Nivolumab in Treating Patients With Metastatic Adrenocortical Cancer

NCT02720484 | Terminated Phase 2 Results DMC

• 4 other identifiers: NU 15E01STU00202153P30CA060553NCI-2016-00194
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief 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. 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.

Conditions

Metastatic Carcinoma in the Adrenal Cortex; Recurrent Adrenal Cortex Carcinoma; Stage III Adrenal Cortex Carcinoma; Stage IV Adrenal Cortex Carcinoma

Outcome Measures

Primary Outcomes (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..

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

Secondary Outcomes (3)

• Progression-free Survival (PFS)

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

• Overall Survival (OS) at 3 Months and 6 Months

  At 3 months and 6 months from the initiation of treatment

• Toxicity of Nivolumab

  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)

Other Outcomes (6)

• Levels of Cytokines

  At baseline and at 4 weeks of treatment

• Levels of Peripheral Blood Lymphocyte Phenotype

  At baseline and at 4 weeks of treatment

• PD-L1 Expression

  At baseline and at 4 weeks of treatment

Study Arms (1)

Treatment (Nivolumab)

EXPERIMENTAL

Patients receive nivolumab IV over 30 minutes every 2 weeks in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Drug: Nivolumab

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (Nivolumab)

Nivolumab DRUG

Given IV

Also known as: BMS-936558, MDX-1106, ONO-4538, Opdivo

Treatment (Nivolumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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:
• 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)

Sponsors & Collaborators

• Northwestern University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Northwestern University

Chicago, Illinois, 60611, United States

Location

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Related Publications (1)

• 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.

  PMID: 31276163 DERIVED

MeSH Terms

Conditions

Adrenal Cortex Neoplasms

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Adrenal Gland Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Adrenal Cortex Diseases; Adrenal Gland Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

The study did not meet its first stage requirements of Interim analysis.

Results Point of Contact

• Title: Devalingam Mahalingam
• Organization: Northwestern University

mahalingam@northwestern.edu;

312.472.0564

Study Officials

• Benedito Carneiro, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2016
• First Posted: March 28, 2016
• Study Start: March 30, 2016
• Primary Completion: April 17, 2017
• Study Completion: November 2, 2018
• Last Updated: May 1, 2019
• Results First Posted: May 1, 2019

Record last verified: 2019-02

Locations

US (2)