Clinical Trials /

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

Description:

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.

Related Conditions:
  • Thymic Carcinoma
  • Thymoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief 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
  • 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

Clinical Trial IDs

  • ORG STUDY ID: 170066
  • SECONDARY ID: 17-C-0066
  • NCT ID: NCT03076554

Conditions

  • Thymoma
  • Thymic Carcinoma

Interventions

DrugSynonymsArms
AvelumabArm 1

Purpose

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: - 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 patients with relapsed or
           refractory thymoma and thymic carcinoma.

        -  To determine the objective response rate (ORR) to Avelumab in patients with relapsed or
           refractory thymoma and thymic carcinoma.

      ELIGIBLITY:

        -  Patients 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 patients 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 patients 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.

        -  Toxicity will be assessed every cycle by CTCAE version 4.0.

        -  Tumor response will be assessed after completion of every other cycles (6 weeks) using
           RECIST criteria, version 1.1.

        -  When possible, a pre-treatment and post-treatment tumor biopsy will be conducted after
           completion of 2 cycles to evaluate treatment-related, intra-tumoral changes.
    

Trial Arms

NameTypeDescriptionInterventions
Arm 1Experimentalsingle-arm study; all patients will receive the same intervention
  • Avelumab

Eligibility Criteria

        -  INCLUSION CRITERIA:

          -  Patients must have histologically confirmed thymoma or thymic carcinoma by the
             pathology department/CCR/NCI.

          -  Patients must have had at least one prior line of platinum-based chemotherapy or
             patient must have refused cytotoxic chemotherapy. - Progressive disease must be
             documented prior to study entry and patients 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 patients from this trial).

          -  Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
             1.1.

          -  Male or female subjects aged greater than or equal to 18 years

             -- Because no dosing or adverse event data are currently available on the use of
             Avelumab in patients <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.

          -  Patients 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 subjects 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 both male and female subjects if the risk of
             conception exists. (Note: The effects of the study drug on the developing human fetus
             are unknown. Thus, women of childbearing potential and men 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

        contraceptive. Effective contraception must be used 30 days prior to first study drug
        administration, for the duration of trial participation, and at least for 60 days after
        last avelumab treatment administration if the risk of conception exists. Should a woman
        become pregnant or suspect she is pregnant while she or her partner is participating in
        this trial, the treating physician should be informed immediately.)

        -Pregnancy test: negative serum or urine pregnancy test at screening for women of
        childbearing potential.

        EXCLUSION CRITERIA:

          -  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 within 7 days before the start of trial treatment; or use of any
             investigational drug within 28 days before the start of trial treatment.

          -  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 immunestimulatory
             agent. Patients with diabetes type 1, vitiligo, psoriasis, pure red cell aplasia,
             Good s syndrome or hypo- or hyperthyroid diseases not requiring immunosuppressive
             treatment are eligible.

          -  Patients with symptomatic brain metastases will be excluded from trial secondary to
             poor prognosis. However, patients 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 v4.03 Grade greater than or equal to 3).

          -  Persisting toxicity related to prior therapy (NCI CTCAE v. 4.03 Grade > 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 women
             of childbearing potential. Women 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 women 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.

          -  Known alcohol or drug abuse.

          -  Clinically significant (i.e. active) cardiovascular disease: cerebral vascular
             accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months
             prior to enrollment), unstable angina, congestive heart failure greater than or equal
             to New York Heart Association Classification Class II, or serious cardiac arrhythmia
             requiring medication.

          -  All other severe acute or chronic medical conditions including colitis, inflammatory
             bowel disease, pneumonitis, pulmonary fibrosis or psychiatric conditions including
             recent (within the past year) or active suicidal ideation or behavior; or laboratory
             abnormalities that may increase the risk associated with study participation or study
             treatment administration or may interfere with the interpretation of study results
             and, in the judgment of the investigator, would make the patient inappropriate for
             entry into this study.

          -  Any psychiatric condition that would prohibit the understanding or rendering of
             informed consent.

          -  Legal incapacity or limited legal capacity.

          -  Non-oncology vaccine therapies for prevention of infection disease (e.g. seasonal flu
             vaccine, human papilloma virus vaccine) within 4 weeks of study drug administration.
             Vaccination while on study is also prohibited except for administration of
             inactivated vaccines (e.g. inactivated influenza vaccines).

          -  HIV-positive TET patients are ineligible because of the risk of developing
             opportunistic infections after treatment with an immune checkpoint inhibitor. Prior
             cases of disseminated herpes virus and fungal infections have been documented in this
             patient population.
      
Maximum Eligible Age:100 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety and tolerability of Avelumab based on NCI-CTCAE v4.0
Time Frame:End of every cycle
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Immune-related progression-free survival (irPFS)
Time Frame:Date of progression
Safety Issue:
Description:
Measure:Overall Survival (OS)
Time Frame:Date of death
Safety Issue:
Description:
Measure:Duration of Response
Time Frame:Date of progression
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:National Cancer Institute (NCI)

Trial Keywords

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

Last Updated

April 18, 2017