Description:
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.
Title
- Brief Title: 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
- Official Title: Nivolumab Plus Cisplatin/Pemetrexed or Cisplatin/Gemcitabine as Induction in Resectable Non-Small Cell Lung Cancer
Clinical Trial IDs
- ORG STUDY ID:
17P.556
- NCT ID:
NCT03366766
Conditions
- Non-Squamous Non-Small Cell Lung Carcinoma
- Stage I Non-Small Cell Lung Cancer
- Stage IA Non-Small Cell Lung Carcinoma
- Stage IB Non-Small Cell Lung Carcinoma
- Stage II Non-Small Cell Lung Cancer
- Stage IIA Non-Small Cell Lung Carcinoma
- Stage IIB Non-Small Cell Lung Carcinoma
- Stage IIIA Non-Small Cell Lung Cancer
Interventions
Drug | Synonyms | Arms |
---|
Nivolumab | BMS-936558, NIVO, Opdivo, ONO-4538 | Cohort I (nivolumab, cisplatin, gemcitabine hydrochloride) |
Cisplatin | (SP-4-2)-Diamminedichloroplatinum, Abiplatin, Blastolem, Briplatin, (CDDP) Cis-diammine-dichloroplatinum, Cis-dichloroammine Platinum (II), Metaplatin, Plastistil, Platinol, Platinex, Platinol-AQ VHA Plus, Peyrone's Salt | Cohort I (nivolumab, cisplatin, pemetrexed disodium) |
Pemetrexed Disodium | Alimta, N-[4-[2-(2-Amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic Acid Disodium Salt | Cohort I (nivolumab, cisplatin, pemetrexed disodium) |
Gemcitabine Hydrochloride | Hydrochloride, Difluorodeoxycytidine Hydrochloride, Gemzar | Cohort I (nivolumab, cisplatin, gemcitabine hydrochloride) |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Cohort I (nivolumab, cisplatin, pemetrexed disodium) | Experimental | 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 | - Nivolumab
- Cisplatin
- Pemetrexed Disodium
|
Cohort I (nivolumab, cisplatin, gemcitabine hydrochloride) | Experimental | 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. | - Nivolumab
- Gemcitabine Hydrochloride
|
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
- Glomerular filtration rate (GFR) greater than or equal to 40 ml/min using the
Cockcroft-Gault formula or serum creatinine less than or equal to 1.5 x (ULN) upper
limit of normal
- Women of reproductive potential should have a negative serum or urine pregnancy test
(minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin
[HCG]) within 21 days of the study enrollment
- Women of reproductive potential must use highly effective contraception methods to
avoid pregnancy for 23 weeks after the last dose of study drugs; "women of
reproductive potential" is defined as any female who has experienced menarche and who
has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or
who is not postmenopausal; menopause is defined clinically as 12 months of amenorrhea
in a woman over 45 in the absence of other biological or physiological causes; in
addition, women under the age of 55 must have a documented serum follicle stimulating
hormone (FSH) level more than 40 mIU/mL
- Men of reproductive potential who are sexually active with women of reproductive
potential must use any contraceptive method with a failure rate of less than 1% per
year; men who are receiving the study medications will be instructed to adhere to
contraception for 31 weeks after the last dose of study drugs; men who are azoospermic
do not require contraception
- All subjects must be able to comprehend and sign a written informed consent document
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.
- Patients with a known human immunodeficiency virus infection (HIV 1/2 antibodies) or
acquired immunodeficiency syndrome (HIV/AIDS), active hepatitis B (e.g., hepatitis B
surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV]
ribonucleic acid [RNA] [qualitative] is detected)
- Patients who have received a live vaccine within 30 days prior initiation of the
systemic regimen
- Patients must not be receiving any other investigational agents
- Patients with uncontrolled intercurrent illnesses including, but not limited to an
active infection requiring systemic therapy or a known psychiatric or substance abuse
disorder(s) that would interfere with cooperation with the requirements of the trial
- Women must not be pregnant (as above) or breastfeeding
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Major pathologic response (mpCR) defined as < 10% viable tumor |
Time Frame: | Up to 63 days |
Safety Issue: | |
Description: | A minimax Simon two-stage design will be used. The mpCR rate and its associated score 95% confidence interval will be estimated using the methods |
Secondary Outcome Measures
Measure: | Incidence of adverse events according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 |
Time Frame: | Up to 6 months |
Safety Issue: | |
Description: | Safety data will be summarized descriptively. |
Measure: | Progression free survival |
Time Frame: | At 1 year |
Safety Issue: | |
Description: | The distribution of progression-free survival will be estimated using the Kaplan-Meier method. |
Measure: | Overall survival |
Time Frame: | Up to 6 months |
Safety Issue: | |
Description: | The distribution of overall survival will be estimated using the Kaplan-Meier method. |
Measure: | Overall clinical response |
Time Frame: | Up to 6 months |
Safety Issue: | |
Description: | Will be summarized by presence of baseline measurable disease. |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | Sidney Kimmel Cancer Center at Thomas Jefferson University |
Last Updated
March 5, 2021