Nivolumab in Treating Patients With Persistent, Recurrent, or Metastatic Cervical Cancer
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|ClinicalTrials.gov Identifier: NCT02257528|
Recruitment Status : Active, not recruiting
First Posted : October 6, 2014
Last Update Posted : December 5, 2018
|Condition or disease||Intervention/treatment||Phase|
|Cervical Adenocarcinoma Cervical Adenosquamous Carcinoma Recurrent Cervical Carcinoma Stage IV Cervical Cancer AJCC v6 and v7 Stage IVA Cervical Cancer AJCC v6 and v7 Stage IVB Cervical Cancer AJCC v6 and v7||Other: Laboratory Biomarker Analysis Biological: Nivolumab||Phase 2|
I. To assess the antitumor activity (proportion of objective response by Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 criteria) of nivolumab with objective tumor response in patients with persistent, recurrent or metastatic carcinoma of the cervix.
II. To determine the nature and degree of toxicity of nivolumab as assessed by Common Terminology Criteria for Adverse Events (CTCAE) in patients with persistent, recurrent or metastatic carcinoma of the cervix.
I. To estimate the duration of progression-free survival (PFS) and overall survival (OS).
I. To systematically evaluate programmed cell death (PD)-1 and B7 homolog 1 (B7-H1) (i.e., PD-1 ligand) expression in tumor infiltrating lymphocytes (TILs) and cervical cancer cells and explore their correlations with objective response, PFS, and OS in nivolumab-treated patients with PD-1 and B7-H1 scoring results.
II. To explore the composition of immune infiltrates in tumor specimens/biopsies from primary and/or metastatic/recurrent sites with selected markers including (but not limited) to cluster of differentiation (CD)4+, CD8+, forkhead box P3 (FoxP3), CD25, lymphocyte activation gene-3 (LAG-3), T cell immunoglobulin mucin-3 (TIM-3), and inducible T-cell co-stimulator (ICOS) and their correlations to objective response, PFS and OS in nivolumab-treated patients.
III. To evaluate human papillomavirus (HPV) status and to explore the changes of pre- and post-immune therapy responses to HPV16/18/31/35/45 E7 antigens in patients peripheral blood lymphocytes (PBL) and serum using proliferative and interferon (IFN)-gamma enzyme-linked immunospot (ELISPOT) (cellular immunity) and serological (enzyme-linked immunosorbent assay [ELISA]) assays.
IV. To explore the levels of circulating tumor cells (CTCs) pre-treatment and at 8 and 12 weeks and their association with patient outcome.
Patients receive nivolumab intravenously (IV) over approximately 60 minutes every 2 weeks for a maximum of 46 doses over 92 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||25 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Evaluation of Nivolumab, a Fully Human Antibody Against PD-1, in the Treatment of Persistent or Recurrent Cervical Cancer|
|Actual Study Start Date :||May 18, 2015|
|Estimated Primary Completion Date :||December 31, 2018|
Experimental: Treatment (nivolumab)
Patients receive nivolumab IV over approximately 60 minutes every 2 weeks for a maximum of 46 doses over 92 weeks in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
- Frequency of objective tumor response as assessed by RECIST 1.1 criteria [ Time Frame: Up to 5 years ]The efficacy of the study regimen will be measured by objective tumor response. Tumor response is dichotomized as response (i.e., complete or partial response) vs. non-response (i.e., stable disease, progressive disease, or indeterminate disease) and is assumed to have a Bernoulli distribution with a probability equal to pi.
- Incidence of adverse events as assessed by CTCAE version 4 [ Time Frame: Within 100 days of last protocol treatment ]The frequency and severity of adverse events as assessed by CTCAE version 4 and corresponding frequency table will be provided as descriptive statistics.
- PFS [ Time Frame: Time from study entry to time of progression or death, whichever occurs first, assessed up to 5 years ]Kaplan-Meier median estimates and curves will be used to describe PFS survival functions.
- OS [ Time Frame: Time from study entry to time of death or the date of last contact, assessed up to 5 years ]Kaplan-Meier median estimates and curves will be used to describe OS survival functions.
- Tumor expressions of PD-1 and PD-L1 in tumor infiltrating lymphocytes and cervical cancer cells [ Time Frame: Up to 5 years ]Spearman's correlation coefficient will be used to explore the associations of tumor expressions of PD-L1, PD-1 and other interested biomarkers with tumor response. Cox proportional hazards (PH) model will be utilized to evaluate the associations of these tumor expressions with PFS and OS. These expressions may also be dichotomized into high versus low values (cut at the median). Log-rank tests will be used to assess the associations of these dichotomized tumor expressions with PFS and OS. The corresponding hazard rations will be estimated by Cox PH models.
- Immune infiltration related biomarkers (i.e., CD4+, CD8+, FoxP3) in tumor specimens [ Time Frame: Up to 5 years ]Immune infiltration related biomarkers (i.e., CD4+, CD8+, FoxP3) in tumor specimens will be associated with objective tumor response, PFS and OS in nivolumab-treated patients.
- Change in the immune response to HPV 16/18/31/35/45 E7 antigen in peripheral blood lymphocytes and serum [ Time Frame: Baseline to up to 5 years ]Wilcoxon signed rank test (for interval or ordinal data) or McNemar's test (for binary data) may be utilized to examine whether the study treatment will change immune response to HPV 16/18/31/35/45 E7 antigen in peripheral blood lymphocytes and serum by changes in the measures of pre- and post-treatment immune response to HPV 16/18/31/35/45 E7.
- Change in the CTC count [ Time Frame: Baseline to up to 12 weeks ]Change in the CTC count and whether the CTC count is associated with objective response, PFS and OS in nivolumab-treated patients will be evaluated.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02257528
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|Principal Investigator:||Alessandro Santin||NRG Oncology|