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Nivolumab in Treating Patients With Refractory Metastatic Anal Canal Cancer

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ClinicalTrials.gov Identifier: NCT02314169
Recruitment Status : Recruiting
First Posted : December 11, 2014
Last Update Posted : September 11, 2018
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

December 10, 2014
December 11, 2014
September 11, 2018
May 1, 2015
January 31, 2020   (Final data collection date for primary outcome measure)
Overall Response Rate: Number of Participants With Response [ Time Frame: Up to 2 years ]
Responses assessed using computed tomography (CT) scans or magnetic resonance imaging according to standard Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria in order to assess disease progression. Complete Response (CR): Disappearance all target lesions; any pathological lymph nodes reduction in short axis to < 10 mm (< 1 cm). Partial Response (PR): > 30% decrease in sum diameters of target lesions. Progressive Disease (PD): > 20% increase in sum diameters lesions. (Note: appearance of one or > new lesions considered progressions). Stable Disease (SD): Neither shrinkage qualify for PR nor increase for PD.
Overall response rate [ Time Frame: Up to 2 years ]
Responses will be assessed using CT scans or magnetic resonance imaging according to standard RECIST 1.1 criteria in order to assess disease progression.
Complete list of historical versions of study NCT02314169 on ClinicalTrials.gov Archive Site
  • Number of Participants With Toxicities Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 [ Time Frame: Up to 100 days post-treatment ]
    The most frequent of adverse events measured relative to the total number of patients treated, and the toxicities tabulated by grade according to CTCAE.
  • Overall Survival [ Time Frame: From initiation of treatment with nivolumab until death, assessed up to 2 years ]
    Time measured from initiation of treatment with nivolumab till death. Kaplan-Meier analysis will be performed to estimate the median overall survival with a 95% confidence interval.
  • Progression-free Survival [ Time Frame: From initiation of treatment with nivolumab until the time of disease progression, assessed up to 2 years ]
    From initiation of treatment with nivolumab until the time of disease progression, time measured in months. Kaplan-Meier analysis performed to estimate the median progression-free survival with a 90% confidence interval.
  • Progression-free Survival [ Time Frame: From initiation of treatment with nivolumab until the time of disease progression according to RECIST version 1.1 criteria, assessed up to 2 years ]
    Kaplan-Meier analysis will be performed to estimate the median progression-free survival with a 90% confidence interval.
  • Overall Survival [ Time Frame: From initiation of treatment with nivolumab until death, assessed up to 2 years ]
    Kaplan-Meier analysis will be performed to estimate the median overall survival with a 90% confidence interval.
  • Incidence of toxicities graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 100 days post-treatment ]
    The frequency of each serious adverse event will be measured relative to the total number or patients treated. Toxicities will be tabulated by type and grade.
Expression of Biomarkers Using Immunohistochemistry and Blood Samples [ Time Frame: Up to time of treatment discontinuation ]
Descriptive statistics including plots, mean, median and standard deviations will be used to summarize data. For continuous outcomes, t-test and analysis of variance will be used to compare outcome measures across patient characteristics. Pair-wise comparisons will be performed using pre- and post-therapy samples from each patient. The chi-square test or Fisher's exact test will be used to test the association between two categorical variables. Both univariate and multivariate logistic regressions will be performed to model prognostic factors.
  • Expression of Biomarkers Using Immunohistochemistry and Blood Samples [ Time Frame: Up to time of treatment discontinuation ]
    Descriptive statistics including plots, mean, median and standard deviations will be used to summarize data. For continuous outcomes, t-test and analysis of variance will be used to compare outcome measures across patient characteristics. Pair-wise comparisons will be performed using pre- and post-therapy samples from each patient. The chi-square test or Fisher's exact test will be used to test the association between two categorical variables. Both univariate and multivariate logistic regressions will be performed to model prognostic factors.
  • Responses assessed using the IRRC [ Time Frame: Up to 2 years ]
    IRRC response will be correlated with ORR, PFS, and OS. ORR according to IRRC will be calculated according to the number of IRRC responses relative to the number of patients with metastatic SCCA of the anal canal treated with nivolumab and assessed for response according to these criteria. Kaplan-Meier analyses will be performed to estimate median PFS and OS.
 
Nivolumab in Treating Patients With Refractory Metastatic Anal Canal Cancer
A Multi-Institutional Phase 2 Study of Nivolumab in Refractory Metastatic Squamous Cell Carcinoma of the Anal Canal
This phase II trial studies how well nivolumab works in treating patients with anal canal cancer that has not responded to previous treatment (refractory) and has spread to other places in the body (metastatic). Monoclonal antibodies, such as nivolumab, may block tumor growth in different ways by targeting certain cells.

PRIMARY OBJECTIVES:

I. To evaluate overall response rate (ORR) with nivolumab in patients with previously treated metastatic squamous cell carcinoma (SCCA) of the anal canal.

SECONDARY OBJECTIVES:

I. To evaluate progression-free survival (PFS) of nivolumab in patients with previously treated metastatic SCCA of the anal canal.

II. To evaluate overall survival (OS) in patients with previously treated metastatic SCCA of the anal canal treated with nivolumab.

III. To evaluate the grade 3 and 4 toxicity rate in patients with previously treated metastatic SCCA of the anal canal when treated with nivolumab.

TERTIARY OBJECTIVES:

I. To evaluate ORR, PFS, and OS based on expression of programmed cell death 1 ligand 1 (PD-L1), programmed cell death 1 (PD-1), peritumoral cluster of differentiation (CD)8+ tumor infiltrating lymphocytes (TILs), peritumoral CD4+ TILs, and regulatory T cells as analyzed from tumor biopsies in previously treated patients with metastatic SCCA of the anal canal when treated with nivolumab.

II. To evaluate radiographic responses according to relative changes in proportions of anti-human papillomavirus (HPV) specific CD8+ and CD4+ TILs and regulatory T cells in patients with previously treated metastatic SCCA of the anal canal following treatment with nivolumab, analyzed from serial peripheral blood samples.

OUTLINE:

Patients receive nivolumab intravenously (IV) over approximately 60 minutes once every two weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 100 days and then every 3 months for 2 years.

Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Anal Canal Squamous Cell Carcinoma
  • Metastatic Anal Canal Carcinoma
  • Recurrent Anal Canal Carcinoma
  • Stage IV Anal Canal Cancer AJCC v6 and v7
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Biological: Nivolumab
    Given IV
    Other Names:
    • BMS-936558
    • MDX-1106
    • NIVO
    • ONO-4538
    • Opdivo
Experimental: Treatment (nivolumab)
Patients receive nivolumab IV over approximately 60 minutes once every two weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.
Interventions:
  • Other: Laboratory Biomarker Analysis
  • Biological: Nivolumab
Morris VK, Salem ME, Nimeiri H, Iqbal S, Singh P, Ciombor K, Polite B, Deming D, Chan E, Wade JL, Xiao L, Bekaii-Saab T, Vence L, Blando J, Mahvash A, Foo WC, Ohaji C, Pasia M, Bland G, Ohinata A, Rogers J, Mehdizadeh A, Banks K, Lanman R, Wolff RA, Streicher H, Allison J, Sharma P, Eng C. Nivolumab for previously treated unresectable metastatic anal cancer (NCI9673): a multicentre, single-arm, phase 2 study. Lancet Oncol. 2017 Apr;18(4):446-453. doi: 10.1016/S1470-2045(17)30104-3. Epub 2017 Feb 18.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
37
Same as current
January 31, 2020
January 31, 2020   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed previously treated metastatic squamous cell carcinoma of the anal canal
  • Patients must have measurable disease according to the standard Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, computed tomography (CT) scans or magnetic resonance imagings (MRIs) used to assess the measurable disease must have been completed within 28 days prior to study drug initiation
  • Patients must have been treated with at least one prior systemic treatment for incurable advanced or metastatic SCCA of the anal canal; prior treatment for metastatic disease is not required for patients who develop new metastatic lesions during or within 6 months of completion of chemoradiation for limited-stage disease; patients who receive chemotherapy for incurable advanced or metastatic SCCA of the anal canal must wait a minimum >= 28 days (6 weeks for nitrosoureas or mitomycin C) after the date of completion of chemotherapy prior to initiating treatment with nivolumab on this study; patients who undergo radiotherapy to a site of tumor must wait a minimum >= 3 months from the date of completion of radiotherapy prior to initiating treatment with nivolumab on this study
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (Karnofsky >= 80%)
  • Leukocytes >= 2,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Hemoglobin >= 9.0 gm/dL
  • Platelets >= 100,000/mcL
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (except patients with Gilbert syndrome, who can have total bilirubin < 3.0 mg/dL)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN
  • Serum creatinine =< 1.5 x ULN OR creatinine clearance (CrCl) >= 50 mL/min (if using the Cockcroft-Gault formula)
  • Women of child-bearing potential (WOCBP) and men 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; women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/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 as well as azoospermic men) 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 or bilateral oophorectomy) or who is not postmenopausal; menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes
  • WOCBP receiving nivolumab will be instructed to adhere to contraception for a period of 23 weeks after the last dose of investigational product; men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product
  • Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she (or the participating partner) should inform the treating physician immediately
  • Ability to understand and the willingness to sign a written informed consent document
  • Brain metastases are allowed if they have been adequately treated with radiotherapy or surgery and have been stable for at least three months prior to registration; eligible subjects should be neurologically asymptomatic; there is no magnetic resonance imaging (MRI) evidence of progression for a minimum of 4 weeks 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
  • All patients must be willing to undergo testing for human immunodeficiency virus (HIV) testing if not tested within the past 6 months
  • If HIV+ positive, all patients infected with human immunodeficiency virus (HIV) may be eligible for study provided that their CD4+ count >= 300/uL; their viral load is undetectable; they are currently receiving highly active antiretroviral therapy (HAART)
  • All HIV+ patients will be under the care of an infectious diseases specialist; if a relationship with an infectious diseases specialist is not established, infectious disease specialist will be consulted; records of all viral counts and peripheral T-cell counts must be sent to the study coordinator in order to follow these values over the course of treatment
  • All patients must be willing to be tested for hepatitis screening; patients co-infected with hepatitis B virus and/or hepatitis C virus may be included in this study provided that their liver function tests remain within the limits listed above; patients must be followed by a hepatologist during the course of this study

Exclusion Criteria:

  • Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events (AEs) due to agents administered more than 4 weeks earlier (i.e., grade >= 2 AE present); palliative (limited-field) radiation therapy is permitted, as long as the lesion being considered for palliative radiation is not a target lesion
  • Patients who are receiving any other investigational agents
  • Patients should be excluded if they have had prior treatment with an anti-PD-1, anti-PD-L1, anti-programmed cell death ligand 2 (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 checkpoint pathways
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab
  • History of severe hypersensitivity reaction to any monoclonal antibody
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • 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 chronic prolonged systemic corticosteroids (defined as corticosteroid use of duration one month or greater), 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 (IBD), Crohn's, ulcerative colitis, and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or anti-phospholipid syndrome should be excluded
  • 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
  • No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for at least three years
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
No
Canada,   United States
 
 
NCT02314169
NCI-2014-02420
NCI-2014-02420 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
NCI9673
P9673_R03PAPPHOLD01
9673 ( Other Identifier: University of Texas MD Anderson Cancer Center LAO )
9673 ( Other Identifier: CTEP )
N01CM00032 ( U.S. NIH Grant/Contract )
N01CM00038 ( U.S. NIH Grant/Contract )
N01CM00039 ( U.S. NIH Grant/Contract )
N01CM00071 ( U.S. NIH Grant/Contract )
N01CM00099 ( U.S. NIH Grant/Contract )
N01CM00100 ( U.S. NIH Grant/Contract )
P30CA016672 ( U.S. NIH Grant/Contract )
UM1CA186704 ( U.S. NIH Grant/Contract )
UM1CA186712 ( U.S. NIH Grant/Contract )
UM1CA186716 ( U.S. NIH Grant/Contract )
No
Not Provided
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Cathy Eng University of Texas MD Anderson Cancer Center LAO
National Cancer Institute (NCI)
August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP