Nivolumab, Cisplatin, and Pemetrexed Disodium or Gemcitabine Hydrochloride in Treating Patients With Stage I-IIIA Non-small Cell Lung Cancer That Can Be Removed by Surgery
Overview
- Phase
- Phase 2
- Intervention
- Nivolumab
- Conditions
- Non-Squamous Non-Small Cell Lung Carcinoma
- Sponsor
- Sidney Kimmel Cancer Center at Thomas Jefferson University
- Enrollment
- 14
- Locations
- 2
- Primary Endpoint
- Major Pathologic Response (mpCR) Defined as < 10% Viable Tumor
- Status
- Terminated
- Last Updated
- 2 months ago
Overview
Brief Summary
This phase II trial studies how well Nivolumab, Cisplatin, and Pemetrexed Disodium or Gemcitabine Hydrochloride in treating patients with stage I-IIIA non-small cell lung cancer that can be removed by surgery. Monoclonal antibodies, such as Nivolumab, may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as Cisplatin and Pemetrexed Disodium or Gemcitabine Hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving Nivolumab, Cisplatin, and Pemetrexed Disodium or Gemcitabine Hydrochloride may work better in treating patients with non-small cell lung cancer.
Detailed Description
PRIMARY OBJECTIVES: I. To estimate major pathologic response (mpCR) in patients with newly diagnosed and untreated non-small cell lung cancer (NSCLC) stage I-IIIA treated with three courses of induction nivolumab added to either cisplatin/pemetrexed or cisplatin/gemcitabine prior to surgery. SECONDARY OBJECTIVES: I. Safety. II. Complete pathologic response at all sites of disease. III. Major pathologic response rate at primary site. IV. Clinical complete response rate. V. 1 year progression free survival (PFS). VI. Overall survival. TERTIARY OBJECTIVES: I. To explore whether PDL1 expression is associated with treatment response. II. To explore whether there is a net change in the Th1/Th2 ratio (IFN-gamma, IL-4, IL10, etc.) or cell subset frequencies (M2 monocytes, myeloid-derived suppressor cells, etc.) within a patient's peripheral blood either at baseline or in response to treatment is associated with treatment response. III. To explore whether exosomes or other immune related serum biomarkers change after combination therapy. IV. To explore the predictive value of serial cell free deoxyribonucleic acid (DNA) levels and response. V. PD-L1 assessment in tumor.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Pathologically confirmed non small cell lung cancer (NSCLC), not previously treated, with a plan to undergo surgery
- •Stage I-IIIA (stage I tumors must be \>= 4 cm) per AJCC 8th edition
- •Tumor sample must be available for PD-L1 testing; archival tissue within 3 months of study enrollment will be used; if archival tissue is unavailable, a fresh biopsy will be taken
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- •While blood cells 2000/ul or more
- •Absolute neutrophil count 1500/ul or more
- •Platelets 100,000/ul or more
- •Hemoglobin 9 g/dl or more; (transfusion permitted)
- •Bilirubin less than or equal to 1.5 x the upper limit of normal (except subjects with Gilbert syndrome, who can have total bilirubin \< 3 mg/dl)
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 3 x the upper limit of normal
Exclusion Criteria
- •Patients who have participated in a study with an investigational agent or device within 2 weeks of enrollment
- •Any prior radiotherapy to the lung
- •Any prior treatment for NSCLC
- •Epidermal growth factor receptor (EGFR) or alkaline phosphatase (ALK) activating alteration
- •Any prior therapy with anti-PD-1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
- •Any history of a sever hypersensitivity reaction to any monoclonal antibody
- •Any history of allergy to the study drug components
- •Any concurrent malignancies- exceptions include- basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer or in situ cervical cancer that has undergone potentially curative therapy; patients with a history of other prior malignancy must have been treated with curative intent and must have remained disease-free for 3 years post-diagnosis
- •Participants with an active autoimmune disease or any other condition requiring systemic treatment with either corticosteroids within 14 days (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 30 days of randomization. Inhaled or topical steroids, and adrenal replacement steroid doses \> 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
- •Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.• Patients with evidence of interstitial lung disease or active, non-infectious pneumonitis. Patients with a history of interstitial lung disease or non-infectious pneumonitis requiring treatment with steroids are also excluded.
Arms & Interventions
Cohort I (nivolumab, cisplatin, pemetrexed disodium)
Patients with non-squamous lung cancer receive nivolumab IV over 30 minutes, cisplatin IV over 60-120 minutes, and pemetrexed disodium IV over 10 minutes on day 1. Courses repeat every 3 weeks for up to 9 weeks in the absence of disease progression or unacceptable toxicity
Intervention: Nivolumab
Cohort I (nivolumab, cisplatin, pemetrexed disodium)
Patients with non-squamous lung cancer receive nivolumab IV over 30 minutes, cisplatin IV over 60-120 minutes, and pemetrexed disodium IV over 10 minutes on day 1. Courses repeat every 3 weeks for up to 9 weeks in the absence of disease progression or unacceptable toxicity
Intervention: Cisplatin
Cohort I (nivolumab, cisplatin, pemetrexed disodium)
Patients with non-squamous lung cancer receive nivolumab IV over 30 minutes, cisplatin IV over 60-120 minutes, and pemetrexed disodium IV over 10 minutes on day 1. Courses repeat every 3 weeks for up to 9 weeks in the absence of disease progression or unacceptable toxicity
Intervention: Pemetrexed Disodium
Cohort I (nivolumab, cisplatin, gemcitabine hydrochloride)
Patients with squamous lung cancer receive nivolumab IV over 30 minutes on day 1, cisplatin IV over 60-120 minutes on day 1, and gemcitabine hydrochloride IV over 1 hour on days 1 and 8. Courses repeat every 3 weeks for up to 9 weeks in the absence of disease progression or unacceptable toxicity.
Intervention: Nivolumab
Cohort I (nivolumab, cisplatin, gemcitabine hydrochloride)
Patients with squamous lung cancer receive nivolumab IV over 30 minutes on day 1, cisplatin IV over 60-120 minutes on day 1, and gemcitabine hydrochloride IV over 1 hour on days 1 and 8. Courses repeat every 3 weeks for up to 9 weeks in the absence of disease progression or unacceptable toxicity.
Intervention: Gemcitabine Hydrochloride
Outcomes
Primary Outcomes
Major Pathologic Response (mpCR) Defined as < 10% Viable Tumor
Time Frame: Up to 63 days
For the primary endpoint, the major pathologic response rate was calculated as a percentage of patients who achieved a major pathologic response (i.e., \<10% viable tumor) or pathologic complete response. Then, the major pathologic response rate was tested with the exact binomial test under the null hypothesis that the true major pathologic response rate is ≤ 0.19. The corresponding 95% Clopper-Pearson confidence limits were reported too.
Secondary Outcomes
- Number of Adverse Events(Up to 6 months)
- Progression Free Survival(At 1 year)
- Overall Survival(Up to 1 year)
- Overall Clinical Response(At Week 10)
- Overall Clinical Response(At Month 3)
- Overall Clinical Response(At Month 6)