Avelumab for Recurrent/Metastatic Nasopharyngeal Cancer
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Avelumab Avelumab 10mg/kg IV infusion on days 1 and 15 of 28-day cycle |
Drug: 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.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Overall Response Rate [6 months]
Based on Response Evaluation Criteria in Solid Tumors (RECIST)
Eligibility Criteria
Criteria
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.
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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.
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Patient is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial.
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | UC San Diego Moores Cancer Center | La Jolla | California | United States | 92093 |
| 2 | Dana-Farber Cancer Institute | Boston | Massachusetts | United States | 02215 |
Sponsors and Collaborators
- Assuntina Sacco, M.D.
- Pfizer
Investigators
- Principal Investigator: Assuntina Sacco, MD, University of California Medical Center
Study Documents (Full-Text)
More Information
Publications
None provided.- 160114
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Avelumab |
|---|---|
| Arm/Group Description | 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. |
| Period Title: Overall Study | |
| STARTED | 5 |
| COMPLETED | 4 |
| NOT COMPLETED | 1 |
Baseline Characteristics
| Arm/Group Title | Avelumab |
|---|---|
| Arm/Group Description | 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. |
| Overall Participants | 4 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
49.25
(11.5)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
1
25%
|
| Male |
3
75%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
2
50%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
1
25%
|
| White |
1
25%
|
| More than one race |
0
0%
|
| Unknown or Not Reported |
0
0%
|
Outcome Measures
| Title | Overall Response Rate |
|---|---|
| Description | Based on Response Evaluation Criteria in Solid Tumors (RECIST) |
| Time Frame | 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Avelumab |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 2 |
| Progressive Disease at 6 months |
1
25%
|
| Stable Disease at 6 months |
1
25%
|
Adverse Events
| Time Frame | 2 years | |
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Avelumab | |
| Arm/Group Description | 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. | |
All Cause Mortality |
||
| Avelumab | ||
| Affected / at Risk (%) | # Events | |
| Total | 2/4 (50%) | |
Serious Adverse Events |
||
| Avelumab | ||
| Affected / at Risk (%) | # Events | |
| Total | 3/4 (75%) | |
| Blood and lymphatic system disorders | ||
| Anemia | 1/4 (25%) | |
| Gastrointestinal disorders | ||
| Abdominal pain | 1/4 (25%) | |
| General disorders | ||
| Non-cardiac chest pain | 1/4 (25%) | |
| Hepatobiliary disorders | ||
| Hepatic hemorrhage | 1/4 (25%) | |
| Infections and infestations | ||
| Sepsis | 1/4 (25%) | |
| Investigations | ||
| Blood bilirubin increased | 1/4 (25%) | |
| Respiratory, thoracic and mediastinal disorders | ||
| Pleural effusion | 1/4 (25%) | |
| Dyspnea | 1/4 (25%) | |
| Aspiration | 1/4 (25%) | |
| Epistaxis | 1/4 (25%) | |
Other (Not Including Serious) Adverse Events |
||
| Avelumab | ||
| Affected / at Risk (%) | # Events | |
| Total | 4/4 (100%) | |
| Blood and lymphatic system disorders | ||
| Anemia | 2/4 (50%) | |
| Gastrointestinal disorders | ||
| Abdominal pain | 1/4 (25%) | |
| Nausea | 1/4 (25%) | |
| Dysphagia | 1/4 (25%) | |
| Vomiting | 3/4 (75%) | |
| Gastroesophageal reflux disease | 1/4 (25%) | |
| General disorders | ||
| Fever | 1/4 (25%) | |
| Chills | 1/4 (25%) | |
| Non-cardiac chest pain | 1/4 (25%) | |
| Pain | 1/4 (25%) | |
| Edema limbs | 1/4 (25%) | |
| Hepatobiliary disorders | ||
| Hepatic hemorrhage | 1/4 (25%) | |
| Infections and infestations | ||
| Peritoneal infection | 1/4 (25%) | |
| Skin infection | 1/4 (25%) | |
| Papulopustular rash | 1/4 (25%) | |
| Tooth infection | 1/4 (25%) | |
| Investigations | ||
| Weight loss | 2/4 (50%) | |
| Metabolism and nutrition disorders | ||
| Hyponatremia | 2/4 (50%) | |
| Anorexia | 1/4 (25%) | |
| Respiratory, thoracic and mediastinal disorders | ||
| Dyspnea | 1/4 (25%) | |
| Cough | 1/4 (25%) | |
| Pleural effusion | 1/4 (25%) | |
| Epistaxis | 1/4 (25%) | |
| Postnasal drip | 1/4 (25%) | |
| Pneumonitis | 1/4 (25%) | |
| Skin and subcutaneous tissue disorders | ||
| Body odor | 1/4 (25%) | |
| Pruritis | 1/4 (25%) | |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr. Assuntina Sacco |
|---|---|
| Organization | UC San Diego - Moores Cancer Center |
| Phone | 858-822-5210 |
| agsacco@ucsd.edu |
- 160114