A Pilot Study to Investigate the Safety and Clinical Activity of Avelumab (MSB0010718C) in Thymoma and Thymic Carcinoma After Progression on Platinum-Based Chemotherapy
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|ClinicalTrials.gov Identifier: NCT03076554|
Recruitment Status : Recruiting
First Posted : March 10, 2017
Last Update Posted : April 19, 2021
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.
To test if avelumab is safe and well-tolerated, and is effective in treating relapsed or refractory thymoma and thymic carcinoma.
People ages 18 and older with thymoma or thymic carcinoma that has returned or progressed after platinum-containing chemotherapy
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.
|Condition or disease||Intervention/treatment||Phase|
|Thymoma Thymic Carcinoma||Drug: Avelumab||Phase 2|
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.
- 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.
- 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.
- 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 4.0.
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||55 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Pilot Study to Investigate the Safety and Clinical Activity of Avelumab (MSB0010718C) in Thymoma and Thymic Carcinoma After Progression on Platinum-Based Chemotherapy|
|Actual Study Start Date :||April 19, 2017|
|Estimated Primary Completion Date :||September 30, 2022|
|Estimated Study Completion Date :||September 30, 2023|
Experimental: Arm 1 Avelumab
Avelumab will be administered at a dose of 10 mg/kg intravenously once every two weeks until disease progression or development of intolerable adverseevents.
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.
- Safety and tolerability of Avelumab based on NCI-CTCAE v4.0 [ Time Frame: End of every cycle ]Toxicity profile based on NCI-CTCAE v4.0
- Objective Response Rate (ORR) based on RECIST 1.1 criteria [ Time Frame: 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
- Immune-related progression-free survival (irPFS) [ Time Frame: Date of progression ]Immune-related progression-free survival
- Overall Survival (OS) [ Time Frame: Date of death ]Overall survival
- Duration of Response [ Time Frame: Date of progression ]Time to progression
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03076554
|Contact: Shannon G Swift, R.N.||(240) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office 888-624-1937|
|Principal Investigator:||Arun Rajan, M.D.||National Cancer Institute (NCI)|