Durvalumab and Epacadostat for Treatment of Unresectable, Recurrent, or Metastatic Epstein-Barr Virus Positive Nasopharyngeal Cancer

NCT04231864 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: 18209NCI-2019-06736
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This phase II trial studies how well durvalumab and epacadostat work in treating patients with Epstein-Barr virus positive nasopharyngeal cancer that cannot be removed by surgery (unresectable), has come back (recurrent), or has spread to other places in the body (metastatic). Epacadostat blocks the enzyme, IDO1, from working. Blocking this enzyme may allow for a stronger immune response against cancer. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body?s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving durvalumab and epacadostat may work better in treating patients with nasopharyngeal cancer compared to durvalumab alone.

Conditions

Epstein-Barr Virus Positive; Metastatic Nasopharyngeal Carcinoma; Recurrent Nasopharyngeal Carcinoma; Stage III Nasopharyngeal Carcinoma; Stage IV Nasopharyngeal Carcinoma; Stage IVA Nasopharyngeal Carcinoma; Stage IVB Nasopharyngeal Carcinoma

Outcome Measures

Primary Outcomes (1)

• Best overall response rate (BORR)

  Patients will meet the primary endpoint (BORR) if they attain a confirmed complete response (CR) or partial response (PR) with the combination treatment with a 4-week confirmatory scan. All response data will be determined using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The point estimate and two-sided exact binomial 95% confidence interval for the objective response rate will be provided.

  Up to 2 years

Secondary Outcomes (5)

• Progression free survival (PFS)

  up to 36 months

• Overall survival (OS)

  up to 36 months

• Duration of response (DoR)

  up to 36 months

• Biochemical Response to Treatment

  Up to 36 months

• Biochemical Verification of Drug Efficacy

  Up to 36 months

Study Arms (1)

Treatment (durvalumab, epacadostat)

EXPERIMENTAL

Patients receive durvalumab intravenously (IV) over 1 hour on day 1 and epacadostat orally (PO) twice a day (BID) on days 1-28. Cycles repeat every 28 days for 12 months in the absence of disease progression or unacceptable toxicity. Patients with disease progression who are benefiting from treatment in the opinion of the principal investigator may continue durvalumab and epacadostat for up to an additional 12 months from the initiation (or re-initiation) of treatment on study.

Biological: Durvalumab; Drug: Epacadostat

Interventions

Durvalumab BIOLOGICAL

Given intravenously (IV)

Also known as: Imfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI-4736, MEDI4736

Treatment (durvalumab, epacadostat)

Epacadostat DRUG

Given orally (PO)

Also known as: INCB 024360, INCB024360

Treatment (durvalumab, epacadostat)

Eligibility Criteria

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

You may qualify if:

• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Life expectancy of at least 4 months
• Patient is capable of giving signed informed consent and is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up
• Body weight \> 40 kilograms (kg)
• Patients must have a histological or cytological diagnosis of Epstein-Barr virus positive (EBV+) nasopharyngeal carcinoma that is not amenable to curative intent therapy (i.e. surgical resection, locoregional radiation therapy, concurrent chemoradiation)
• Patients must decline, be ineligible or intolerant to at least 1 standard treatment regimen in the advanced or metastatic setting, if such a therapy exists
• Patients must have disease progression within 6 months of completion of platinum-based concurrent chemoradiation or after platinum-based chemotherapy administered for the treatment of recurrent or metastatic disease
• If patient has known brain metastases, they must have stable neurologic status for at least 4 weeks without the use of steroids or on stable or decreasing dose of =\< 10 mg daily prednisone (or equivalent), and must be without neurologic dysfunction that would confound the evaluation of neurologic and other adverse events (AEs) (patients with a history of carcinomatous meningitis are not eligible)
• Patients may have had prior chemotherapy or immunotherapy or radiation therapy. Patients should discontinue prior medical therapy at least 5 drug half-lives or 28 days prior to the first dose of treatment on study (whichever is shorter). Patients should complete any prior radiation therapy at least 14 days prior to the initiation of treatment on study. Also, any drug related adverse events identified during prior therapy must be well controlled (typically resolution to =\< grade 1, OR resolved upon investigator review prior to initiation of this therapy
• No systemic antineoplastic therapy may be received by the patient between the time of the biopsy and the first administration of study treatment
• Patient must agree to any protocol mandated biopsies of tumor (deemed accessible, safe and appropriate for biopsy by the investigator?s assessment) and they must allow acquired tissue to be used for biomarker and immunological analysis
• For women of childbearing potential, negative serum or urine pregnancy test within 14 days to the first epacadostat, or durvalumab and use of birth control from 30 days prior to the first administration of treatment on study and 120 days following last day administration of treatment on study
• Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
• Women \< 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy)
• Women \>= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \> 1 year ago, had chemotherapy-induced menopause with last menses \> 1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy)

You may not qualify if:

• Active autoimmune disease that has required systemic treatment in past 2 years. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], systemic lupus erythematosus, sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, rheumatoid arthritis, uveitis, etc\]). The following are exceptions to this criterion:
• Patients with vitiligo or alopecia
• Patients with hypothyroidism (e.g., following Hashimoto syndrome or treated Graves disease) stable on hormone replacement
• Any chronic skin condition that does not require systemic therapy
• Patients without active disease in the last 5 years may be included but only after consultation with the study physician
• Patients with celiac disease controlled by diet alone
• Congestive heart failure (New York Heart Association class III to IV)
• History or presence of an abnormal electrocardiogram (ECG) that, in the investigator's opinion, is clinically meaningful. Screening corrected QT (QTc) interval \> 470 milliseconds is excluded. In the event that a single QTc is \> 470 milliseconds, the subject may enroll if the average QTc for the 3 ECGs is \< 470 milliseconds. For subjects with an intraventricular conduction delay (QRS interval \> 120 milliseconds), the corrected JT (JTc) interval may be used in place of the QTc with sponsor approval. The JTc must be \< 340 milliseconds if JTc is used in place of the QTc. Subjects with left bundle branch block are excluded
• Uncontrolled or clinically significant conduction abnormalities (e.g., ventricular tachycardia on anti-arrhythmics are excluded), 1st degree atrioventricular (AV) block or asymptomatic left anterior fascicular block (LAFB)/right bundle branch block (RBBB) are eligible
• Uncontrolled, symptomatic ischemia within 6 months of first dose of study treatment or known myocardial infarction in the previous six months
• Evidence of interstitial lung disease or any history of autoimmune pneumonitis including symptomatic and/or pneumonitis requiring treatment
• Infectious
• Evidence of significant active infection (e.g., pneumonia, cellulitis, wound abscess, etc.) requiring systemic therapy at time of study enrollment
• Active hepatitis B (hepatitis B surface antigen \[HBsAg\] reactive) associated the aspartate aminotransferase (AST) or alanine aminotransferase (ALT) elevations \> 1.5 x upper limit of normal (ULN). Patients who are HBsAg reactive must be on appropriate antiviral therapy while receiving treatment on study

Sponsors & Collaborators

• Alain Algazi: lead
• AstraZeneca: collaborator
• Incyte Corporation: collaborator

MeSH Terms

Conditions

Nasopharyngeal Carcinoma

Interventions

durvalumab; Immunoglobulin G; Disulfides; epacadostat

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals

Study Officials

• Alain P Algazi, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: January 14, 2020
• First Posted: January 18, 2020
• Study Start: December 1, 2020
• Primary Completion: April 1, 2022
• Study Completion: April 1, 2024
• Last Updated: October 26, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share