Survival (OS) in enrolled squamous vs. non-squamous lung cancer patients
timeFrame: At 1, 2 and 3 years
measure: Patient-related outcomes Quality of Life assessment using the questionnaire for functional assessment of cancer therapy for patients with lung cancer (FACT-L version 4)
timeFrame: At week 9
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v 4.0
timeFrame: With every administration
measure: Overall Response Rate (ORR) as assessed by RECIST 1.1 criteria in patients with 50% or more PD-L1 vs. patients with less than 50% PD-L1
timeFrame: At week 9
measure: Progression-Free Survival (PFS) in patients with 50% or more PD-L1 vs. patients with less than 50% PD-L1
timeFrame: At 1, 2 and 3 years
measure: Overall Survival (OS) in patients with 50% or more PD-L1 vs. patients with less than 50% PD-L1
timeFrame: At 1, 2 and 3 years
Other outcomes:
Locations:
city: Amman
country: Jordan
facility: King Hussein Cancer Center
city: Beirut
country: Lebanon
facility: American University of Beirut Medical Center
city: Beirut
country: Lebanon
facility: Bellevue Medical Center
city: Beirut
country: Lebanon
facility: Lebanese American University Medical Center-Rizk Hospital
city: Sidon
country: Lebanon
facility: Hammoud Hospital University Medical Center
Study officials:
affiliation: American University of Beirut Medical Center
name: Arafat H Tfayli, MD
role: PRINCIPAL_INVESTIGATOR
References: