Avelumab With Radiotherapy in Patients With Leptomeningeal Disease

NCT03719768 | Completed Phase 1 FDA Drug

• 2 other identifiers: MCC-19648W1239387
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This study is to find a safe dose of the combination of Avelumab and Whole Brain Radiotherapy (WBRT) in patients with Leptomeningeal Disease.

Conditions

Leptomeningeal Metastases; Leptomeningeal Disease

Keywords

Whole Brain Radiotherapy; meningeal; LMDz; brain metastases; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Safety and Dose Limiting Toxicity (DLT) measured by number of subjects with adverse events (AEs)

  Adverse events will only include those that are determined to be related to study drug. A DLT will be defined as any one of the following adverse events occurring within 28 days from first dose of Avelumab. Central Nervous System (CNS) toxicities: Any grade 3 or higher central nervous adverse events, including but not limited to cerebral hemorrhage and new-onset neurologic deficit. Non-CNS toxicities: Any grade 3 or higher nonhematologic AE with the exception of alopecia and fatigue - Grade \> 3 nausea, vomiting, or diarrhea despite maximal medical therapy - Grade \> 3 laboratory value if 1)medical intervention is required to treat the patient or 2) the abnormality leads to hospitalization • Any grade 3 or 4 event that does not improve within 6 weeks

  End of treatment (3 months)

Secondary Outcomes (2)

• Number of T Cells

  Up to 11 months

• Activation Status of T Cells

  Up to 11 months

Other Outcomes (1)

• Overall Survival (OS) Rate at 3 months

  3 months

Study Arms (1)

Avelumab and Whole Brain Radiotherapy

EXPERIMENTAL

Avelumab 800 mg intravenously (IV) and 3000 centriGray units (cGy) Whole Brain Radiotherapy once every 2 weeks

Drug: Avelumab; Radiation: Whole Brain Radiotherapy

Interventions

Avelumab DRUG

Patients will be given 800 mg Avelumab as a one hour intravenous infusion once every 2 weeks.

Also known as: Bavencio

Avelumab and Whole Brain Radiotherapy

Whole Brain Radiotherapy RADIATION

Patients will be given 3000 cGy Whole Brain Radiotherapy once every 2 weeks

Also known as: WBRT

Avelumab and Whole Brain Radiotherapy

Eligibility Criteria

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

You may qualify if:

• \. Histologically or cytologically confirmed diagnosis of any cancer except leukemia
• \. Patients must have the presence of malignant cells in the CSF (CSF+) OR at least 2 of the 3 following features: 1) clinical signs and symptoms of LMDz 2) characteristic radiographic abnormalities , and 3) "suspicious" CSF (Chamberlain 2017)
• \. Patients must have an Eastern Cooperative Oncology Group performance scale of \< 3 OR Karnofsky Performance Status of \>50.
• \. An interval of at least 2 weeks after the end of prior radiation therapy to the brain (e.g., stereotactic radiosurgery or other-WBRT is excluded)
• \. An interval of at least 4 weeks following any surgical resection of brain lesions prior to treatment
• \. Be \> 18 years of age on the day of signing consent
• \. Demonstrate adequate organ function as defined in Table 2. All screening labs should be performed with 14 days of treatment initiation
• \. Resting baseline O2 saturation by pulse oximetry of \> 92% at rest
• \. Patients must have recovered from the toxic effects of prior therapies (\< Grade 1)
• \. Provision of signed and dated informed consent form
• \. Life expectancy of \> 8 weeks
• \. Pregnancy test: negative serum or urine pregnancy test at screening for women of childbearing potential.
• \. Contraception: Highly effective contraception for both male and female subjects throughout the study and for at least 30 days after last Avelumab treatment administration, if the risk of conception exists.
• \. If the disease has progressed on current treatment in the CNS prior to consent, patients may continue Her 2 directed antibody treatment (trastuzumab and pertuzumab), aromatase inhibitor or tamoxifen while on the study; patients with triple negative breast cancer may continue capecitabine, eribulin or paclitaxel while on the study per PI discretion.
• \. Adequate Organ Function as defined per protocol

You may not qualify if:

• \. Patients with a ventriculoperitoneal or ventriculoatrial shunt must have an on/off device in their shunt systems to be eligible for the study. Patients must be able to tolerate shunt closure for \~4 hours without development of clinical signs of increased intracranial pressure. Patients unable to tolerate shunt closure for \~4 hours will not be eligible for the study
• \. Unable or unwilling to have a contrast-enhanced brain MRI
• \. Currently participating in or having participated in a study of an investigational agent or device \< 4 weeks prior to the first dose of study treatment
• \. Patients on steroid therapy unless \< 2 mg/day dexamethasone equivalents
• \. 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
• \. Has an active autoimmune disease requiring systemic treatment within the past 3 months (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive agents) or has a diagnosis of immunodeficiency. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study. Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• \. Has evidence of active, non-infectious pneumonitis
• \. Has an active infection requiring systemic therapy
• \. Had major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to day 1 of treatment on study. Ommaya placement is allowed
• \. Requires escalating or chronic supraphysiologic doses of corticosteroids (\> 10 mg/day prednisone equivalents)
• \. Has a history of current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
• \. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• \. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 90 days after the last dose of trial treatment
• \. Has received 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 6 months before the beginning of study treatment
• \. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1, 2 antibodies)

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Pfizer: collaborator

Study Sites (1)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Related Publications (1)

• Pina Y, Law V, Sahebjam S, Tran N, Siddarajappa N, Li J, Mo Q, Phadke MS, Arrington J, Macaulay R, Mokhtari S, Evernden B, Ahmed KA, Smalley I, Yu M, Smalley KSM, Forsyth PA. Phase IB study of Avelumab and whole brain radiotherapy in patients with leptomeningeal disease from solid tumors: Results and molecular analyses. Neuro Oncol. 2025 Dec 1;27(12):3237-3249. doi: 10.1093/neuonc/noaf183.

  PMID: 40888040 DERIVED

Related Links

• Moffitt Cancer Center Clinical Trials Website

MeSH Terms

Conditions

Meningeal Carcinomatosis; Meningeal Neoplasms; Brain Neoplasms

Interventions

avelumab

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Brain Diseases; Central Nervous System Diseases

Study Officials

• Peter A Forsyth, MD

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: October 23, 2018
• First Posted: October 25, 2018
• Study Start: June 10, 2019
• Primary Completion: July 19, 2022
• Study Completion: August 21, 2024
• Last Updated: March 2, 2026

Record last verified: 2026-02

Locations

US (1)