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Leptomeningeal MetastasesPhase 1NCT03719768

Avelumab With Radiotherapy in Patients With Leptomeningeal Disease

A Phase 1 study testing Avelumab and Whole Brain Radiotherapy in people with Leptomeningeal Metastases and Leptomeningeal Disease, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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

Who is it for?
Ages 18 years and older
What is being tested?
Avelumab and Whole Brain Radiotherapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
1 siteUnited States
Study dates
10 Jun 2019to 21 Aug 2024
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 1. Histologically or cytologically confirmed diagnosis of any cancer except leukemia
  • 2. 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)
  • 3. Patients must have an Eastern Cooperative Oncology Group performance scale of < 3 OR Karnofsky Performance Status of >50.
  • 4. 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)
  • 5. An interval of at least 4 weeks following any surgical resection of brain lesions prior to treatment
  • 6. Be > 18 years of age on the day of signing consent
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  • 7. Demonstrate adequate organ function as defined in Table 2. All screening labs should be performed with 14 days of treatment initiation
  • 8. Resting baseline O2 saturation by pulse oximetry of > 92% at rest
  • 9. Patients must have recovered from the toxic effects of prior therapies (< Grade 1)
  • 10. Provision of signed and dated informed consent form
  • 11. Life expectancy of > 8 weeks
  • 12. Pregnancy test: negative serum or urine pregnancy test at screening for women of childbearing potential.
  • 13. 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.
  • 14. 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.
  • 15. Adequate Organ Function as defined per protocol

Who cannot join

  • 1. Receiving other treatments specifically administered to treat LMDz or antibody based therapies within the last 4 weeks. However, patients receiving concomitant non-cytotoxic therapy (hormonal or cytostatic therapy) to control systemic disease or bulk CNS disease will be eligible, provided the therapy is not a phase I agent, an agent which significantly penetrates the CSF (e.g., high-dose methotrexate, thiotepa, or high-dose ara-C), or an agent known to have serious unpredictable CNS side effects Except as listed in Inclusion Criteria #15 (above). Careful documentation of concurrently administered systemic drugs is required
  • 2. 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
  • 3. Unable or unwilling to have a contrast-enhanced brain MRI
  • 4. 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
  • 5. Patients on steroid therapy unless < 2 mg/day dexamethasone equivalents
  • 6. Prior chemotherapy or targeted small molecule therapy except as listed in Inclusion Criteria #15 and Exclusion #1(above) within 4 weeks prior to study Day 1 or nonrecovery (i.e., < Grade 1 or at baseline) from adverse events (AEs) due to agents administered > 4 weeks earlier
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  • 7. 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
  • 8. 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.
  • 9. Has evidence of active, non-infectious pneumonitis
  • 10. Has an active infection requiring systemic therapy
  • 11. 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
  • 12. Requires escalating or chronic supraphysiologic doses of corticosteroids (> 10 mg/day prednisone equivalents)
  • 13. 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
  • 14. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • 15. 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
  • 16. 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
  • 17. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1, 2 antibodies)
  • 18. Any test for hepatitis B (HBV) or hepatitis C virus (HCV) indicating acute or chronic infection
  • 19. Has received a live vaccine within 30 days prior to the first dose of trial treatment
  • 20. Prior administration of WBRT
  • 21. Known symptomatic brain metastases requiring steroids. Patients with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to study treatment, have discontinued corticosteroid treatment for these metastases for at least 4 weeks and are neurologically stable. Short courses of corticosteroids are permitted if these were started for leptomeningeal disease and can be tapered down to < 2 mg/day of dexamethasone equivalents and patients remain stable for 3 days prior to study treatment
  • 22. Known severe hypersensitivity reactions to monoclonal antibodies (Grade > 3) or any known history of anaphylaxis
  • 23. ORGAN TRANSPLANTATION: Prior organ transplantation including allogenic stem-cell transplantation
  • 24. CARDIOVASCULAR DISEASE: 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 (> New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication
  • 25. OTHER PERSISTING TOXICITIES: "Persisting toxicity related to prior therapy (NCI CTCAE v.5.0 Grade > 1); however, alopecia, sensory neuropathy Grade < 2, or other Grade < 2 not constituting a safety risk based on investigator's judgment are acceptable
  • 26. Other severe acute or chronic medical conditions, including immune colitis, inflammatory bowel disease, immune 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • H. Lee Moffitt Cancer Center and Research Institute

    Tampa, Florida, 33612

Other trials in United States

About this study

Official title: Phase IB Study of Avelumab With Radiotherapy in Patients With Leptomeningeal Disease

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

Being tested
Avelumab, Whole Brain Radiotherapy
Keywords
Whole Brain Radiotherapy, meningeal, LMDz, brain metastases, Immunotherapy
Medical subject headings
Meningeal Carcinomatosis, Meningeal Neoplasms, Brain Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AvelumabDrug

    Also called Bavencio

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

  • Whole Brain RadiotherapyRadiation

    Also called WBRT

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

Study groups in NCT03719768
Study groupRoleWhat they receive
Avelumab and Whole Brain RadiotherapyExperimentalAvelumab 800 mg intravenously (IV) and 3000 centriGray units (cGy) Whole Brain Radiotherapy once every 2 weeks
Receives: Drug: Avelumab; Radiation: Whole Brain Radiotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: End of treatment (3 months)

Secondary outcomes (2)

  1. Number of T Cells

    The number of T cells in the cerebrospinal fluid (CSF) and the CSF cytokine activation profile in the CSF (relative to serum) measured before and after Avelumab administration.

    Measured: Up to 11 months

  2. Activation Status of T Cells

    The activation status of T cells in the cerebrospinal fluid (CSF) and the CSF cytokine activation profile in the CSF (relative to serum) measured before and after Avelumab administration.

    Measured: Up to 11 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Oct 2018
  2. Study start10 Jun 2019
  3. Primary completion19 Jul 2022
  4. Study completion21 Aug 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03719768
Sponsor's protocol ID
MCC-19648
Other IDs
W1239387
Status last verified
Feb 2026
First submitted
23 Oct 2018
Last updated
2 Mar 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 40888040

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Avelumab and Whole Brain Radiotherapy in people with Leptomeningeal Metastases and Leptomeningeal Disease, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety and Dose Limiting Toxicity (DLT) measured by number of subjects with adverse events (AEs) (time frame: End of treatment (3 months)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03719768, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Mar 2026.

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