A Dose Frequency Optimization Study with Nivolumab Every 2 Weeks vsNivolumab Every 4 Weeks in advanced NSCLC patients Who Received 4 Months of Nivolumab Every 2 Weeks
- Conditions
- Advanced or Metastatic Non-small Cell Lung CancerMedDRA version: 19.0Level: PTClassification code 10059515Term: Non-small cell lung cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-004633-27-ES
- Lead Sponsor
- Bristol-Myers Squibb International Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 620
1. Signed Written Informed Consent
a) Subjects must have signed and dated an IRB/IEC-approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal
subject care.
b) Subjects must be willing and able to comply with scheduled visits, treatment schedule,laboratory tests, and other requirements of the study.
2. Target Population
a) Subjects with histologically or cytologically documented Sq- or non-SqNSCLC who present with Stage IIIB/Stage IV disease (according to version 7 of the International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology), or with recurrent or progressive disease following multimodal therapy (radiation therapy, surgical resection, or definitive chemoradiotherapy for locally advanced disease).
b) Subjects must have received and tolerated nivolumab 3 mg/kg or 240 mg every 2 weeks for approximately 4 months (16 weeks ± 2 weeks). Subjects may continue to receive pre-study nivolumab treatment during screening assessments as noted in Table 5.1-2 of the protocol.
c) Subjects must have at least 2 tumor assessments after the start of nivolumab and must demonstrate CR, PR, or SD to the pre-study nivolumab treatment on the latest scan within 28 days prior to randomization.
d) Subjects must have had measurable disease by CT or MRI per RECIST 1.1 criteria at the time of starting first dose of pre-study nivolumab treatment.
e) As of Amendment 01, this criterion is no longer applicable.
f) ECOG PS 0-2
g) Subjects with stable CNS metastases if CNS metastases are treated and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to enrollment. In addition, subjects must be either off corticosteroids or on a stable or decreasing dose of < 10 mg daily prednisone (or equivalent).
h) All baseline laboratory requirements will be assessed and should be obtained within 14 days (unless otherwise specified in Table 5.1-1) of first dose of randomized nivolumab. Screening laboratory values must meet the following criteria:
i) WBCs >= 2000/uL
ii) Neutrophils >= 1500/uL
iii) Platelets >= 100 x 10³/uL
iv) Hemoglobin >= 9.0 g/dL
v) Serum creatinine of <=1.5 X ULN or creatinine clearance > 40 mL/minute (using cockcroft/Gault formula)
vi) AST <= 3X ULN
vii) ALT <= 3X ULN
viii) Total bilirubin <= 1.5X ULN (except subjects with Gilbert Syndrome who must have total bilirubin < 3.0 mg/dL)
i) Palliative radiotherapy must be completed at least 2 weeks prior to enrollment.
j) Subject Re-enrollment: This study permits the re-enrollment of a subject that has discontinued the study as a pre-treatment failure (ie, subject has not been randomized/has not been treated). If re-enrolled, the subject must be re-consented.
3. Age and Reproductive Status
a) Males and Females, >=18 years of age.
b) Women of childbearing potential (WOCBP) must 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 study drug.
c) Women must not be breastfeeding.
d) WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with nivolumab plus 5 half-lives of nivolumab (125 days) plus 30 days (duration of ovulatory cycle) for a total of 155 days or 23 weeks post-treatment completion.
e) Males who are sexu
1. Target Disease Exceptions
a) Subjects with carcinomatous meningitis.
b) Subjects with untreated, symptomatic central nervous system (CNS) metastases are excluded.
2. Medical History and Concurrent Diseases
Subjects with interstitial lung disease (eg, sarcoidosis) that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity. Subjects with chronic obstructive pulmonary disease whose disease is controlled at study entry are allowed.
b) Subjects with an active, known or suspected autoimmune disease. Subjects 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.
c) Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of first randomized dose of study drug with the exception of the subjects allowed to enroll with treated or active CNS metastases requiring steroids. Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
d) Subjects who received prior therapy with an anti-CTLA-4, anti-PD-L1, or anti-PD-L2, anti-CT137 (or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways, except pre-study nivolumab) or subject is expected to require any other form of systemic antineoplastic therapy while receiving nivolumab.
e) Any other serious or uncontrolled medical disorder, active infection, physical exam finding, laboratory finding, altered mental status, or psychiatric condition that, in the opinion of the investigator, would limit the subject?s ability to comply with the study requirements, substantially increase the risk to the subject, or impact the interpretability of study results.
f) Other active malignancy requiring concurrent intervention.
g) Subjects with previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, endometrial, cervical/dysplasia, melanoma, or breast) are excluded unless a complete remission was achieved at least 2 years prior to study entry AND no additional therapy is required during the study period with the exception of anti-estrogen/androgen therapy or bisphosphonates.
h) All toxicities attributed to prior anti-cancer therapy other than alopecia, fatigue, or peripheral neuropathy must have resolved to Grade 1 (NCI CTCAE version 4) or baseline before administration of study drug.
i) Subjects must have recovered from the effects of major surgery or significant traumatic injury at least 14 days before the first dose of study treatment.
j) As of Amendment 01, this criterion has been moved to 3b.
3. Physical and Laboratory Test Findings
a) Positive for Hepatitis B virus or Hepatitis C virus indicating acute or chronic infection.
b) Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). NOTE: Testing for HIV must be performed at sites where mandated by local regulation
4. Allergies and Adverse Drug Reaction
a) History of severe hypersensitivity reactions to other monoclonal antibodies.
5. Other Exclusion Criteria
a) Prisoners or subjects who are involuntarily incarcerat
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method