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Nasopharyngeal Nonkeratinizing CarcinomaPhase 2NCT02339558

Nivolumab in Treating Patients With Recurrent and/or Metastatic Nasopharyngeal Cancer

A Phase 2 study testing Laboratory Biomarker Analysis and Nivolumab in people with Nasopharyngeal Nonkeratinizing Carcinoma and Recurrent Nasopharynx Carcinoma, run by National Cancer Institute (NCI) at 19 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This phase II trial studies how well nivolumab works in treating patients with nasopharyngeal cancer that has returned after a period of improvement (recurrent) and/or has spread to other parts of the body (metastatic). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Laboratory Biomarker Analysis and Nivolumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
45 participants
Where
19 sitesin 3 countries
Study dates
21 Jul 2015to 16 Jun 2018
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Ability to understand and the willingness to sign a written informed consent document
  • Histologically or cytologically confirmed non-keratinizing nasopharyngeal carcinoma (NPC) that has recurred at locoregional and/or distant sites; NOTE: patients with local recurrence at the bony skull-base as the only site of index disease are excluded; patients with locoregional recurrence without distant metastases must have undergone radical radiotherapy previously
  • Measurable disease according to the RECIST criteria (version 1.1), for the evaluation of measurable disease
  • Received one or more lines of chemotherapy, which must include prior treatment with a platinum agent and must not be amenable to potentially curative radiotherapy or surgery
  • Archived or fresh tumor sample available; willingness to donate blood and tissue for mandatory correlative research studies
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
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  • Absolute neutrophil count >= 1.5 x 10^9/L
  • Platelet count >= 100 x 10^9/L
  • Hemoglobin >= 8.0 g/dL
  • Serum alanine aminotransferase ([ALT]; serum glutamate-pyruvate transferase [SGPT]), or serum aspartate aminotransferase [AST] where available at the center) < 2.5 x upper limit of normal (ULN), OR < 5 x ULN in the presence of liver metastases
  • Serum total bilirubin < 2 x ULN (except patients with Gilbert syndrome, who can have total bilirubin < 3.0 mg/dL)
  • Serum creatinine < 1.5 x ULN

Who cannot join

  • Any of the following:
  • Chemotherapy =< 4 weeks prior to registration
  • Radiotherapy =< 4 weeks prior to registration
  • Nitrosoureas =< 6 weeks prior to registration or
  • Mitomycin C =< 6 weeks prior to registration
  • Those who have not recovered from adverse events (to grade =< 1 in severity) due to agents administered more than 4 weeks earlier; prior palliative radiotherapy to bone metastases =< 2 weeks prior to registration (i.e. prior palliative radiotherapy to bone metastases is allowed if it is performed > 2 weeks prior to registration)
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  • Prior investigational agents =< 4 weeks prior to registration
  • Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
  • Known brain metastases or leptomeningeal metastases; NOTE: symptomatic, and/or if they require immunosuppressive doses of corticosteroids (e.g. > 10 mg/day prednisone or equivalents) for at least 2 weeks prior to study drug administration; patients with treated brain metastases who are deemed clinically stable and without radiological progression on positron emission tomography (PET), MRI or computed tomography (CT) scan performed =< 8 weeks of study entry, are not excluded; NOTE: primary nasopharyngeal cancers that directly invade the skull base and extend into the infratemporal fossa (e) are not regarded as brain metastases and are not excluded
  • 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
  • Any of the following:
  • Pregnant women
  • Nursing women
  • Men or women of childbearing potential who are unwilling to employ adequate contraception NOTE: breastfeeding should be discontinued if the mother is treated with nivolumab; women of childbearing potential and men must use two forms of contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; they must adhere to contraception for a period of 31 weeks after the last dose of nivolumab
  • For patients with unknown human immunodeficiency virus (HIV) status at the time of enrollment, HIV serology must be tested during screening; patients who are tested positive for HIV could be included if there is an adequate cluster of differentiation 4 (CD4) count (> 350/ul) on a stable regimen of highly active anti-retroviral therapy (HAART) with no detectable or minimal viral burden, and no active infections
  • For patients with unknown hepatitis B virus surface antigen (HbsAg) status, must be tested during study screening; patients who are tested positive test for HBsAg are excluded if they have inadequately controlled hepatitis B and/or Child-Pugh Class B or C cirrhosis; however, patients with adequately controlled hepatitis are not excluded from the study if they satisfy all of the following criteria: (i) must be receiving a nucleoside analog anti-viral drug for 3 or more months; and (ii) have a serum hepatitis B virus (HBV) deoxyribonucleic acid (DNA) level of less than 100 IU/ml via polymerase chain reaction quantification assays prior to enrollment
  • For patients with unknown hepatitis C virus ribonucleic acid (HCV antibody) status, must be tested during study screening; patients who are tested positive for HCV antibody are excluded from the study if they have inadequately controlled hepatitis C and/or Child-Pugh Class B or C cirrhosis; patients with adequately controlled hepatitis are not excluded from the study as defined by having undetectable level of serum HCV antibody level prior to enrollment; patients who are currently on interferon or other anti-HCV therapy will be excluded from study
  • 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; NOTE: 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, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded; patients 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
  • 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)
  • 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
  • Evidence of active or acute (i.e. current, or recent within 4 weeks prior to registration) diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation; patients with abdominal carcinomatosis, a history of non-recent intra-abdominal abscess, or a history of non-recent GI obstruction should be evaluated for the potential need for additional treatment before coming on study

Trial locations and contacts

19 sites in 3 countries.

19 sites in 3 countries

United States15 sites

  • University of Maryland/Greenebaum Cancer Center

    Baltimore, Maryland, 21201

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • Northwestern University

    Chicago, Illinois, 60611

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010

  • Los Angeles County-USC Medical Center

    Los Angeles, California, 90033

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • UC Comprehensive Cancer Center at Silver Cross

    New Lenox, Illinois, 60451

  • Keck Medical Center of USC Pasadena

    Pasadena, California, 91105

  • Mayo Clinic Cancer Center P2C

    Rochester, Minnesota, 55905

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • University of California Davis Comprehensive Cancer Center

    Sacramento, California, 95817

  • City of Hope South Pasadena

    South Pasadena, California, 91030

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Moffitt Cancer Center

    Tampa, Florida, 33612

Other trials in United States

Singapore3 sites

  • National University Hospital Singapore

    Singapore, 119074

  • National Cancer Centre

    Singapore, 169610

  • Johns Hopkins Singapore

    Singapore, 308433

Other trials in Singapore

China1 site

  • Chinese University of Hong Kong-Prince of Wales Hospital

    Shatin, Hong Kong

Other trials in China

About this study

Official title: Multicenter Phase II Study of Nivolumab in Previously Treated Patients With Recurrent and Metastatic Nasopharyngeal Carcinoma

This phase II trial studies how well nivolumab works in treating patients with nasopharyngeal cancer that has returned after a period of improvement (recurrent) and/or has spread to other parts of the body (metastatic). Monoclonal antibodies, such as nivolumab, may block tumor growth in different ways by targeting certain cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Objective tumor response to nivolumab in patients with previously treated recurrent and/or metastatic nasopharyngeal carcinoma (NPC) based on Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1.

SECONDARY OBJECTIVES:

  1. Tumor response to nivolumab based on immune-related response criteria (IRC). II. Duration of response. III. Progression-free survival and overall survival. IV. Safety and tolerability.

TERTIARY OBJECTIVES:

  1. To investigate the effect of nivolumab on tumor burden by analyzing the clearance of plasma Epstein-Barr virus (EBV) deoxyribonucleic acid (DNA) during the first 4-6 weeks of treatment.

II. To investigate the association between treatment outcome and immunological markers: a) Intratumoral expression of programmed cell death 1 (PD-1) and programmed cell death-ligand (PD-L1) in archived NPC tissues (mandatory); b) Serum absolute lymphocyte count at baseline and post-treatment (mandatory); and c) Plasma cytokine levels at baseline and serially during the first 8 weeks of treatment; d) Expression of PD-1 in cluster of differentiation (CD)8+ T cells in tumor infiltrating lymphocytes (TIL) at baseline (optional).

III. To investigate functional magnetic resonance imaging (MRI) sequences as an early predictor of response to nivolumab (optional only at Chinese University of Hong Kong [CUHK]).

OUTLINE:

Patients receive nivolumab intravenously (IV) over approximately 60 minutes on days 1 and 15. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 3 years.

Being tested
Laboratory Biomarker Analysis, Nivolumab
Medical subject headings
Nasopharyngeal Neoplasms, Nasopharyngeal Carcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • NivolumabBiological

    Also called BMS-936558, MDX-1106, NIVO, ONO-4538

    Given IV

Study groups in NCT02339558
Study groupRoleWhat they receive
Treatment (nivolumab)ExperimentalPatients receive nivolumab IV over approximately 60 minutes on days 1 and 15. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Receives: Other: Laboratory Biomarker Analysis; Biological: Nivolumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Confirmed Response Rate (Complete Response or Partial Response) Based on RECIST Version 1.1

    Confirmed response rate is defined as either a Complete Response (CR) or Partial Response (PR) based on RECIST version 1.1. > To be consider a CR, there must be a disappearance of all target lesions and each target lymph node must have reduction in short axis to < 1.0 cm.> > To be considered a PR, at least a 30% decrease in PBSD (sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation) taking as reference the baseline value.>

    > The confirmed response rate is reported as the number of patients reporting a CR or PR divided by the total number of evaluable patients multiplied by 100 (reported as a percentage).

    Measured: Up to 3 years

Secondary outcomes (5)

  1. Adverse Events

    Adverse events were collected and recorded according to the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine adverse event patterns. For this outcome measure, we summarize the worst graded adverse event regardless of treatment attribution per patient. All reported adverse events are reported in the Adverse Events section of this report.

    Measured: Up to 3 years on treatment

  2. Tumor Response to Nivolumab Based on the Immune Response Criteria (IRC)

    The Immune Response Criteria (IRC) is a response criteria derived from the WHO criteria.

    Measured: Up to 3 years

  3. Duration of Response

    Duration of response defined as the date at which the patient's objective status is first noted to be either a CR or PR to the date progression is documented, assessed according to RECIST version 1.1.

    Measured: Up to 3 years

  4. Progression-free Survival (PFS) Based on RECIST Version 1.1

    Progression Free Survival is defined as the time from registration to the time of death or progression, whichever occurs first. The distribution of PFS will be estimated using the method of Kaplan-Meier.

    Measured: Time from registration to the first of either death due to any cause or progression, assessed up to 3 years

  5. Overall Survival (OS)

    Overall survival is defined as the time from registration to the time of death. The distribution of survival time will be estimated using the method of Kaplan-Meier.

    Measured: Time from registration to death due to any cause, assessed up to 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Jan 2015 (estimated)
  2. Study start21 Jul 2015
  3. Primary completion16 Jun 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
45 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02339558
Sponsor's protocol ID
NCI-2014-02673
Other IDs
NCI-2014-02673, MC1471, 9742, 9742, N01CM00099, UM1CA186644, UM1CA186686, UM1CA186691
Status last verified
Aug 2019
First submitted
12 Jan 2015
Last updated
13 Sep 2019
Data monitoring committee
No

Publications

  • Ma BBY, Lim WT, Goh BC, Hui EP, Lo KW, Pettinger A, Foster NR, Riess JW, Agulnik M, Chang AYC, Chopra A, Kish JA, Chung CH, Adkins DR, Cullen KJ, Gitlitz BJ, Lim DW, To KF, Chan KCA, Lo YMD, King AD, Erlichman C, Yin J, Costello BA, Chan ATC. Antitumor Activity of Nivolumab in Recurrent and Metastatic Nasopharyngeal Carcinoma: An International, Multicenter Study of the Mayo Clinic Phase 2 Consortium (NCI-9742). J Clin Oncol. 2018 May 10;36(14):1412-1418. doi: 10.1200/JCO.2017.77.0388. Epub 2018 Mar 27.

    PubMed 29584545

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Laboratory Biomarker Analysis and Nivolumab in people with Nasopharyngeal Nonkeratinizing Carcinoma and Recurrent Nasopharynx Carcinoma, run by National Cancer Institute (NCI) at 19 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in United States, Singapore, China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Confirmed Response Rate (Complete Response or Partial Response) Based on RECIST Version 1.1 (time frame: Up to 3 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02339558, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Sep 2019.

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