Stereotactic Body Radiation Therapy and Avelumab Immunotherapy for Treatment of Malignant Mesothelioma

NCT03399552 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 17-358
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 7

Brief Summary

The purpose of this study is to find out whether the combination of avelumab and SBRT is safe and what effect avelumab has on mesothelioma when given in combination with SBRT. In addition, a goal of this protocol is to study the effect of radiation therapy on the immune system. It is thought that radiation treatment may create a form of 'vaccine' against cancer inside the body and immunotherapy may improve this effect. The combination of radiation treatment and immunotherapy may be more effective against cancer than either radiation or immunotherapy alone.

Conditions

Malignant Mesothelioma (MPM)

Keywords

Stereotactic Body Radiation Therapy; Avelumab Immunotherapy; 17-358

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  defined by modified RECIST 1.1 for mesothelioma

  3 years

Study Arms (1)

Avelumab

EXPERIMENTAL

The treatment will consist of one dose of avelumab every other week as well as a short course of SBRT after the first two doses of avelumab.

Drug: Avelumab; Radiation: Stereotactic Body Radiation Therapy

Interventions

Avelumab DRUG

10mg/kg delivered by IV infusion

Avelumab

Stereotactic Body Radiation Therapy RADIATION

short course of SBRT after the first two doses of avelumab

Avelumab

Eligibility Criteria

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

You may qualify if:

• Patient willing and able to provide written informed consent for the trial.
• Patient age ≥ 18 at time of consent.
• Histologically or cytologically confirmed malignant pleural or peritoneal mesothelioma (MPM).
• No plans for surgical resection.
• At least one prior line of systemic therapy. Note: Patients on prior immunotherapy are eligible.
• At least one targetable lesion appropriate for palliative SBRT and one non-target lesion
• Karnofsky Performance Score (KPS) ≥ 70%
• If of childbearing potential, must be willing to use highly effective mode of contraception for at least one month prior, during, and for 2 months after the end of active therapy
• Adequate organ function, defined as:
• Absolute Neutrophil Count ≥ 1.5K/mcL.
• Platelet count ≥ 100K/mcL.
• Adequate renal function as defined by an estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula or serum creatinine ≤ 1.5 x ULN
• Hemoglobin \> 9g/dL (prior transfusion permitted)
• Total bilirubin level ≤ 1.5 × the upper limit of normal (ULN) range
• AST and ALT levels ≤ 2.5 × ULN or AST and ALT levels ≤ 5 x ULN (for subjects with documented metastatic disease to the liver).

You may not qualify if:

• Currently participating and receiving another study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
• Prior radiation therapy precluding SBRT
• Continuous oxygen use
• Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
• Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible. Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
• 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 ≥ 3)
• Patient who rapidly progressed on prior immunotherapy, as determined by the treating physician, are not eligible.
• Prior Therapies:
• Treatment with a monoclonal antibody within 4 weeks prior to study Day 1 or has not recovered (i.e., ≥ Grade 1 at baseline) from adverse events due to agents administered
• Prior chemotherapy, targeted small molecule therapy, within 4 weeks prior to study Day 1 or has not recovered (i.e., ≥ Grade 1 at baseline) from adverse events due to a previously administered agent (excluding Grade 2 neuropathy).
• Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti- Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways) within 4 weeks prior to study Day 1 or has not recovered (i.e., \>/= Grade 1 at baseline) from adverse events
• Comorbidities or Prior Conditions:
• Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Prior organ transplantation including allogenic stem-cell transplantation.
• Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Pfizer: collaborator

Study Sites (7)

Memorial Sloan Kettering at Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Rockville Centre

Rockville Centre, New York, 11570, United States

Location

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Mesothelioma, Malignant

Interventions

avelumab; Radiosurgery

Condition Hierarchy (Ancestors)

Mesothelioma; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: Dr. Andreas Rimner, MD
• Organization: Memorial Sloan Kettering Cancer Center

Rimnera@MSKCC.ORG

646-608-2449

Study Officials

• Andreas Rimner, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a single-arm, two-stage study that will be conducted at Memorial Sloan Kettering Cancer Center Main Campus and regional sites.

Study Record Dates

• First Submitted: January 9, 2018
• First Posted: January 16, 2018
• Study Start: December 20, 2017
• Primary Completion: January 20, 2023
• Study Completion: January 20, 2023
• Last Updated: October 23, 2023
• Results First Posted: October 23, 2023

Record last verified: 2023-01

Locations

US (7)