NCT02257528|Active Not RecruitingPhase 2Results

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

A Phase II Evaluation of Nivolumab, a Fully Human Antibody Against PD-1, in the Treatment of Persistent or Recurrent Cervical Cancer

National Cancer Institute (NCI)ClinicalTrials.gov

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4 other identifiers

NCI-2014-02021PNRG-GY002_A01PAMDREVW01NRG-GY002U10CA180868

Study Type

interventional

Target

Locations

1 country

Sites

333

Timeline

RegisteredOct 2014

StartedMay 2015

CompletionMar 2027

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.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

participants targeted

Target at below P25 for phase_2

Timeline

10mo left

Started May 2015

Longer than P75 for phase_2

Geographic Reach

1 country

333 active sites

Status

active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

11.9 years study duration

Study Progress92%

May 2015Mar 2027

First Submitted

Initial submission to the registry

October 2, 2014

Completed

4 days until next milestone

First Posted

Study publicly available on registry

October 6, 2014

Completed

7 months until next milestone

Study Start

First participant enrolled

May 18, 2015

Completed

3.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 5, 2019

Completed

1.4 years until next milestone

Results Posted

Study results publicly available

August 12, 2020

Completed

6.6 years until next milestone

Study Completion

Last participant's last visit for all outcomes

March 30, 2027

Expected

Last Updated

April 29, 2026

Status Verified

March 1, 2026

Enrollment Period

3.8 years

First QC Date

October 2, 2014

Results QC Date

May 11, 2020

Last Update Submit

April 9, 2026

Conditions

Cervical Adenocarcinoma Recurrent Cervical Carcinoma Stage IVB Cervical Cancer AJCC v6 and v7 Cervical Adenosquamous Carcinoma Stage IV Cervical Cancer AJCC v6 and v7 Stage IVA Cervical Cancer AJCC v6 and v7

Outcome Measures

Primary Outcomes (2)

Objective Tumor Response as Assessed by RECIST 1.1 Criteria
Proportion of participants with objective tumor response. Objective tumor response is defined as complete or partial tumor response assessed by RECIST 1.1.
The average of study treatment time was 3.8 months.
Adverse Events (Grade 3 or Higher) During Treatment Period as Assessed by CTCAE Version 4
Number of participants with a maximum grade of 3 or higher during treatment period. Adverse events are graded and categorized using CTCAE v4.0.
Within 100 days of last protocol treatment

Secondary Outcomes (2)

Progression-free Survival
Time from study entry to time of progression or death, whichever occurs first, up to 5 years of follow-up.
Overall Survival
Time from study entry to time of death or the date of last contact, up to 5 years of follow-up

Other Outcomes (4)

Tumor Expressions of PD-1 and PD-L1 in Tumor Infiltrating Lymphocytes and Cervical Cancer Cells
Up to 5 years
Immune Infiltration Related Biomarkers (i.e., CD4+, CD8+, FoxP3) in Tumor Specimens
Up to 5 years
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
+1 more other outcomes

Study Arms (1)

Treatment (nivolumab)

EXPERIMENTAL

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 AnalysisBiological: Nivolumab

Interventions

Laboratory Biomarker AnalysisOTHER

Correlative studies

Treatment (nivolumab)

NivolumabBIOLOGICAL

Given IV

Also known as: ABP 206, BCD-263, BMS 936558, BMS-936558, BMS936558, CMAB819, MDX 1106, MDX-1106, MDX1106, NIVO, Nivolumab Biosimilar ABP 206, Nivolumab Biosimilar BCD-263, Nivolumab Biosimilar CMAB819, ONO 4538, ONO-4538, ONO4538, Opdivo

Treatment (nivolumab)

Eligibility Criteria

Age18 Years+

Sexfemale

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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
+6 more criteria

You may not qualify if:

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
+3 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

National Cancer Institute (NCI)lead
NRG Oncologycollaborator

Study Sites (333)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, 35233, United States

Location

Anchorage Associates in Radiation Medicine

Anchorage, Alaska, 98508, United States

Location

Anchorage Radiation Therapy Center

Anchorage, Alaska, 99504, United States

Location

Alaska Breast Care and Surgery LLC