Localized Radiation Therapy or Recombinant Interferon Beta and Avelumab With or Without Cellular Adoptive Immunotherapy in Treating Patients With Metastatic Merkel Cell Carcinoma

NCT02584829 | Terminated Phase 1 Results DMC FDA Drug

• 7 other identifiers: 9245NCI-2014-02462FHCRC 9245K24CA139052P30CA015704R01CA176841RG1015013
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial studies the side effects and how well localized radiation therapy or recombinant interferon beta and avelumab with or without cellular adoptive immunotherapy works in treating patients with Merkel cell carcinoma that has spread to other parts of the body. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Interferon beta is a substance that can improve the body's natural response and may interfere with the growth of tumor cells. Monoclonal antibodies, such as avelumab, may help T lymphocytes kill tumor cells. For cellular adoptive immunotherapy, specific white blood cells are collected from the patient's blood and treated in the laboratory to recognize Merkel cell carcinoma. Infusing these cells back into the patient may help the body build an effective immune response to kill Merkel cell carcinoma. Giving localized radiation therapy or recombinant interferon beta and avelumab with or without cellular adoptive immunotherapy may be a better treatment for Merkel cell carcinoma.

Conditions

Merkel Cell Polyomavirus Infection; Stage IV Merkel Cell Carcinoma AJCC v7

Outcome Measures

Primary Outcomes (2)

• Evidence of Response, Based on Median Time to New Metastasis

  Median time to new metastases reported for each group below. Group 1 result is NA, patient had no new detectable metastases in study follow-up period. Arm I is not analyzed because the one patient in Arm I did not experience new metastasis in their followup period, so they are not evaluable.

  Up to 1 year

• Count of Participants Who Experienced Adverse Events, Evaluated According to the Current Guidelines in National Cancer Institute (NCI) Common Toxicity Criteria Version 4.0

  Evidence and nature of toxicity related to the treatment will be assessed and compared between groups.

  Up to 4 weeks after the last infusion

Secondary Outcomes (5)

• Disease Response, as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1

  28 days post infusion

• Count of Participants That Displayed Evidence of Epitope Spreading

  Up to 3 months

• Functional Capacity of Transferred T Cells (Group 2)

  Up to 3 months

• Merkel Cell Carcinoma (MCC)-Specific Survival

  Up to 1 year

• Count of Participants Who Displayed Persistence of Transferred T Cells in Blood and Tumor (Group Co2)

  Up to 90 days post infusion

Study Arms (2)

Group 1 (avelumab and MHC class I up-regulation)

EXPERIMENTAL

Patients who do not have a HLA type for which T cells can be generated or for whom T cells cannot be generated for technical issues receive avelumab intravenously (IV) over 1 hour every 2 weeks for 12 months. Within 7-10 days after completion of 1-3 doses of avelumab, patients receive MHC class I up-regulation intervention comprising either localized radiation therapy or recombinant interferon beta via intra-tumor injection.

Drug: Avelumab; Other: Laboratory Biomarker Analysis; Radiation: Radiation Therapy; Biological: Recombinant Interferon Beta

Group 2 (avelumab, MHC class I up-regulation, T cells)

EXPERIMENTAL

Patients who have an HLA type for which T cells can be generated receive avelumab IV over 1 hour every 2 weeks for 12 months. Patients also receive MHC class I up-regulation intervention as in Group 1 between 7-10 days after the first infusion of avelumab and 2-5 days before the first infusion of MCPyV TAg-specific polyclonal autologous CD8+ T cells. Patients receive two infusions of MCPyV TAg-specific polyclonal autologous CD8+ T cells IV over 60-120 minutes.

Drug: Avelumab; Other: Laboratory Biomarker Analysis; Biological: MCPyV TAg-specific Polyclonal Autologous CD8-positive T Cells; Radiation: Radiation Therapy; Biological: Recombinant Interferon Beta

Interventions

Avelumab DRUG

Given IV

Also known as: Bavencio, MSB-0010718C, MSB0010718C

Group 1 (avelumab and MHC class I up-regulation); Group 2 (avelumab, MHC class I up-regulation, T cells)

Laboratory Biomarker Analysis OTHER

Correlative studies

Group 1 (avelumab and MHC class I up-regulation); Group 2 (avelumab, MHC class I up-regulation, T cells)

MCPyV TAg-specific Polyclonal Autologous CD8-positive T Cells BIOLOGICAL

Given IV

Group 2 (avelumab, MHC class I up-regulation, T cells)

Radiation Therapy RADIATION

Undergo radiation therapy

Also known as: Cancer Radiotherapy, Irradiate, Irradiated, irradiation, Radiation, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Group 1 (avelumab and MHC class I up-regulation); Group 2 (avelumab, MHC class I up-regulation, T cells)

Recombinant Interferon Beta BIOLOGICAL

Given via intra-tumor injection

Also known as: Beta Interferon, Betantrone, Feron, Human Interferon Beta, Interferon Beta, Interferon, Beta, Interferon-B, Interferon-beta, Naferon

Group 1 (avelumab and MHC class I up-regulation); Group 2 (avelumab, MHC class I up-regulation, T cells)

Eligibility Criteria

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

You may qualify if:

• Signed written informed consent
• Confirmation of MCC by internal pathology review of initial or subsequent biopsy or other pathologic material
• If an accessible lesion is present, a biopsy will be performed within 6 weeks of the start of study intervention; the results of the biopsy must be obtained prior to initiation of study intervention
• Evidence of MCPyV TAg tumor expression by immunohistochemistry on any prior or current tumor specimen or viral oncoprotein antibody confirmation within 6 weeks of the start of study intervention
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) =\< 2 at trial entry
• Patients must have at least one bi-dimensionally measurable lesion by palpation, clinical exam, or radiographic imaging within 6 weeks of the start of study intervention (X-ray, computed tomography \[CT\] scan, positron emission tomography \[PET\] scan, magnetic resonance imaging \[MRI\], or ultrasound)
• For patients designated to be treated on Group 2: cardiac ejection fraction \>= 35%; for patients with significant risk factors for coronary artery disease (Framingham risk score \> 15%), a cardiac stress test is recommended
• At least 3 weeks must have passed since any of the following: systemic corticosteroids, immunotherapy (for example, T-cell infusions, immunomodulatory agents, interleukins, MCC vaccines, intravenous immunoglobulin, expanded polyclonal tumor infiltrating lymphocytes \[TIL\] or lymphokine-activated killer \[LAK\] therapy), pentoxifylline, other small molecule or chemotherapy cancer treatment, other investigational agents or other systemic agents that target Merkel cell carcinoma

You may not qualify if:

• Known active infections or oral temperature \> 38.2 Celsius (C) fewer than 72 hours prior to receiving study treatment or systemic infection requiring chronic maintenance or suppressive therapy
• White blood cells (WBC) \< 200/mcl
• Hemoglobin (Hb) \< 8 g/dL
• Absolute neutrophil count (ANC) \< 1000/mcl
• Platelets \< 50,000/mcl
• New York Heart Association functional class III-IV heart failure, symptomatic pericardial effusion, stable or unstable angina, symptoms of coronary artery disease, congestive heart failure, clinically significant hypotension, or history of an ejection fraction of =\< 30 % (echocardiogram or multi gated acquisition scan \[MUGA\])
• Clinically significant pulmonary dysfunction, as determined by medical history and physical exam; patients so identified will undergo pulmonary functions testing and those with forced expiratory volume in 1 second (FEV1) \< 2.0 L or diffusion capacity of the lung for carbon monoxide (DLco) (corrected \[corr\] for hemoglobin \[Hgb\]) \< 50% will be excluded
• Creatinine clearance \< 30 ml/min which cannot be attributed to MCC metastasis
• Total bilirubin \> 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) \> 2.5 x ULN; for patients with liver metastases: AST/ALT \> 5 x ULN
• Active autoimmune disease (e.g. systemic lupus erythematosus, vasculitis, infiltrating lung disease, inflammatory bowel disease) whose possible progression during treatment would be considered unacceptable by the investigators
• Symptomatic and untreated central nervous system (CNS) metastasis; however, patients with 1 to 2 asymptomatic, less than 1 cm brain/CNS metastases without significant edema may be considered for treatment; if sub-centimeter CNS lesions are noted at study entry, then repeat imaging will be performed, if more than 4 weeks have elapsed from the last scan
• Any condition or organ toxicity that is deemed by the principal investigator (PI) or the attending physician to place the patient at unacceptable risk for treatment on the protocol
• Pregnant women, nursing mothers, men or women of reproductive ability who are unwilling to use effective contraception or abstinence; women of childbearing potential must have a negative pregnancy test within 2-6 weeks prior to treatment
• Clinically significant and ongoing immune suppression including, but not limited to, systemic immunosuppressive agents such as cyclosporine or corticosteroids, chronic lymphocytic leukemia (CLL), uncontrolled human immunodeficiency virus (HIV) infection, or solid organ transplantation

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• EMD Serono: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Carcinoma, Merkel Cell

Interventions

avelumab; Radiotherapy; Radiation; Interferon-beta

Condition Hierarchy (Ancestors)

Polyomavirus Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Therapeutics; Physical Phenomena; Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Dr. Aude Chapuis
• Organization: Fred Hutchinson Cancer Research Center

achapuis@fredhutch.org

2066674369

Study Officials

• Aude Chapuis

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: October 21, 2015
• First Posted: October 23, 2015
• Study Start: November 6, 2015
• Primary Completion: December 18, 2018
• Study Completion: December 18, 2018
• Last Updated: March 22, 2022
• Results First Posted: March 22, 2022

Record last verified: 2022-02

Locations

US (1)