A Pilot Study to Investigate the Safety and Clinical Activity of Avelumab (MSB0010718C) in Thymoma and Thymic Carcinoma After Progression on Platinum-Based Chemotherapy

NCT03076554 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: 17006617-C-0066
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

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.

Conditions

Thymic Carcinoma; Thymoma

Keywords

Programmed Death 1 (PD-1); Immune Checkpoint Blockade

Outcome Measures

Primary Outcomes (2)

• Safety and tolerability of Avelumab based on NCI-CTCAE v4.0

  Toxicity profile based on NCI-CTCAE v4.0

  End of every cycle

• Objective Response Rate (ORR) based on RECIST 1.1 criteria

  Objective response rate; i.e., the number of participants with complete response + the number with partial response confirmed via RECIST 1.1

  Every other cycle

Secondary Outcomes (3)

• Immune-related progression-free survival (irPFS)

  Date of progression

• Overall Survival (OS)

  Date of death

• Duration of Response

  Date of progression

Study Arms (1)

Arm 1 Avelumab

EXPERIMENTAL

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.

Drug: Avelumab

Interventions

Avelumab DRUG

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.

Arm 1 Avelumab

Eligibility Criteria

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

You may qualify if:

• Participants must have histologically confirmed thymoma or thymic carcinoma by the pathology department/CCR/NCI.
• Participants must have had at least one prior line of platinum-based chemotherapy or participant must have refused cytotoxic chemotherapy. Progressive disease must be documented prior to study entry and participants must have advanced, unresectable disease that is not amenable to surgical resection.
• Prior treatment of PD-1 or PD-L1-directed immune checkpoint blockade is permitted if treatment was not discontinued due to disease progression or lifethreatening adverse events per the investigators discretion (laboratory abnormalities alone with prior therapy will not exclude participants from this trial).
• Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST 1.1.
• Individuals aged greater than or equal to 18 years
• \-- Because no dosing or adverse event data are currently available on the use of Avelumab in participants \<18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
• ECOG performance status less than or equal to 1.
• Participants must have normal organ and marrow function as defined below:
• absolute neutrophil count: greater than or equal to 1,500/mm\^3 OR greater than or equal to 1.5 x 10\^9/L
• platelets greater than or equal to 100,000/mm\^3 OR greater than or equal to 100 x 10\^9/L
• hemoglobin greater than or equal to 9g/dL (may have been transfused)
• total bilirubin less than or equal to 1.5 x the upper limit of normal range(ULN)
• AST(SGOT)/ALT(SGPT) less than or equal to 2.5 x ULN OR less than or equal to 5 x ULN for participants with documented metastatic disease to the liver
• creatinine clearance greater than or equal to 30 mL/min according to the Cockcroft Gault formula (or local institutional standard method)
• Highly effective contraception for all individuals if the risk of conception exists. (Note: The effects of the study drug on the developing human fetus are unknown. Thus, individuals of childbearing potential and those able to father a child must agree to use highly effective contraception, defined as 2 barrier methods, or 1 barrier method with a spermicide, an intrauterine device or use of oral female

You may not qualify if:

• Concurrent treatment with a non-permitted drug
• Concurrent anticancer treatment within 28 days before the start of trial treatment (e.g., cytoreductive therapy, radiotherapy \[with the exception of palliative bone directed radiotherapy\], immune therapy, or cytokine therapy except for erythropoietin); major surgery within 28 days before the start of trial treatment (excluding prior diagnostic biopsy); concurrent systemic therapy with immunosuppressive agents within 28 days before the start of trial treatment; use of hormonal agents for the treatment of thymic cancer within 7 days before the start of trial treatment; or use of any investigational drug within 28 days before the start of trial treatment.
• Note: Individuals receiving bisphosphonate or denosumab are eligible provided treatment was initiated at least 14 days before the first dose of avelumab.
• History of previous malignant disease within the last 2 years with the following exceptions: basal or squamous cell carcinoma of the skin, cervical carcinoma in situ, ductal carcinoma in situ of the breast, papillary or follicular thyroid carcinoma, and non-muscle invasive bladder cancer.
• Active autoimmune disease that might deteriorate when receiving an immune-stimulatory agent. Participants with diabetes type 1, vitiligo, psoriasis, pure red cell aplasia, Good s syndrome or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible. Anti-acetylcholine receptor antibodies will be checked during screening. Participants will be ineligible if results are positive, even if there is no clinical history of autoimmune disease.
• Participants with symptomatic brain metastases will be excluded from trial secondary to poor prognosis. However, participants who have had treatment for their brain metastasis and whose brain disease has remained stable for 3 months without steroid therapy may be enrolled.
• Active infection requiring systemic therapy or significant acute or chronic infections including, among others:
• Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive).
• Known history of testing positive for HIV or known acquired immunodeficiency syndrome.
• Prior organ transplantation including allogenic stem-cell transplantation.
• Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v5 Grade greater than or equal to 3).
• Persisting toxicity related to prior therapy (NCI CTCAE v5Grade \> 1) however, alopecia, sensory neuropathy Grade less than or equal to 2, or other Grade less than or equal to 2 not constituting a safety risk based on investigator s judgment are acceptable.
• Pregnancy or lactation period. Note: a negative pregnancy test is required for individuals of childbearing potential. Individuals who are postmenopausal (age-related amenorrhea greater than or equal to 12 consecutive months or follicle-stimulating hormone (FSH) \> 40 milli international units per milliliter \[mIU/ml\]), or who had undergone hysterectomy or bilateral oophorectomy are exempt from pregnancy testing. If necessary to confirm postmenopausal status a FSH level will be included at screening.
• Pregnant individuals are excluded from this study because Avelumab is in the class of agents known as antineoplastics/monoclonal antibodies with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in
• nursing infants secondary to treatment of the mother with Avelumab, breastfeeding should be discontinued if the mother is treated with Avelumab.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Katsuya Y, Fujita Y, Horinouchi H, Ohe Y, Watanabe S, Tsuta K. Immunohistochemical status of PD-L1 in thymoma and thymic carcinoma. Lung Cancer. 2015 May;88(2):154-9. doi: 10.1016/j.lungcan.2015.03.003. Epub 2015 Mar 10.

  PMID: 25799277 BACKGROUND

• Padda SK, Riess JW, Schwartz EJ, Tian L, Kohrt HE, Neal JW, West RB, Wakelee HA. Diffuse high intensity PD-L1 staining in thymic epithelial tumors. J Thorac Oncol. 2015 Mar;10(3):500-8. doi: 10.1097/JTO.0000000000000429.

  PMID: 25402569 BACKGROUND

• Remon J, Girard N, Novello S, de Castro J, Bigay-Game L, Bernabe R, Greillier L, Mosquera J, Cousin S, Juan O, Sampayo M, Besse B. PECATI: A Multicentric, Open-Label, Single-Arm Phase II Study to Evaluate the Efficacy and Safety of Pembrolizumab and Lenvatinib in Pretreated B3-Thymoma and Thymic Carcinoma Patients. Clin Lung Cancer. 2022 May;23(3):e243-e246. doi: 10.1016/j.cllc.2021.07.008. Epub 2021 Jul 20.

  PMID: 34393061 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Thymoma; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

avelumab

Condition Hierarchy (Ancestors)

Neoplasms, Complex and Mixed; Neoplasms by Histologic Type; Neoplasms; Thymus Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lymphatic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Arun Rajan, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2017
• First Posted: March 10, 2017
• Study Start: April 19, 2017
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2027
• Last Updated: April 24, 2026

Record last verified: 2026-04-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active.
• Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI. Genomic data are made available via dbGaP through requests to the data custodians.

Locations

US (1)