Nasopharyngeal Cancer
Conditions
Keywords
Nasopharyngeal, PD-L1, monoclonal antibody, Epstein-barr virus
Brief summary
The purpose of this study is to determine whether avelumab, an investigational antibody against programmed death-ligand (PD-L1), has an effect on recurrent nasopharyngeal cancer. Avelumab is designed to block the interaction between programmed cell death protein 1 (PD-1), a known immune checkpoint, and PD-L1. By blocking this interaction, the immune system may be stimulated, allowing it to more effectively recognize and attack the cancer.
Detailed description
This is a prospective, multi-center, open-label, single-arm phase II trial to evaluate the efficacy of Avelumab for patients with recurrent/metastatic, Epstein-Barr virus (EBV)-related nasopharyngeal carcinoma. Upon study entry, all patients will receive Avelumab 10 milligrams per kilogram (mg/kg) intravenously (IV) on days 1 and 15 of each 28-day cycle. Treatment will be given until disease progression, unacceptable toxicity, investigator decision or patient withdrawal. Dose interruptions may occur per pre-specified criteria for grade 3 or higher toxicity.
Interventions
DRUGAvelumab
Avelumab 10mg/kg IV on days 1 and 15 of each 28-day cycle. Treatment will be given until disease progression, unacceptable toxicity, investigator decision or patient withdrawal.
Sponsors
Pfizer
Assuntina Sacco, M.D.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient has histologically/cytologically confirmed, non-keratinizing/undifferentiated, EBV-related nasopharyngeal carcinoma, not amenable to curative intent therapy. EBV testing may be completed per institutional standards. * Patient must have at least one measurable site of disease as defined by RECIST v1.1, determined by investigator review * Patient has received at least one prior line of systemic therapy in the recurrent/metastatic setting * Patient is willing to undergo a fresh tumor biopsy (core or excisional) for correlative analyses (ie. PD-L1 expression).The study chair may grant exceptions to the mandatory biopsy should the treating physician deem that a biopsy is not feasible or unsafe for the patient, and archival tissue is available and provided for study purposes. A conversation with the study chair is required to obtain an exception. * Patient has adequate organ and marrow function. * Female patient of childbearing potential has a negative serum or urine pregnancy within 72 hours prior to receiving the first dose of study medication
Exclusion criteria
* Patient is currently receiving or has received another investigational agent within 4 weeks prior to Day 1 of study. * Patient has received chemotherapy or radiotherapy within 4 weeks prior to Day 1 of study. Prior palliative radiotherapy to metastatic lesion(s) is permitted, provided there is at least one measurable lesion that has not been radiated. * Patient has received prior immunotherapy with inhibitors of PD-1/PD-L1 axis. * Patient has had major surgery or insufficient recovery from surgical-related trauma or wound healing within 14 days of Study Day 1. * Patient has had a prior Grade ≥ 3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE \> Grade 1. * Patient has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. * Patient has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability. * Patient has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs).Patients with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment within the past 2 years are not excluded.Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. * Patient has a diagnosis of immunodeficiency, or is receiving systemic steroid therapy (\>10mg prednisone daily, or steroid equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of avelumab. * Patient has a known history of active TB (Bacillus Tuberculosis). * Patient has a known history of, or any evidence of active, non-infectious pneumonitis. * Patient has a known history of chronic interstitial lung disease. * Patient has an active infection requiring systemic therapy. * Patient is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial. * Patient has known active Hepatitis B infection (defined as presence of HepB sAg and/ or Hep B DNA), active hepatitis C infection (defined as presence of Hep C RNA) and/or known Human Immunodeficiency Virus (HIV). Patients with HIV who have a normal CD4 count (≥ 200) and an undetectable viral load are not excluded. * Patient has received a live vaccine within 30 days of study Day 1.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | 6 months | Based on Response Evaluation Criteria in Solid Tumors (RECIST) |
Countries
United States
Participant flow
Pre-assignment details
Description of discrepancy between the enrollment number in the Protocol Section (6) and number of participants Started in the Participant Flow module (5): there were a total of six participants who signed consent for the study. One of the participants was a screen fail. Another participant withdrew consent prior to completing screening procedures. When determining the number of participants enrolled, these two participants were still considered. The correct enrollment number should be four.
Participants by arm
| Arm | Count |
|---|---|
| Avelumab Avelumab 10mg/kg IV infusion on days 1 and 15 of 28-day cycle
Avelumab: Avelumab 10mg/kg IV on days 1 and 15 of each 28-day cycle. Treatment will be given until disease progression, unacceptable toxicity, investigator decision or patient withdrawal. | 4 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Screen Failure | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Avelumab |
|---|---|
| Age, Continuous | 49.25 years STANDARD_DEVIATION 11.5 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 4 |
| other Total, other adverse events | 4 / 4 |
| serious Total, serious adverse events | 3 / 4 |
Outcome results
Primary
Overall Response Rate
Based on Response Evaluation Criteria in Solid Tumors (RECIST)
Time frame: 6 months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Avelumab | Overall Response Rate | Progressive Disease at 6 months | 2 Participants |
| Avelumab | Overall Response Rate | Stable Disease at 6 months | 2 Participants |