A Pilot Study to Investigate the Safety and Clinical Activity of Avelumab (MSB0010718C) in Thymoma and Thymic Carcinoma After Progression on Platinum-Based Chemotherapy
- Registration Number
- NCT03076554
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
Background:
Thymoma and thymic carcinoma are cancers originating in the thymus gland. Platinum-based chemotherapy is standard treatment for them. But not uncommonly, the disease returns and people need more treatment to keep the cancer from growing. The drug Avelumab could help the immune system fight cancer.
Objective:
To test if avelumab is safe and well-tolerated, and is effective in treating relapsed or refractory thymoma and thymic carcinoma.
Eligibility:
People ages 18 and older with thymoma or thymic carcinoma that has returned or progressed after platinum-containing chemotherapy
Design:
Participants will be screened with:
* Blood, urine, and heart tests
* Scan: They lie in a machine that takes pictures of the body.
* Physical exam
* Medical history
* Biopsy: a needle removes a piece of tumor. Samples can be from a previous procedure, although it is desirable to undergo a new biopsy.
Participants will have treatment in 2-week cycles. They will continue until the side effects are not tolerable or their disease gets worse. Visits at the following time points are required per protocol. Patients who respond to treatment or have durable stability after at least 12 months of therapy may undergo a dose de-escalation regimen to continue on therapy.
* Every 2 weeks: Participants will get avelumab by infusion in a vein (IV). They will get diphenhydramine (benadryl) and acetaminophen (tylenol) by mouth or IV before receiving avelumab to decrease the chances of developing a reaction to avelumab. They will have blood, urine, and heart tests periodically.
* Cycles 4 and 7, then every 6 weeks: Scans will be performed to look for shrinkage or growth of tumor.
* Cycle 4: Participants will be offered a chance to undergo a biopsy.
* 2-4 weeks after stopping treatment: Blood, urine, and heart tests will be performed. Participants might undergo a scan.
* 10 weeks after stopping treatment: Blood, urine, and heart tests.
* About 6 months after stopping treatment, then every 3 months: Participants will have scans andcan allow genetic testing on their blood and tissue samples.
- Detailed Description
Background
Platinum-based chemotherapy is the standard of care for advanced unresectable thymic epithelial tumors (TETs). However more than half of these patients experience disease recurrence and require second-line therapy. There are no approved drugs for treatment of recurrent thymoma and thymic carcinoma and new therapeutic options are needed for patients who have disease progression on or after platinum-containing therapy. The clinical activity of checkpoint blockade targeting programmed death 1 (PD-1) and its ligand (PD-L1) has been demonstrated against various tumor types. We have demonstrated the ability of avelumab to induce major responses in patients with advanced thymoma in a phase I dose escalation study. Further investigation of avelumab in patients with TETs is needed to define the clinical activity and safety of immune checkpoint blockade in patients with TETs.
Primary Objectives
To determine the safety and tolerability of avelumab in participants with relapsed or refractory thymoma and thymic carcinoma.
To determine the objective response rate (ORR) to avelumab in participants with relapsed or refractory thymoma and thymic carcinoma.
Eligibility
Participants with histologically confirmed, unresectable thymoma or thymic carcinoma who have previously been treated with at least one platinum-containing chemotherapy regimen with progressive disease prior to study entry
Prior treatment with immune checkpoint inhibitors is permitted if the reason for discontinuation was not disease progression or life-threatening adverse events (laboratory abnormalities alone with prior therapy will not exclude participants from this trial)
Measurable disease by RECIST 1.1 criteria
Adequate renal, hepatic and hematopoietic function
No major surgery, radiotherapy, chemotherapy or biologic therapy within 28 days of avelumab
No prior thymic tumor-associated autoimmune disease with the exception of pure red cell aplasia and vitiligo.
Design
This will be a single-arm, pilot study to determine the clinical activity and safety of treatment with avelumab in participants with relapsed or refractory thymoma and thymic carcinoma.
Avelumab will be administered at a dose of 10 mg/kg intravenously once every two weeks until disease progression or development of intolerable adverse events. The two week period will constitute one cycle.
Per the study team s discretion, participants who respond to treatment or have durable stability after at least 12 months of therapy may undergo a dose de-escalation regimen to continue on therapy.
Toxicity will be assessed every cycle by CTCAE version 5.0.
Tumor response will be assessed after completion of every third cycle (6 weeks) using RECIST criteria, version 1.1.
When possible, a tumor biopsy will be conducted pre-treatment and on C4D43 to evaluate treatment-related, intra-tumoral changes.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 60
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Arm 1 Avelumab Avelumab Avelumab will be administered at a dose of 10 mg/kg intravenously once every two weeks until disease progression or development of intolerable adverse events.
- Primary Outcome Measures
Name Time Method Safety and tolerability of Avelumab based on NCI-CTCAE v4.0 End of every cycle Toxicity profile based on NCI-CTCAE v4.0
Objective Response Rate (ORR) based on RECIST 1.1 criteria Every other cycle Objective response rate; i.e., the number of participants with complete response + the number with partial response confirmed via RECIST 1.1
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) Date of death Overall survival
Immune-related progression-free survival (irPFS) Date of progression Immune-related progression-free survival
Duration of Response Date of progression Time to progression
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States