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Metastatic Carcinoma in the Adrenal CortexPhase 2NCT02720484

Nivolumab in Treating Patients With Metastatic Adrenocortical Cancer

A Phase 2 study testing Laboratory Biomarker Analysis and Nivolumab in people with Metastatic Carcinoma in the Adrenal Cortex and Recurrent Adrenal Cortex Carcinoma, run by Northwestern University at 2 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The primary objective will be to assess overall response rate of nivolumab in patients with metastatic or locally advanced adrenocortical carcinoma. Nivolumab was recently approved by U.S. Food and Drug Administration (FDA) for the treatment of advanced melanoma, non-small cell lung cancer and renal cell carcinoma. 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
10 participants
Where
2 sitesUnited States
Study dates
30 Mar 2016to 2 Nov 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

  • Patients must have a histologically confirmed stage IV or unresectable locally advanced adrenocortical carcinoma
  • Patients must have disease progressing after treatment with at least one line of therapy including mitotane and/or chemotherapy; Note: patients declining first line treatment with mitotane and/or chemotherapy based on limited efficacy are also eligible for this study
  • Patients must have measurable disease according to the standard RECIST version 1.1; CT scans or magnetic resonance imaging (MRIs) used to assess the measurable disease must have been completed within 28 days prior to registration
  • Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0-3
  • Leukocytes >= 2,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
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  • Hemoglobin >= 9 g/dL
  • Platelets >= 100,000/mcL
  • Total bilirubin =< 1.5 × institutional upper limit of normal (ULN) (except patients with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)
  • Aspartate transaminase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine transferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN
  • Serum creatinine of < 3.0 x ULN (upper limit of normal) or creatinine clearance (CrCl) > 30 mL/minute (using Cockcroft/Gault formula below)
  • Patients with history of central nervous system (CNS) metastases are eligible if CNS disease has been radiographically and neurologically stable for at least 6 weeks prior to study registrations and do not require corticosteroids (of any dose) for symptomatic management
  • Females of childbearing potential (FOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 72 hours prior to the start of study drug; NOTE: a FOCBP is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: has not undergone a hysterectomy or bilateral oophorectomy; has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for > 12 months)
  • FOCBP must agree to follow instructions for method(s) of contraception (e.g. hormonal or barrier method of birth control; abstinence) for the duration of treatment with nivolumab plus 5 half-lives of nivolumab (19 weeks) plus 30 days (duration of ovulatory cycle) for a total of 23 weeks post-treatment completion
  • Males who are sexually active with women of childbearing potential (WOCBP) must agree to follow instructions for method(s) of contraception (e.g. hormonal or barrier method of birth control; abstinence) for the duration of treatment with nivolumab plus 5 halflives of the study drug (19 weeks) plus 90 days (duration of sperm turnover) for a total of 31 weeks days post-treatment completion
  • Patients must have the ability to understand and the willingness to sign a written informed consent prior to registration on study

Who cannot join

  • Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study are not eligible
  • Patients who have not recovered to =< grade 1 from adverse events due to agents administered more than 4 weeks earlier are not eligible
  • Patients may not be receiving any other investigational agents
  • Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab are not eligible
  • Patients should be excluded if they have had prior treatment with an anti-PD1 or anti-PD-L1. Please contact principal investigator, Benedito Carneiro, for specific questions on potential interactions
  • 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:
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  • 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
  • Patients with a history of toxic epidermal necrolysis (TEN)
  • Stevens-Johnson syndrome
  • Anti-phospholipid syndrome; Note: subjects with 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 are permitted to enroll
  • Any condition requiring systemic treatment with corticosteroids (> 10mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to first dose of study drug; Note: inhaled steroids and adrenal replacement steroid doses > 10mg daily prednisone equivalents are permitted in the absence of active autoimmune disease; a brief (less than 3 weeks) course of corticosteroids for prophylaxis (eg, contrast dye allergy) or for treatment of non-autoimmune conditions (eg, delayed-type hypersensitivity reaction caused by a contact allergen) is permitted
  • Patients who have an uncontrolled intercurrent illness including, but not limited to any of the following, are not eligible
  • Hypertension that is not controlled on medication (Note: hypertension is defined as blood pressure >= 140/90)
  • Ongoing or active infection requiring systemic treatment
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Psychiatric illness/social situations that would limit compliance with study requirements
  • Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient's safety or study endpoints
  • Female patients who are pregnant or nursing are not eligible
  • 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
  • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) is not permitted
  • Any known positive test for hepatitis B or hepatitis C virus indicating acute or chronic infection is not permitted

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Northwestern University

    Chicago, Illinois, 60611

  • The Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

Other trials in United States

About this study

Official title: Phase II Study of Nivolumab (Anti-PD-1 Antibody) for Treatment of Metastatic Adrenocortical Carcinoma

The primary objective will be to assess overall response rate of nivolumab in patients with metastatic or locally advanced adrenocortical carcinoma. Nivolumab was recently approved by U.S. Food and Drug Administration (FDA) for the treatment of advanced melanoma, non-small cell lung cancer and renal cell carcinoma. It is considered investigational for the treatment of advanced or refractory adrenocortical carcinoma. "Investigational" means that the drug is not approved by the USFDA or not approved for the indication under investigation. Nivolumab could shrink adrenocortical carcinoma but it could also cause side effects. Researchers hope to learn if the study drug will shrink the cancer and hopefully to relieve symptoms that are related to the cancer.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To assess overall response rate of nivolumab in patients with metastatic or locally advanced adrenocortical carcinoma (ACC).

SECONDARY OBJECTIVES:

  1. To assess the progression free survival defined as time from date of first nivolumab infusion until date of death or evidence of progression of disease as assessed by computed tomography (CT) imaging every 8 weeks according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1.

II. To assess the overall survival defined as time from date of first nivolumab infusion until death of patients with metastatic or locally advanced ACC.

III. To assess the safety and tolerability profile of nivolumab described by number, frequency, and severity of adverse events according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.3 assessed every 2 weeks while patients are on therapy.

TERTIARY OBJECTIVES:

  1. To assess the overall response rate, progression free survival and overall survival according to tumor programmed cell death 1 ligand 1 (PD-L1) and programmed cell death 1 ligand 2 (PD-L2) expression.

II. To assess the overall response rate, progression free survival and overall survival according to serum interleukin levels and peripheral T cell profile levels.

III. To measure humoral and cellular responses to tumor antigens on serum samples by measuring the levels of cytokines (ie, interleukin [IL] -2, IL-6, IL-8, IL-10, IL-18, interferon [IFN] gamma and tumor necrosis factor [TNF]-alpha) and peripheral blood lymphocyte phenotype.

OUTLINE:

Patients receive nivolumab intravenously (IV) over 30 minutes every 2 weeks in the absence of disease progression or unacceptable toxicity, or withdrawal of consent.

After completion of study treatment, patients are followed up every 3 months for up to 2 years.

Being tested
Laboratory Biomarker Analysis, Nivolumab
Medical subject headings
Adrenal Cortex Neoplasms

What participants receive

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

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • NivolumabDrug

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

    Given IV

Study groups in NCT02720484
Study groupRoleWhat they receive
Treatment (Nivolumab)ExperimentalPatients receive nivolumab IV over 30 minutes every 2 weeks in the absence of disease progression or unacceptable toxicity.
Receives: Other: Laboratory Biomarker Analysis; Drug: Nivolumab

What is being measured

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

  1. Overall Response Rate

    Overall Response Rate of nivolumab treatment for patients with metastatic adrenocortical carcinoma will be measured per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI scans every 8 weeks:

    Complete Response (CR) = disappearance of all target lesions. Partial Response (PR) >=30% decrease in the sum of the longest diameter of target lesions (should be confirmed 8 weeks after initial response otherwise considered unconfirmed PR).

    Stable Disease, neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters while on study.

    Progressive Disease, defined as having at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions..

    Measured: From the start of treatment and every 8 weeks/2 cycles with a range of cycles attempted 1-15.

Secondary outcomes (3)

  1. Progression-free Survival (PFS)

    Progression Free Survival (PFS) of nivolumab treatment in patients with metastatic adrenocortical carcinoma is defined as the duration of time from start of treatment to time of documented progression or death, whichever comes first. It will measured per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI scans every 8 weeks.

    Measured: From start of treatment and every 8 weeks/2 cycles until progressive disease or death. Median follow up of 4.5 months

  2. Overall Survival (OS) at 3 Months and 6 Months

    Overall Survival (OS) of nivolumab treatment in patients with metastatic adrenocortical carcinoma and will be defined as the duration of time from treatment initiation until death. OS will be assessed as the percentage of patients alive at 3 months and at 6 months from initiation of treatment on study.

    Measured: At 3 months and 6 months from the initiation of treatment

  3. Toxicity of Nivolumab

    Safety and tolerability profile of Nivolumab will be assessed by describing by number, frequency, and severity of Adverse Events (AEs) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.3. All AEs that were considered related to Nivolumab were collected and are shown below. Patients with multiple events in the same category are counted only once in that category. Patients with events in more than one category are counted in each of those categories. Categories with no events are not shown.

    In general AEs will be graded according to the following:

    Grade 1 = Mild AE Grade 2= Moderate AE Grade 3 = Severe AE Grade 4 = Life-threatening or disabling AE Grade 5 = Death related to AE

    Measured: From treatment initiation, twice every Cycle (every 14 days) while on treatment, up to 12 weeks after final dose. Range of cycles completed 1-15 (1 Cycle=28 days)

Timeline

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

  1. First posted28 Mar 2016 (estimated)
  2. Study start30 Mar 2016
  3. Primary completion17 Apr 2017
  4. Study completion2 Nov 2018

Why it stopped: Study did not meet first stage requirements of interim analysis

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
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02720484
Sponsor's protocol ID
NU 15E01
Other IDs
STU00202153, NU 15E01, P30CA060553, NCI-2016-00194
Status last verified
Feb 2019
First submitted
16 Mar 2016
Last updated
1 May 2019
Data monitoring committee
Yes

Publications

  • Carneiro BA, Konda B, Costa RB, Costa RLB, Sagar V, Gursel DB, Kirschner LS, Chae YK, Abdulkadir SA, Rademaker A, Mahalingam D, Shah MH, Giles FJ. Nivolumab in Metastatic Adrenocortical Carcinoma: Results of a Phase 2 Trial. J Clin Endocrinol Metab. 2019 Dec 1;104(12):6193-6200. doi: 10.1210/jc.2019-00600.

    PubMed 31276163

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Laboratory Biomarker Analysis and Nivolumab in people with Metastatic Carcinoma in the Adrenal Cortex and Recurrent Adrenal Cortex Carcinoma, run by Northwestern University at 2 sites in United States.

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 16 inclusion and 33 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: stopped early, as of the sponsor's last update on 1 May 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. 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 1 May 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?

Overall Response Rate (time frame: From the start of treatment and every 8 weeks/2 cycles with a range of cycles attempted 1-15.). 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 NCT02720484, 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 1 May 2019.

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