Brief Title
Single Agent Chemotherapy +/- Nivolumab in Patients With Advanced Squamous or Non-squamous NSCLC With Primary Resistance to Prior PD-1 or PDL-1 Inhibitor
Official Title
Randomized Phase II Trial of Single Agent Chemotherapy Plus Nivolumab or Single Agent Chemotherapy Alone in Patients With Advanced Squamous or Non-squamous NSCLC With Primary Resistance to Prior PD-1 or PDL-1 Inhibitor
Brief Summary
This is a randomized phase II study assessing the activity of single agent chemotherapy
combined with nivolumab (Arm A) compared to single agent chemotherapy alone (Arm B) in
squamous or non-squamous NSCLC subjects with primary resistance to prior PD-1 or PDL-1
inhibitor. The single agent chemotherapy chosen is at the discretion of the site investigator
and may include pemetrexed, gemcitabine or taxotere. Institutional standards should be used
for administration of the single agent chemotherapy. For both treatment arms, 21 days equals
1 cycle of therapy and subjects will be eligible to continue treatment until progressive
disease by RECIST v1.1 or unacceptable toxicity.
Upon registration, subjects will be randomized in a 1:1 ratio to either treatment with single
agent chemotherapy or single agent chemotherapy in combination with nivolumab. Randomization
is un-blinded and open-label; therefore there will be no placebo treatment for subjects
randomized to single agent chemotherapy
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Progression Free Survival (PFS), as Defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Secondary Outcome
Overall Response Rate (ORR) for Subjects on Each Treatment Arm, as Defined by RECIST 1.1 and Immune-related Response Criteria (irRECIST)
Condition
Non-Squamous Non-Small Cell Lung Cancer (NSCLC)
Intervention
Docetaxel
Study Arms / Comparison Groups
Arm A - Single Agent Chemotherapy + Nivolumab
Description: Single Agent Chemotherapy of choice plus nivolumab: Taxotere Pemetrexed Gemcitabine
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
3
Start Date
January 27, 2017
Completion Date
May 23, 2019
Primary Completion Date
May 23, 2019
Eligibility Criteria
Inclusion Criteria:
Subject must meet all of the following applicable inclusion criteria to participate in this
study:
1. Written informed consent and HIPAA authorization for release of personal health
information prior to registration. NOTE: HIPAA authorization may be included in the
informed consent or obtained separately.
2. Age ≥ 18 years at the time of consent.
3. ECOG Performance Status of 0-2 within 28 days prior to randomization.
4. Histological or cytological confirmed squamous or non-squamous non-small cell lung
cancer.
5. Measurable disease according to RECIST 1.1 within 28 days prior to randomization.
6. A subject with prior brain metastasis may be considered if they have completed their
treatment for brain metastasis at least 4 weeks prior to randomization, have been off
of corticosteroids for ≥ 2 weeks, and are asymptomatic.
7. Subjects must have primary resistance to PD-1 or PDL-1 inhibitors; defined as PD after
3 or fewer treatments with a PD-1 or PDL-1 inhibitor
8. Subjects must have progressed on or after previous platinum-based chemotherapy.
Chemotherapy may have previously been given with a PD-1 or PD-L1 inhibitor. Subjects
must have also progressed on or after receiving any PD-1 or PD-L1 inhibitor (including
nivolumab) as their most recent therapy.
9. Most recent PD-1 or PD-L1 inhibitor infusion must be completed at least 6 weeks of
randomization. The subject must have recovered from all reversible acute toxic effects
(other than alopecia) to ≤ Grade 1 or baseline.
10. Demonstrate adequate organ function as defined in the table below. All screening labs
to be obtained within 28 days prior to randomization.
White blood cell (WBC) ≥ 2 k/mm3 Absolute Neutrophil Count (ANC) ≥ 1.5 K/mm3
Hemoglobin (Hgb) ≥ 9 g/dL Platelet >100k Estimated creatinine clearance OR ≥ 40 cc/min
Serum creatinine ≤ 1.5 x upper limit of normal (ULN) Bilirubin 1.5 ≤ (ULN)2 Aspartate
aminotransferase (AST) ≤ 1.5 × ULN Alanine aminotransferase (ALT) ≤ 1.5 × ULN
International Normalized Ratio (INR) or Prothrombin Time (PT) Activated Partial
Thromboplastin Time (aPTT) ≤ 2 × ULN (Note: use of vitamin K antagonist is not
allowed)
11. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test
within 14 days prior to registration. These women must also have a negative serum or
urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within
24 hours prior to the start of Nivolumab then every 6 weeks thereafter. NOTE: Women
are considered of child bearing potential unless they are surgically sterile (have
undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are
post-menopausal. 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 62 must have a documented serum follicle stimulating hormone (FSH)
level less than 40 mIU/mL.
12. Women of childbearing potential must be willing to abstain from heterosexual activity
or use an effective method of contraception from the time of informed consent until 5
months after treatment discontinuation. Women cannot breast feed from the time of
informed consent to 5 months after last dose of study treatment. See below for
adequate methods of contraception.
13. Men who are sexually active with WOCBP must use any contraceptive method with a
failure rate of less than 1% per year. Men receiving Nivolumab and who are sexually
active with WOCBP will be instructed to adhere to contraception for a period of 7
months after the last dose of investigational product. See below for methods of
contraception.
14. As determined by the enrolling physician or protocol designee, ability of the subject
to understand and comply with study procedures for the entire length of the study
Exclusion Criteria
1. Prior treatment with the single agent chemotherapy the site investigator chooses to
use for this protocol (pemetrexed, taxotere or gemcitabine).
2. Previous autoimmune complication from PD-1 or PD-L1 requiring discontinuation of
therapy or treatment with steroids (ongoing treatment with more than 10 mg of
prednisone or steroid equivalent daily, excluding inhaled or topical steroids).
3. Previous discontinuation from PD-1 or PD-L1 due to an adverse event.
4. Any serious or uncontrolled medical disorder or active infection that would impair the
ability of the subject to receive protocol therapy.
5. Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the
mother is being treated on study).
6. Known additional malignancy that is active and/or progressive requiring treatment;
exceptions include basal cell or squamous cell skin cancer, in situ cervical or
bladder cancer, or other cancer for which the subject has been disease-free for at
least five years.
7. Active central nervous system (CNS) metastases. Subjects with brain metastases are
eligible if metastases have been treated and there is no magnetic resonance imaging
(MRI) evidence of progression for [lowest minimum is 4 weeks or more] after treatment
is complete and within 28 days prior to the first dose of Nivolumab administration.
There must also be no requirement for immunosuppressive doses of systemic
corticosteroids (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to
study drug administration.
8. Treatment with any investigational drug within 30 days prior to registration.
9. Subjects whose tumors express EGFR mutations on exons 19 and 21, ALK rearrangement, or
ROS1 rearrangement who still have other FDA approved targeted agents available for
treatment.
10. Subjects with an active or recent history of a known or suspected autoimmune disease
or recent history of a syndrome that required systemic
corticosteroids/immunosuppressive medications EXCEPT for syndromes which would not be
expected to recur in the absence of an external trigger. (Subjects with vitiligo,
autoimmune thyroiditis, or type I diabetes mellitus are permitted to enroll.)
11. As there is potential for hepatic toxicity with Nivolumab, drugs with a predisposition
to hepatoxicity should be used with caution in subjects treated with
Nivolumab-containing regimen.
12. Subjects should be excluded if they are positive test for hepatitis B virus surface
antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating
acute or chronic infection.
13. Subjects should be excluded if they have known history of testing positive for human
immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
14. History of allergy to study drug components.
15. Prior solid organ or stem cell transplant
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Nasser Hanna, M.D., ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT03041181
Organization ID
HCRN LUN15-233
Responsible Party
Sponsor-Investigator
Study Sponsor
Nasser Hanna, M.D.
Collaborators
Hoosier Cancer Research Network
Study Sponsor
Nasser Hanna, M.D., Principal Investigator, Hoosier Cancer Research Network
Verification Date
July 2022