Nivolumab in Treating Patients With Persistent, Recurrent, or Metastatic Cervical Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02257528
• Collaborator: NRG Oncology (Other)
• Enrollment: 26
• Locations: 337
• Arm: 1
• Patients Per Site: 0.1

Study Details

Study Description

Brief Summary

This phase II trial studies the side effects and how well nivolumab works in treating patients with cervical cancer that has grown, come back, or spread to other places in the body. Monoclonal antibodies, such as nivolumab, may block tumor growth in different ways by targeting certain cells.

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

Detailed Description

PRIMARY OBJECTIVES:

1. 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.

2. 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.

SECONDARY OBJECTIVES:

1. To estimate the duration of progression-free survival (PFS) and overall survival (OS).

TERTIARY OBJECTIVES:

1. 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.

2. 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.

3. 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.

4. To explore the levels of circulating tumor cells (CTCs) pre-treatment and at 8 and 12 weeks and their association with patient outcome.

OUTLINE:

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 Design

• Study Type: Interventional
• Actual Enrollment: 26 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Primary Completion Date: Mar 5, 2019

Arms and Interventions

Arm	Intervention/Treatment
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; Correlative studies; Biological: Nivolumab; Given IV; Other Names: BMS-936558 CMAB819 MDX-1106 NIVO Nivolumab Biosimilar CMAB819 ONO-4538 Opdivo

Outcome Measures

Primary Outcome Measures

1. Objective Tumor Response as Assessed by RECIST 1.1 Criteria [The average of study treatment time was 3.8 months.]

   Proportion of participants with objective tumor response. Objective tumor response is defined as complete or partial tumor response assessed by RECIST 1.1.

2. Adverse Events (Grade 3 or Higher) During Treatment Period as Assessed by CTCAE Version 4 [Within 100 days of last protocol treatment]

   Number of participants with a maximum grade of 3 or higher during treatment period. Adverse events are graded and categorized using CTCAE v4.0.

Secondary Outcome Measures

1. Progression-free Survival [Time from study entry to time of progression or death, whichever occurs first, up to 5 years of follow-up.]

   Progression-free survival is the period of time from study entry to time of disease progression, death or date of last contact, whichever occurs first. Progression is assessed by RECIST 1.1.

2. Overall Survival [Time from study entry to time of death or the date of last contact, up to 5 years of follow-up]

   Overall survival is defined as the duration of time from study entry to time of death or the date of last contact.

Other Outcome Measures

1. Tumor Expressions of PD-1 and PD-L1 in Tumor Infiltrating Lymphocytes and Cervical Cancer Cells [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.

2. Immune Infiltration Related Biomarkers (i.e., CD4+, CD8+, FoxP3) in Tumor Specimens [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.

3. Change in the Immune Response to HPV 16/18/31/35/45 E7 Antigen in Peripheral Blood Lymphocytes and Serum [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.

4. Change in the CTC Count [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients must have persistent, recurrent or metastatic squamous cell carcinoma, adenosquamous carcinoma or adenocarcinoma of the cervix with documented disease progression (disease not amendable to curative therapy); NOTE: the following cervical tumors are not eligible: minimal deviation/adenoma malignum, gastric type adenocarcinoma, clear cell carcinoma and mesonephric carcinoma; histologic confirmation of the original primary tumor is required via the pathology report

• All patents must have measurable disease as defined by RECIST 1.1; measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be >= 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI) or caliper measurement by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodes must be >= 15 mm in short axis when measured by CT or MRI

• Patients must have at least one "target" lesion" to be used to assess response on this protocol as defined by RECIST 1.1; tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy

• Appropriate for study entry based on the following diagnostic workup:

• History/physical examination within 28 days prior to registration

• Imaging of target lesion(s) within 28 days prior to registration

• Further protocol-specific assessments:

• Recovery from adverse effects of recent surgery, radiotherapy or chemotherapy

• Any other prior therapy directed at the malignant tumor including chemotherapy, biologic/targeted agents and immunologic agents must be discontinued at least three weeks prior to registration

• Investigation agents must be discontinued for at least 30 days prior to registration

• Any prior radiation therapy must be completed at least 4 weeks prior to registration

• At least 4 weeks must have elapsed since any major surgery prior to registration

• Patients must have had one prior systemic chemotherapeutic regimen for management of persistent, recurrent or metastatic carcinoma of the cervix (e.g.; paclitaxel/cisplatin, paclitaxel/cisplatin/bevacizumab); chemotherapy administered concurrent with primary radiation (e.g.; weekly cisplatin) is not counted as a systemic chemotherapy regimen; adjuvant chemotherapy given following the completion of radiation therapy (or concurrent chemotherapy and radiation therapy) is not counted as a systemic chemotherapy regimen (e.g.; paclitaxel and carboplatin for up to 4 cycles); NOTE: patients who have received more than one prior regimen are NOT eligible

• Performance status of 0 or 1

• Absolute neutrophil count (ANC) >= 1,500/ul

• Platelets >= 100,000/ul

• Creatinine =< 1.5 x institutional upper limit of normal (ULN) or creatinine clearance (CrCl) >= 40 mL/min using Cockcroft-Gault formula

• Bilirubin =< 1.5 x ULN

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN

• Normal thyroid function testing (thyroid stimulating hormone [TSH]) within 14 days prior to registration

• The patient or a legally authorized representative must provide study-specific informed consent authorization permitting release of personal health information prior to study entry

Exclusion Criteria:

• Patients who have had prior therapy with nivolumab or with an anti-PD-1, anti-PD-ligand (L)1, anti-PD-L2, anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune check point pathways

• History of severe hypersensitivity reaction to any monoclonal antibody

• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years

• Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure and unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• Patients who are pregnant or nursing; women of child-bearing potential (WOCBP) must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; WOCBP should use an adequate method to avoid pregnancy for 23 weeks after the last dose of investigational drug; WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IV/L or equivalent units of human chorionic gonadotropin [HCG]) within 24 hours prior to the start of nivolumab; women must not be breastfeeding

• Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile or have undergone definitive radiation) do not require contraception

• Women of childbearing potential (WOCBP) is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy of bilateral oophorectomy) or who is not postmenopausal; menopause is defined clinically as 12 month 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 greater than 40 mIU/mL

• WOCBP receiving nivolumab will be instructed to adhere to contraception for a period of 23 weeks after the last dose of investigational product

• Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform the treating physician immediately

• Patients with known brain metastases or leptomeningeal metastases are excluded unless the following conditions are met:

• Metastases have been treated and there is no magnetic resonance imaging (MRI) evidence of progression for at least 4 weeks after treatment is complete (must be confirmed 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

• Patients should be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)

• Patients should be excluded if they have a positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection

• Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids, should be excluded; these include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IRB), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded; patient with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible; patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible

• NOTE: patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (precipitating event)

• Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration; inhaled or topical steroids and adrenal replacement doses =< 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease; patients are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption); physiologic replacement doses of systemic corticosteroids are permitted, even if =< 10 mg/day prednisone equivalents; a brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted

• Patients who have had evidence of active or acute diverticulitis, intra-abdominal abscess, abdominal/pelvic fistula, gastrointestinal perforation, gastrointestinal (GI) obstruction and/or who require parenteral hydration and/or nutrition

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama	United States	35233
2	Anchorage Associates in Radiation Medicine	Anchorage	Alaska	United States	98508
3	Anchorage Radiation Therapy Center	Anchorage	Alaska	United States	99504
4	Alaska Breast Care and Surgery LLC	Anchorage	Alaska	United States	99508
5	Alaska Oncology and Hematology LLC	Anchorage	Alaska	United States	99508
6	Alaska Regional Hospital	Anchorage	Alaska	United States	99508
7	Alaska Women's Cancer Care	Anchorage	Alaska	United States	99508
8	Anchorage Oncology Centre	Anchorage	Alaska	United States	99508
9	Katmai Oncology Group	Anchorage	Alaska	United States	99508
10	Providence Alaska Medical Center	Anchorage	Alaska	United States	99508
11	CHI Saint Vincent Cancer Center Hot Springs	Hot Springs	Arkansas	United States	71913
12	Sutter Auburn Faith Hospital	Auburn	California	United States	95602
13	Sutter Cancer Centers Radiation Oncology Services-Auburn	Auburn	California	United States	95603
14	Kaiser Permanente-Baldwin Park	Baldwin Park	California	United States	91706
15	Alta Bates Summit Medical Center-Herrick Campus	Berkeley	California	United States	94704
16	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California	United States	91505
17	Mills-Peninsula Medical Center	Burlingame	California	United States	94010
18	Sutter Cancer Centers Radiation Oncology Services-Cameron Park	Cameron Park	California	United States	95682
19	Eden Hospital Medical Center	Castro Valley	California	United States	94546
20	Sutter Davis Hospital	Davis	California	United States	95616
21	UC San Diego Moores Cancer Center	La Jolla	California	United States	92093
22	Memorial Medical Center	Modesto	California	United States	95355
23	Palo Alto Medical Foundation-Camino Division	Mountain View	California	United States	94040
24	Palo Alto Medical Foundation-Gynecologic Oncology	Mountain View	California	United States	94040
25	Palo Alto Medical Foundation Health Care	Palo Alto	California	United States	94301
26	Sutter Cancer Centers Radiation Oncology Services-Roseville	Roseville	California	United States	95661
27	Sutter Roseville Medical Center	Roseville	California	United States	95661
28	Sutter Medical Center Sacramento	Sacramento	California	United States	95816
29	Kaiser Permanente-San Diego Mission	San Diego	California	United States	92108
30	Kaiser Permanente-San Diego Zion	San Diego	California	United States	92120
31	California Pacific Medical Center-Pacific Campus	San Francisco	California	United States	94115
32	Kaiser Permanente-San Marcos	San Marcos	California	United States	92078
33	Palo Alto Medical Foundation-Santa Cruz	Santa Cruz	California	United States	95065
34	Sutter Pacific Medical Foundation	Santa Rosa	California	United States	95403
35	Palo Alto Medical Foundation-Sunnyvale	Sunnyvale	California	United States	94086
36	Sutter Cancer Centers Radiation Oncology Services-Vacaville	Vacaville	California	United States	95687
37	Sutter Solano Medical Center/Cancer Center	Vallejo	California	United States	94589
38	Yale University	New Haven	Connecticut	United States	06520
39	Beebe Medical Center	Lewes	Delaware	United States	19958
40	Christiana Gynecologic Oncology LLC	Newark	Delaware	United States	19713
41	Delaware Clinical and Laboratory Physicians PA	Newark	Delaware	United States	19713
42	Helen F Graham Cancer Center	Newark	Delaware	United States	19713
43	Medical Oncology Hematology Consultants PA	Newark	Delaware	United States	19713
44	Christiana Care Health System-Christiana Hospital	Newark	Delaware	United States	19718
45	Beebe Health Campus	Rehoboth Beach	Delaware	United States	19971
46	TidalHealth Nanticoke / Allen Cancer Center	Seaford	Delaware	United States	19973
47	Christiana Care Health System-Wilmington Hospital	Wilmington	Delaware	United States	19801
48	Low Country Cancer Care	Savannah	Georgia	United States	31404
49	Memorial Health University Medical Center	Savannah	Georgia	United States	31404
50	Summit Cancer Care-Memorial	Savannah	Georgia	United States	31404
51	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia	United States	31405
52	Saint Luke's Cancer Institute - Boise	Boise	Idaho	United States	83712
53	Kootenai Health - Coeur d'Alene	Coeur d'Alene	Idaho	United States	83814
54	Saint Luke's Cancer Institute - Fruitland	Fruitland	Idaho	United States	83619
55	Saint Luke's Cancer Institute - Meridian	Meridian	Idaho	United States	83642
56	Saint Luke's Cancer Institute - Nampa	Nampa	Idaho	United States	83686
57	Kootenai Clinic Cancer Services - Post Falls	Post Falls	Idaho	United States	83854
58	Kootenai Cancer Clinic	Sandpoint	Idaho	United States	83864
59	Saint Luke's Cancer Institute - Twin Falls	Twin Falls	Idaho	United States	83301
60	Saint Joseph Medical Center	Bloomington	Illinois	United States	61701
61	Illinois CancerCare-Bloomington	Bloomington	Illinois	United States	61704
62	Illinois CancerCare-Canton	Canton	Illinois	United States	61520
63	Memorial Hospital of Carbondale	Carbondale	Illinois	United States	62902
64	Illinois CancerCare-Carthage	Carthage	Illinois	United States	62321
65	Centralia Oncology Clinic	Centralia	Illinois	United States	62801
66	Northwestern University	Chicago	Illinois	United States	60611
67	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois	United States	62526
68	Decatur Memorial Hospital	Decatur	Illinois	United States	62526
69	Crossroads Cancer Center	Effingham	Illinois	United States	62401
70	Illinois CancerCare-Eureka	Eureka	Illinois	United States	61530
71	Illinois CancerCare-Galesburg	Galesburg	Illinois	United States	61401
72	Western Illinois Cancer Treatment Center	Galesburg	Illinois	United States	61401
73	Sudarshan K Sharma MD Limited-Gynecologic Oncology	Hinsdale	Illinois	United States	60521
74	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois	United States	61443
75	Illinois CancerCare-Macomb	Macomb	Illinois	United States	61455
76	Good Samaritan Regional Health Center	Mount Vernon	Illinois	United States	62864
77	Cancer Care Center of O'Fallon	O'Fallon	Illinois	United States	62269
78	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois	United States	61350
79	Radiation Oncology of Northern Illinois	Ottawa	Illinois	United States	61350
80	Illinois CancerCare-Pekin	Pekin	Illinois	United States	61554
81	OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center	Pekin	Illinois	United States	61554
82	Illinois CancerCare-Peoria	Peoria	Illinois	United States	61615
83	OSF Saint Francis Radiation Oncology at Peoria Cancer Center	Peoria	Illinois	United States	61615
84	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
85	OSF Saint Francis Medical Center	Peoria	Illinois	United States	61637
86	Illinois CancerCare-Peru	Peru	Illinois	United States	61354
87	Valley Radiation Oncology	Peru	Illinois	United States	61354
88	Illinois CancerCare-Princeton	Princeton	Illinois	United States	61356
89	Central Illinois Hematology Oncology Center	Springfield	Illinois	United States	62702
90	Southern Illinois University School of Medicine	Springfield	Illinois	United States	62702
91	Springfield Clinic	Springfield	Illinois	United States	62702
92	Memorial Medical Center	Springfield	Illinois	United States	62781
93	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana	United States	46202
94	Sidney and Lois Eskenazi Hospital	Indianapolis	Indiana	United States	46202
95	Reid Health	Richmond	Indiana	United States	47374
96	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa	United States	50325
97	Mercy Cancer Center-West Lakes	Clive	Iowa	United States	50325
98	Alegent Health Mercy Hospital	Council Bluffs	Iowa	United States	51503
99	Greater Regional Medical Center	Creston	Iowa	United States	50801
100	Medical Oncology and Hematology Associates-Laurel	Des Moines	Iowa	United States	50314
101	Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
102	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa	United States	52242
103	Mercy Medical Center-West Lakes	West Des Moines	Iowa	United States	50266
104	Cancer Center of Kansas - Chanute	Chanute	Kansas	United States	66720
105	Cancer Center of Kansas - Dodge City	Dodge City	Kansas	United States	67801
106	Cancer Center of Kansas - El Dorado	El Dorado	Kansas	United States	67042
107	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas	United States	66701
108	Cancer Center of Kansas-Independence	Independence	Kansas	United States	67301
109	Cancer Center of Kansas-Kingman	Kingman	Kansas	United States	67068
110	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
111	Cancer Center of Kansas-Liberal	Liberal	Kansas	United States	67905
112	Cancer Center of Kansas - Newton	Newton	Kansas	United States	67114
113	Cancer Center of Kansas - Parsons	Parsons	Kansas	United States	67357
114	Cancer Center of Kansas - Pratt	Pratt	Kansas	United States	67124
115	Cancer Center of Kansas - Salina	Salina	Kansas	United States	67401
116	Cancer Center of Kansas - Wellington	Wellington	Kansas	United States	67152
117	Associates In Womens Health	Wichita	Kansas	United States	67208
118	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas	United States	67208
119	Ascension Via Christi Hospitals Wichita	Wichita	Kansas	United States	67214
120	Cancer Center of Kansas - Wichita	Wichita	Kansas	United States	67214
121	Cancer Center of Kansas - Winfield	Winfield	Kansas	United States	67156
122	Flaget Memorial Hospital	Bardstown	Kentucky	United States	40004
123	Commonwealth Cancer Center-Corbin	Corbin	Kentucky	United States	40701
124	Saint Joseph Radiation Oncology Resource Center	Lexington	Kentucky	United States	40504
125	Saint Joseph Hospital East	Lexington	Kentucky	United States	40509
126	Jewish Hospital	Louisville	Kentucky	United States	40202
127	Saints Mary and Elizabeth Hospital	Louisville	Kentucky	United States	40215
128	UofL Health Medical Center Northeast	Louisville	Kentucky	United States	40245
129	Jewish Hospital Medical Center South	Shepherdsville	Kentucky	United States	40165
130	Maine Medical Center- Scarborough Campus	Scarborough	Maine	United States	04074
131	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland	United States	21287
132	Massachusetts General Hospital Cancer Center	Boston	Massachusetts	United States	02114
133	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
134	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
135	Lahey Hospital and Medical Center	Burlington	Massachusetts	United States	01805
136	Henry Ford Cancer Institute-Downriver	Brownstown	Michigan	United States	48183
137	Henry Ford Macomb Hospital-Clinton Township	Clinton Township	Michigan	United States	48038
138	Henry Ford Medical Center-Fairlane	Dearborn	Michigan	United States	48126
139	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan	United States	48201
140	Henry Ford Hospital	Detroit	Michigan	United States	48202
141	Weisberg Cancer Treatment Center	Farmington Hills	Michigan	United States	48334
142	Henry Ford Medical Center-Columbus	Novi	Michigan	United States	48377
143	Henry Ford West Bloomfield Hospital	West Bloomfield	Michigan	United States	48322
144	Central Care Cancer Center - Bolivar	Bolivar	Missouri	United States	65613
145	Parkland Health Center-Bonne Terre	Bonne Terre	Missouri	United States	63628
146	Cox Cancer Center Branson	Branson	Missouri	United States	65616
147	Saint Francis Medical Center	Cape Girardeau	Missouri	United States	63703
148	Southeast Cancer Center	Cape Girardeau	Missouri	United States	63703
149	Capital Region Southwest Campus	Jefferson City	Missouri	United States	65109
150	Freeman Health System	Joplin	Missouri	United States	64804
151	Mercy Hospital Joplin	Joplin	Missouri	United States	64804
152	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri	United States	65401
153	Mercy Clinic-Rolla-Cancer and Hematology	Rolla	Missouri	United States	65401
154	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri	United States	63109
155	Missouri Baptist Medical Center	Saint Louis	Missouri	United States	63131
156	Mercy Hospital Saint Louis	Saint Louis	Missouri	United States	63141
157	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	Missouri	United States	63670
158	Mercy Hospital Springfield	Springfield	Missouri	United States	65804
159	CoxHealth South Hospital	Springfield	Missouri	United States	65807
160	Missouri Baptist Sullivan Hospital	Sullivan	Missouri	United States	63080
161	Missouri Baptist Outpatient Center-Sunset Hills	Sunset Hills	Missouri	United States	63127
162	Community Hospital of Anaconda	Anaconda	Montana	United States	59711
163	Billings Clinic Cancer Center	Billings	Montana	United States	59101
164	Saint Vincent Healthcare	Billings	Montana	United States	59101
165	Bozeman Deaconess Hospital	Bozeman	Montana	United States	59715
166	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana	United States	59701
167	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana	United States	59405
168	Great Falls Clinic	Great Falls	Montana	United States	59405
169	Saint Peter's Community Hospital	Helena	Montana	United States	59601
170	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
171	Saint Patrick Hospital - Community Hospital	Missoula	Montana	United States	59802
172	Community Medical Hospital	Missoula	Montana	United States	59804
173	CHI Health Saint Francis	Grand Island	Nebraska	United States	68803
174	Heartland Hematology and Oncology	Kearney	Nebraska	United States	68845
175	CHI Health Good Samaritan	Kearney	Nebraska	United States	68847
176	Saint Elizabeth Regional Medical Center	Lincoln	Nebraska	United States	68510
177	Alegent Health Immanuel Medical Center	Omaha	Nebraska	United States	68122
178	Hematology and Oncology Consultants PC	Omaha	Nebraska	United States	68122
179	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska	United States	68124
180	Alegent Health Lakeside Hospital	Omaha	Nebraska	United States	68130
181	Creighton University Medical Center	Omaha	Nebraska	United States	68131
182	Midlands Community Hospital	Papillion	Nebraska	United States	68046
183	Women's Cancer Center of Nevada	Las Vegas	Nevada	United States	89106
184	Cooper Hospital University Medical Center	Camden	New Jersey	United States	08103
185	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
186	MD Anderson Cancer Center at Cooper-Voorhees	Voorhees	New Jersey	United States	08043
187	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87102
188	Southwest Gynecologic Oncology Associates Inc	Albuquerque	New Mexico	United States	87106
189	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
190	Sampson Radiation Oncology	Clinton	North Carolina	United States	28328
191	Southeastern Medical Oncology Center-Clinton	Clinton	North Carolina	United States	28328
192	Southeastern Medical Oncology Center-Goldsboro	Goldsboro	North Carolina	United States	27534
193	Wayne Memorial Hospital	Goldsboro	North Carolina	United States	27534
194	Wayne Radiation Oncology	Goldsboro	North Carolina	United States	27534
195	Onslow Memorial Hospital	Jacksonville	North Carolina	United States	28546
196	Southeastern Medical Oncology Center-Jacksonville	Jacksonville	North Carolina	United States	28546
197	UHHS-Chagrin Highlands Medical Center	Beachwood	Ohio	United States	44122
198	Strecker Cancer Center-Belpre	Belpre	Ohio	United States	45714
199	Dayton Physicians LLC-Miami Valley South	Centerville	Ohio	United States	45459
200	Miami Valley Hospital South	Centerville	Ohio	United States	45459
201	Adena Regional Medical Center	Chillicothe	Ohio	United States	45601
202	Good Samaritan Hospital - Cincinnati	Cincinnati	Ohio	United States	45220
203	Oncology Hematology Care Inc-Kenwood	Cincinnati	Ohio	United States	45236
204	Bethesda North Hospital	Cincinnati	Ohio	United States	45242
205	TriHealth Cancer Institute-Westside	Cincinnati	Ohio	United States	45247
206	TriHealth Cancer Institute-Anderson	Cincinnati	Ohio	United States	45255
207	Case Western Reserve University	Cleveland	Ohio	United States	44106
208	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio	United States	44111
209	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
210	Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210
211	Mount Carmel East Hospital	Columbus	Ohio	United States	43213
212	Columbus Oncology and Hematology Associates Inc	Columbus	Ohio	United States	43214
213	Riverside Methodist Hospital	Columbus	Ohio	United States	43214
214	Grant Medical Center	Columbus	Ohio	United States	43215
215	The Mark H Zangmeister Center	Columbus	Ohio	United States	43219
216	Mount Carmel Health Center West	Columbus	Ohio	United States	43222
217	Doctors Hospital	Columbus	Ohio	United States	43228
218	Good Samaritan Hospital - Dayton	Dayton	Ohio	United States	45406
219	Miami Valley Hospital	Dayton	Ohio	United States	45409
220	Dayton Physician LLC-Miami Valley Hospital North	Dayton	Ohio	United States	45415
221	Miami Valley Hospital North	Dayton	Ohio	United States	45415
222	Delaware Health Center-Grady Cancer Center	Delaware	Ohio	United States	43015
223	Delaware Radiation Oncology	Delaware	Ohio	United States	43015
224	Grady Memorial Hospital	Delaware	Ohio	United States	43015
225	Armes Family Cancer Center	Findlay	Ohio	United States	45840
226	Blanchard Valley Hospital	Findlay	Ohio	United States	45840
227	Orion Cancer Care	Findlay	Ohio	United States	45840
228	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
229	Dayton Physicians LLC-Atrium	Franklin	Ohio	United States	45005
230	Dayton Physicians LLC-Wayne	Greenville	Ohio	United States	45331
231	Wayne Hospital	Greenville	Ohio	United States	45331
232	Greater Dayton Cancer Center	Kettering	Ohio	United States	45409
233	Kettering Medical Center	Kettering	Ohio	United States	45429
234	Fairfield Medical Center	Lancaster	Ohio	United States	43130
235	Marietta Memorial Hospital	Marietta	Ohio	United States	45750
236	OhioHealth Marion General Hospital	Marion	Ohio	United States	43302
237	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio	United States	44124
238	UH Seidman Cancer Center at Landerbrook Health Center	Mayfield Heights	Ohio	United States	44124
239	UH Seidman Cancer Center at Lake Health Mentor Campus	Mentor	Ohio	United States	44060
240	Dayton Physicians LLC-Signal Point	Middletown	Ohio	United States	45042
241	Knox Community Hospital	Mount Vernon	Ohio	United States	43050
242	Licking Memorial Hospital	Newark	Ohio	United States	43055
243	Newark Radiation Oncology	Newark	Ohio	United States	43055
244	Southern Ohio Medical Center	Portsmouth	Ohio	United States	45662
245	Dayton Physicians LLC-Wilson	Sidney	Ohio	United States	45365
246	Springfield Regional Cancer Center	Springfield	Ohio	United States	45504
247	Springfield Regional Medical Center	Springfield	Ohio	United States	45505
248	Dayton Physicians LLC-Upper Valley	Troy	Ohio	United States	45373
249	Upper Valley Medical Center	Troy	Ohio	United States	45373
250	University Hospitals Sharon Health Center	Wadsworth	Ohio	United States	44281
251	Saint Ann's Hospital	Westerville	Ohio	United States	43081
252	UHHS-Westlake Medical Center	Westlake	Ohio	United States	44145
253	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio	United States	43701
254	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
255	Oklahoma Cancer Specialists and Research Institute-Tulsa	Tulsa	Oklahoma	United States	74146
256	Saint Charles Health System	Bend	Oregon	United States	97701
257	Clackamas Radiation Oncology Center	Clackamas	Oregon	United States	97015
258	Providence Cancer Institute Clackamas Clinic	Clackamas	Oregon	United States	97015
259	Bay Area Hospital	Coos Bay	Oregon	United States	97420
260	Providence Newberg Medical Center	Newberg	Oregon	United States	97132
261	Providence Willamette Falls Medical Center	Oregon City	Oregon	United States	97045
262	Providence Portland Medical Center	Portland	Oregon	United States	97213
263	Providence Saint Vincent Medical Center	Portland	Oregon	United States	97225
264	Jefferson Abington Hospital	Abington	Pennsylvania	United States	19001
265	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania	United States	18103
266	Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania	United States	18017
267	Christiana Care Health System-Concord Health Center	Chadds Ford	Pennsylvania	United States	19317
268	Ephrata Cancer Center	Ephrata	Pennsylvania	United States	17522
269	Adams Cancer Center	Gettysburg	Pennsylvania	United States	17325
270	Cherry Tree Cancer Center	Hanover	Pennsylvania	United States	17331
271	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania	United States	19104
272	Reading Hospital	West Reading	Pennsylvania	United States	19611
273	WellSpan Health-York Cancer Center	York	Pennsylvania	United States	17403
274	WellSpan Health-York Hospital	York	Pennsylvania	United States	17403
275	Women and Infants Hospital	Providence	Rhode Island	United States	02905
276	Prisma Health Cancer Institute - Spartanburg	Boiling Springs	South Carolina	United States	29316
277	Medical University of South Carolina	Charleston	South Carolina	United States	29425
278	Prisma Health Cancer Institute - Easley	Easley	South Carolina	United States	29640
279	Greenville Health System Cancer Institute-Andrews	Greenville	South Carolina	United States	29601
280	Saint Francis Hospital	Greenville	South Carolina	United States	29601
281	Prisma Health Cancer Institute - Butternut	Greenville	South Carolina	United States	29605
282	Prisma Health Cancer Institute - Faris	Greenville	South Carolina	United States	29605
283	Prisma Health Greenville Memorial Hospital	Greenville	South Carolina	United States	29605
284	Saint Francis Cancer Center	Greenville	South Carolina	United States	29607
285	Prisma Health Cancer Institute - Eastside	Greenville	South Carolina	United States	29615
286	Prisma Health Cancer Institute - Greer	Greer	South Carolina	United States	29650
287	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina	United States	29672
288	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
289	Memorial Hospital	Chattanooga	Tennessee	United States	37404
290	Pulmonary Medicine Center of Chattanooga-Hixson	Hixson	Tennessee	United States	37343
291	Memorial GYN Plus	Ooltewah	Tennessee	United States	37363
292	M D Anderson Cancer Center	Houston	Texas	United States	77030
293	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah	United States	84112
294	South Jordan Health Center	South Jordan	Utah	United States	84009
295	Inova Fairfax Hospital	Falls Church	Virginia	United States	22042
296	Providence Regional Cancer System-Aberdeen	Aberdeen	Washington	United States	98520
297	Cancer Care Center at Island Hospital	Anacortes	Washington	United States	98221
298	Swedish Cancer Institute-Eastside Oncology Hematology	Bellevue	Washington	United States	98005
299	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington	United States	98225
300	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington	United States	98310
301	Harrison Medical Center	Bremerton	Washington	United States	98310
302	Highline Medical Center-Main Campus	Burien	Washington	United States	98166
303	Providence Regional Cancer System-Centralia	Centralia	Washington	United States	98531
304	Swedish Cancer Institute-Edmonds	Edmonds	Washington	United States	98026
305	Saint Elizabeth Hospital	Enumclaw	Washington	United States	98022
306	Providence Regional Cancer Partnership	Everett	Washington	United States	98201
307	Saint Francis Hospital	Federal Way	Washington	United States	98003
308	Swedish Cancer Institute-Issaquah	Issaquah	Washington	United States	98029
309	Providence Regional Cancer System-Lacey	Lacey	Washington	United States	98503
310	Saint Clare Hospital	Lakewood	Washington	United States	98499
311	PeaceHealth Saint John Medical Center	Longview	Washington	United States	98632
312	Harrison HealthPartners Hematology and Oncology-Poulsbo	Poulsbo	Washington	United States	98370
313	Minor and James Medical PLLC	Seattle	Washington	United States	98104
314	Pacific Gynecology Specialists	Seattle	Washington	United States	98104
315	Swedish Medical Center-Ballard Campus	Seattle	Washington	United States	98107
316	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
317	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
318	Kaiser Permanente Washington	Seattle	Washington	United States	98112
319	Swedish Medical Center-First Hill	Seattle	Washington	United States	98122-4307
320	University of Washington Medical Center - Northwest	Seattle	Washington	United States	98133
321	Women's Cancer Center of Seattle	Seattle	Washington	United States	98133
322	University of Washington Medical Center - Montlake	Seattle	Washington	United States	98195
323	Providence Regional Cancer System-Shelton	Shelton	Washington	United States	98584
324	MultiCare Deaconess Cancer and Blood Specialty Center - Valley	Spokane Valley	Washington	United States	99216
325	MultiCare Deaconess Cancer and Blood Specialty Center - Downtown	Spokane	Washington	United States	99204
326	Evergreen Hematology and Oncology PS	Spokane	Washington	United States	99218
327	Franciscan Research Center-Northwest Medical Plaza	Tacoma	Washington	United States	98405
328	Northwest Medical Specialties PLLC	Tacoma	Washington	United States	98405
329	PeaceHealth Southwest Medical Center	Vancouver	Washington	United States	98664
330	Providence Saint Mary Regional Cancer Center	Walla Walla	Washington	United States	99362
331	North Star Lodge Cancer Center at Yakima Valley Memorial Hospital	Yakima	Washington	United States	98902
332	Providence Regional Cancer System-Yelm	Yelm	Washington	United States	98597
333	Monongalia Hospital	Morgantown	West Virginia	United States	26505
334	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
335	Big Horn Basin Cancer Center	Cody	Wyoming	United States	82414
336	Billings Clinic-Cody	Cody	Wyoming	United States	82414
337	Welch Cancer Center	Sheridan	Wyoming	United States	82801

Sponsors and Collaborators

• National Cancer Institute (NCI)
• NRG Oncology

Investigators

• Principal Investigator: Alessandro D Santin, NRG Oncology

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 31, 2017

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT02257528
• Other Study ID Numbers: NCI-2014-02021; NCI-2014-02021; PNRG-GY002_A01PAMDREVW01; NRG-GY002; NRG-GY002; NRG-GY002; U10CA180868
• First Posted: Oct 6, 2014
• Last Update Posted: Jul 28, 2022
• Last Verified: Jan 1, 2022

• Additional relevant MeSH terms: Carcinoma; Uterine Cervical Neoplasms; Carcinoma, Adenosquamous; Recurrence; Nivolumab

Study Results

Participant Flow

Recruitment Details	This study was activated on 5/18/2015 and closed to accrual on 6/8/2016.

Arm/Group Title	Treatment (Nivolumab)
Arm/Group Description	Patients were treated with 4 doses of IV nivolumab (3 mg/kg every 2 weeks), followed by an additional 42 doses 3 mg/kg every 2 weeks for a maximum of 46 doses until disease progression or adverse effects prohibit therapy.
Period Title: Overall Study
STARTED	26
COMPLETED	25
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Treatment (Nivolumab)
Arm/Group Description	Patients were treated with 4 doses of IV nivolumab (3 mg/kg every 2 weeks), followed by an additional 42 doses 3 mg/kg every 2 weeks for a maximum of 46 doses until disease progression or adverse effects prohibit therapy.
Overall Participants	25
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46.6 (11.6)
Age, Customized (Count of Participants)
20-29 years	1 4%
30-39 years	7 28%
40-49 years	8 32%
50-59 years	5 20%
60-69 years	3 12%
70-79 years	1 4%
Sex: Female, Male (Count of Participants)
Female	25 100%
Male	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 8%
Not Hispanic or Latino	22 88%
Unknown or Not Reported	1 4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	5 20%
White	18 72%
More than one race	0 0%
Unknown or Not Reported	2 8%

Outcome Measures

1. Primary Outcome

Title	Objective Tumor Response as Assessed by RECIST 1.1 Criteria
Description	Proportion of participants with objective tumor response. Objective tumor response is defined as complete or partial tumor response assessed by RECIST 1.1.
Time Frame	The average of study treatment time was 3.8 months.

Outcome Measure Data

Analysis Population Description

Eligible and evaluable participants

Arm/Group Title	Treatment (Nivolumab)
Arm/Group Description	Patients were treated with 4 doses of IV nivolumab (3 mg/kg every 2 weeks), followed by an additional 42 doses 3 mg/kg every 2 weeks for a maximum of 46 doses until disease progression or adverse effects prohibit therapy.
Measure Participants	25
Number (90% Confidence Interval) [percentage of participants]	4 16%

2. Primary Outcome

Title	Adverse Events (Grade 3 or Higher) During Treatment Period as Assessed by CTCAE Version 4
Description	Number of participants with a maximum grade of 3 or higher during treatment period. Adverse events are graded and categorized using CTCAE v4.0.
Time Frame	Within 100 days of last protocol treatment

Outcome Measure Data

Analysis Population Description

Eligible and evaluable patients

Arm/Group Title	Treatment (Nivolumab)
Arm/Group Description	Patients were treated with 4 doses of IV nivolumab (3 mg/kg every 2 weeks), followed by an additional 42 doses 3 mg/kg every 2 weeks for a maximum of 46 doses until disease progression or adverse effects prohibit therapy.
Measure Participants	25
Leukopenia	1 4%
Thrombocytopenia	1 4%
Neutropenia	1 4%
Anemia	3 12%
Other Investigations	4 16%
Endocrine Disorders	1 4%
Gastrointestinal disorders	5 20%
General disorders & administration site conditions	1 4%
Hepatobiliary disorders	1 4%
Infections and Infestations	1 4%
Metabolism and nutrition disorders	5 20%
Musculoskeletal and connective tissue disorders	1 4%
Neoplasms benign, malignant and unspecified	2 8%
Other nervous system disorders	1 4%
Reproductive system and breast disorders	1 4%
Vascular disorders	1 4%

3. Secondary Outcome

Title	Progression-free Survival
Description	Progression-free survival is the period of time from study entry to time of disease progression, death or date of last contact, whichever occurs first. Progression is assessed by RECIST 1.1.
Time Frame	Time from study entry to time of progression or death, whichever occurs first, up to 5 years of follow-up.

Outcome Measure Data

Analysis Population Description

Eligible and Evaluable patients

Arm/Group Title	Treatment (Nivolumab)
Arm/Group Description	Patients were treated with 4 doses of IV nivolumab (3 mg/kg every 2 weeks), followed by an additional 42 doses 3 mg/kg every 2 weeks for a maximum of 46 doses until disease progression or adverse effects prohibit therapy.
Measure Participants	25
Median (90% Confidence Interval) [months]	3.5

4. Secondary Outcome

Title	Overall Survival
Description	Overall survival is defined as the duration of time from study entry to time of death or the date of last contact.
Time Frame	Time from study entry to time of death or the date of last contact, up to 5 years of follow-up

Outcome Measure Data

Analysis Population Description

Eligible and evaluable patients

Arm/Group Title	Treatment (Nivolumab)
Arm/Group Description	Patients were treated with 4 doses of IV nivolumab (3 mg/kg every 2 weeks), followed by an additional 42 doses 3 mg/kg every 2 weeks for a maximum of 46 doses until disease progression or adverse effects prohibit therapy.
Measure Participants	25
Median (90% Confidence Interval) [months]	14.5

5. Other Pre-specified Outcome

Title	Tumor Expressions of PD-1 and PD-L1 in Tumor Infiltrating Lymphocytes and Cervical Cancer Cells
Description	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.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Other Pre-specified Outcome

Title	Immune Infiltration Related Biomarkers (i.e., CD4+, CD8+, FoxP3) in Tumor Specimens
Description	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.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Other Pre-specified Outcome

Title	Change in the Immune Response to HPV 16/18/31/35/45 E7 Antigen in Peripheral Blood Lymphocytes and Serum
Description	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.
Time Frame	Baseline to up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Other Pre-specified Outcome

Title	Change in the CTC Count
Description	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.
Time Frame	Baseline to up to 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	All Adverse Events (AEs) occurring during treatment and up to 5 years after are reported.
Arm/Group Title	Treatment (Nivolumab)
Arm/Group Description	Patients were treated with 4 doses of IV nivolumab (3 mg/kg every 2 weeks), followed by an additional 42 doses 3 mg/kg every 2 weeks for a maximum of 46 doses until disease progression or adverse effects prohibit therapy.
All Cause Mortality
	Treatment (Nivolumab)
	Affected / at Risk (%)	# Events
Total	19/25 (76%)
Serious Adverse Events
	Treatment (Nivolumab)
	Affected / at Risk (%)	# Events
Total	12/25 (48%)
Endocrine disorders
Hypothyroidism	1/25 (4%)
Gastrointestinal disorders
Colonic Obstruction	1/25 (4%)
Colitis	1/25 (4%)
Abdominal Pain	2/25 (8%)
Hepatobiliary disorders
Bile Duct Stenosis	1/25 (4%)
Infections and infestations
Kidney Infection	1/25 (4%)
Investigations
Serum Amylase Increased	1/25 (4%)
Alanine Aminotransferase Increased	1/25 (4%)
Metabolism and nutrition disorders
Dehydration	1/25 (4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor Pain	2/25 (8%)
Reproductive system and breast disorders
Vaginal Hemorrhage	1/25 (4%)
Pelvic Pain	1/25 (4%)
Vascular disorders
Thromboembolic Event	1/25 (4%)
Other (Not Including Serious) Adverse Events
	Treatment (Nivolumab)
	Affected / at Risk (%)	# Events
Total	24/25 (96%)
Blood and lymphatic system disorders
Blood And Lymphatic System Disorders - Other	2/25 (8%)
Anemia	14/25 (56%)
Cardiac disorders
Palpitations	1/25 (4%)
Sinus Tachycardia	1/25 (4%)
Ear and labyrinth disorders
Tinnitus	1/25 (4%)
Endocrine disorders
Hypothyroidism	5/25 (20%)
Hyperthyroidism	2/25 (8%)
Endocrine Disorders - Other	1/25 (4%)
Eye disorders
Conjunctivitis	1/25 (4%)
Gastrointestinal disorders
Dysphagia	1/25 (4%)
Colonic Obstruction	2/25 (8%)
Colitis	1/25 (4%)
Constipation	8/25 (32%)
Diarrhea	6/25 (24%)
Vomiting	9/25 (36%)
Bloating	1/25 (4%)
Stomach Pain	1/25 (4%)
Abdominal Pain	11/25 (44%)
Abdominal Distension	1/25 (4%)
Nausea	12/25 (48%)
Gastroesophageal Reflux Disease	1/25 (4%)
Rectal Pain	1/25 (4%)
Ascites	1/25 (4%)
Flatulence	4/25 (16%)
General disorders
Pain	2/25 (8%)
Flu Like Symptoms	1/25 (4%)
Edema Limbs	8/25 (32%)
Fatigue	15/25 (60%)
Fever	5/25 (20%)
Chills	2/25 (8%)
Infusion Related Reaction	1/25 (4%)
Hepatobiliary disorders
Bile Duct Stenosis	1/25 (4%)
Infections and infestations
Upper Respiratory Infection	2/25 (8%)
Vulval Infection	1/25 (4%)
Lung Infection	1/25 (4%)
Kidney Infection	1/25 (4%)
Vaginal Infection	1/25 (4%)
Urinary Tract Infection	3/25 (12%)
Injury, poisoning and procedural complications
Fracture	1/25 (4%)
Fall	1/25 (4%)
Bruising	2/25 (8%)
Investigations
Investigations - Other	3/25 (12%)
Weight Loss	5/25 (20%)
Serum Amylase Increased	2/25 (8%)
Platelet Count Decreased	3/25 (12%)
Lymphocyte Count Decreased	3/25 (12%)
Lipase Increased	1/25 (4%)
Creatinine Increased	6/25 (24%)
Neutrophil Count Decreased	2/25 (8%)
Blood Bilirubin Increased	2/25 (8%)
White Blood Cell Decreased	4/25 (16%)
Aspartate Aminotransferase Increased	4/25 (16%)
Alkaline Phosphatase Increased	5/25 (20%)
Alanine Aminotransferase Increased	5/25 (20%)
Metabolism and nutrition disorders
Hyponatremia	2/25 (8%)
Hypomagnesemia	4/25 (16%)
Hypokalemia	5/25 (20%)
Hypocalcemia	2/25 (8%)
Hypoalbuminemia	4/25 (16%)
Hyperglycemia	8/25 (32%)
Hypercalcemia	1/25 (4%)
Dehydration	2/25 (8%)
Anorexia	7/25 (28%)
Musculoskeletal and connective tissue disorders
Pain In Extremity	5/25 (20%)
Neck Pain	1/25 (4%)
Myalgia	3/25 (12%)
Flank Pain	5/25 (20%)
Back Pain	6/25 (24%)
Arthritis	1/25 (4%)
Arthralgia	4/25 (16%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor Pain	1/25 (4%)
Nervous system disorders
Seizure	1/25 (4%)
Recurrent Laryngeal Nerve Palsy	1/25 (4%)
Peripheral Sensory Neuropathy	6/25 (24%)
Headache	7/25 (28%)
Dizziness	2/25 (8%)
Akathisia	1/25 (4%)
Psychiatric disorders
Insomnia	3/25 (12%)
Depression	2/25 (8%)
Anxiety	3/25 (12%)
Renal and urinary disorders
Urinary Urgency	2/25 (8%)
Urinary Incontinence	1/25 (4%)
Urinary Tract Pain	1/25 (4%)
Urinary Frequency	1/25 (4%)
Urinary Fistula	1/25 (4%)
Proteinuria	2/25 (8%)
Hematuria	1/25 (4%)
Cystitis Noninfective	1/25 (4%)
Reproductive system and breast disorders
Vaginal Pain	2/25 (8%)
Vaginal Hemorrhage	3/25 (12%)
Vaginal Fistula	1/25 (4%)
Pelvic Pain	3/25 (12%)
Irregular Menstruation	1/25 (4%)
Vaginal Discharge	1/25 (4%)
Respiratory, thoracic and mediastinal disorders
Pleural Effusion	1/25 (4%)
Nasal Congestion	2/25 (8%)
Hoarseness	1/25 (4%)
Dyspnea	2/25 (8%)
Cough	6/25 (24%)
Wheezing	1/25 (4%)
Allergic Rhinitis	2/25 (8%)
Skin and subcutaneous tissue disorders
Skin And Subcutaneous Tissue Disorders - Other	1/25 (4%)
Pruritus	1/25 (4%)
Rash Maculo-Papular	3/25 (12%)
Nail Loss	1/25 (4%)
Hyperhidrosis	1/25 (4%)
Vascular disorders
Thromboembolic Event	3/25 (12%)
Hypotension	1/25 (4%)
Hypertension	7/25 (28%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.