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Childhood AstrocytomaPhase 1NCT02444546

Wild-Type Reovirus in Combination With Sargramostim in Treating Younger Patients With High-Grade Relapsed or Refractory Brain Tumors

A Phase 1 study testing Laboratory Biomarker Analysis, Sargramostim and Wild-type Reovirus in people with Childhood Astrocytoma and Childhood Atypical Teratoid/Rhabdoid Tumor, run by Mayo Clinic 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
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Trial summary

This phase I trial studies the side effects and the best dose of wild-type reovirus (viral therapy) when given with sargramostim in treating younger patients with high grade brain tumors that have come back or that have not responded to standard therapy. Read more about this study

Who is it for?
Ages 10 to 21 years
What is being tested?
Laboratory Biomarker Analysis, Sargramostim and Wild-type Reovirus
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
1 siteUnited States
Study dates
21 Jun 2015to 21 Nov 2022
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 10 to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Histological confirmation of a high grade (grade 3 or 4) primary brain tumor either classified as a glioma (including astrocytoma, anaplastic oligodendroglioma and glioblastoma multiforme), medulloblastoma, atypical teratoid/rhabdoid tumor (AT/RT) or primitive neuroectodermal tumor (PNET)
  • Note: Patients with diffuse intrinsic pontine glioma (DIPG) are exempt from this confirmation of tumor if characteristic radiologic findings are noted on magnetic resonance imaging (MRI)
  • Patients must have no known curative therapy available
  • Evidence of tumor progression by MRI scan following radiation therapy or following the most recent anti-tumor therapy; note: patients who have had surgical treatment at recurrence are eligible if they had a resection with measurable residual disease on postoperative imaging or if there is imaging evidence of disease progression as compared to the first postoperative scan
  • Measurable disease: measurable by gadolinium MRI scan
  • Absolute neutrophil count (ANC) >= 750 /uL obtained =< 7 days prior to registration
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  • Absolute lymphocyte count (ALC) >= 250/uL obtained =< 7 days prior to registration
  • Platelet count (PLT) >= 75,000 /uL without transfusions obtained =< 7 days prior to registration
  • Hemoglobin >= 7.0 gm/dL obtained =< 7 days prior to registration
  • Total bilirubin =< 1.5 times upper limit of institutional normal (ULN) for age obtained =< 7 days prior to registration
  • Aspartate transaminase (AST) =< 3 times ULN for age obtained =< 7 days prior to registration
  • Serum albumin >= 2 g/dL
  • Creatinine =< 1.5 times ULN for age OR a creatinine clearance or glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2; obtained =< 7 days prior to registration
  • Karnofsky or Lansky performance status (PS): performance status of >= 50 assessed within two weeks prior to registration; neurological deficits in patients must have been relatively stable for a minimum of 1 week prior to study enrollment; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
  • Ability to understand and the willingness to provide written informed assent or consent
  • Willing to return to enrolling institution for follow-up
  • Immunosuppressants: patients must be receiving a stable or decreasing dose of dexamethasone for at least 1 week prior to start of therapy AND dexamethasone dose must be =< 0.1 mg/kg/day AND =< a total daily dose of 4 mg/day
  • If patient has a clinically indicated surgery or biopsy at any time during treatment with Reolysin, a tissue sample will be collected for correlative research purposes
  • Patient willing to provide mandatory blood samples for correlative research purposes; the inability to provide a blood sample or the lack of an available blood sample does not make the patient ineligible
  • Negative urine or serum pregnancy test done =< 7 days prior to registration for females who are post-menarchal
  • Patient agrees to use an acceptable form of contraception during the study and for up to 28 days after the last dose of Reolysin if patient or female partner is post-menarche; acceptable methods include 1) a double barrier method, such as condom and spermicide; 2) hormonal contraception methods, including pills, patches, rings, or injections except progestin-only containing pills (i.e., 'mini-pill'); 3) intrauterine device (non-progesterone T); 4) surgical methods such as a bilateral tubal ligation or a vasectomy; 5) abstinence
  • Must be able to avoid direct contact with pregnant women, infants < 3 months of age and immunocompromised individuals while on study and for >= 3 weeks following the last dose of study agent administration; direct contact is defined as household contact, i.e., anyone living with the patient
  • Life expectancy >= 3 months

Who cannot join

  • Fetal and newborn toxicity: any of the following
  • Pregnant women
  • Nursing women
  • Males or post-menarchal females who are unwilling to employ adequate contraception throughout the duration of the study and for at least 4 weeks after treatment has ended
  • Uncontrolled intercurrent illness including, but not limited to:
  • Ongoing or active infection, including localized infections
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  • Symptomatic congestive heart failure
  • Unstable angina pectoris or cardiac arrhythmia
  • Any psychiatric illness/social situations that would limit compliance with study requirements
  • Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • Known prior history of tuberculosis or positive purified protein derivative (PPD) test result
  • Known prior history of human immunodeficiency virus (HIV)
  • Administration of live vaccines =< 14 days prior to registration; note: patients may not receive any viral immunizations during the study and for 28 days after the last dose of Reolysin
  • Prior history of any viral-based therapy
  • Other concurrent chemotherapy, immunotherapy, radiotherapy, any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration [FDA]-approved indication and in the context of a research investigation) or receiving any other investigational agent which would be considered as a treatment for the primary neoplasm:
  • Chemotherapy =< 3 weeks of registration
  • Nitrosoureas or mitomycin C =< 6 weeks of registration
  • Small molecule cell cycle inhibitors =< 2 weeks prior to registration
  • Immunotherapy =< 6 weeks prior to registration
  • Monoclonal antibodies =< 3 half-lives prior to registration
  • Radiation therapy
  • Last fraction of craniospinal irradiation or total body irradiation =< 3 months prior to registration or last fraction of focal irradiation to symptomatic metastatic sites =< 4 weeks prior to registration
  • Growth factors
  • Colony forming growth factors < 2 weeks prior to registration (i.e., filgrastim, sargramostim, erythropoietin)
  • Neulasta < 2 weeks prior to registration
  • Failure to fully recover from acute, reversible effects of prior chemotherapy regardless of interval since last treatment

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Mayo Clinic

    Rochester, Minnesota, 55905

Other trials in United States

About this study

Official title: Phase 1 Study of Replication Competent Reovirus (Reolysin®) in Combination With GM-CSF in Pediatric Patients With Relapsed or Refractory Brain Tumors

This phase I trial studies the side effects and the best dose of wild-type reovirus (viral therapy) when given with sargramostim in treating younger patients with high grade brain tumors that have come back or that have not responded to standard therapy. A virus, called wild-type reovirus, which has been changed in a certain way, may be able to kill tumor cells without damaging normal cells. Sargramostim may increase the production of blood cells and may promote the tumor cell killing effects of wild-type reovirus. Giving wild-type reovirus together with sargramostim may kill more tumor cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To define the maximum tolerated dose (MTD) and describe the toxicities of wild-type reovirus (Reolysin) when given once a day for three days following two days of treatment with sargramostim (GM-CSF).

SECONDARY OBJECTIVES:

  1. To assess the safety, tolerability and adverse events in the patient population.

II. To assess the median overall survival time in this patient population. III. To assess the median progression free survival time in this patient population.

TERTIARY OBJECTIVES:

  1. To determine whether there is a correlation between antibody responsiveness to the virus and a positive tumor response to Reolysin in patients who receive the virus following treatment with GM-CSF.

II. To determine whether there is a correlation between an increased number of circulating monocytes and a positive tumor response to Reolysin in patients who receive the virus following treatment with GM-CSF.

III. To explore the possible predictive value of monocyte numbers in response to Reolysin + GM-CSF therapy.

OUTLINE: This is a dose-escalation study of wild-type reovirus.

Patients receive sargramostim subcutaneously (SC) daily on days 1 and 2 and wild-type reovirus intravenously (IV) over 60 minutes on days 3-5. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year, and then annually for up to 2 years.

Being tested
Laboratory Biomarker Analysis, Sargramostim, Wild-type Reovirus
Medical subject headings
Rhabdoid Tumor, Diffuse Intrinsic Pontine Glioma, Glioma, Oligodendroglioma, Astrocytoma, Medulloblastoma, Neuroectodermal Tumors, Primitive, Brain Neoplasms

What participants receive

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

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • SargramostimBiological

    Also called 23-L-Leucinecolony-Stimulating Factor 2, DRG-0012, Leukine, Prokine

    Given SC

  • Wild-type ReovirusBiological

    Also called Reolysin

    Given IV

Study groups in NCT02444546
Study groupRoleWhat they receive
Treatment (sargramostim, wild-type reovirus)ExperimentalPatients receive sargramostim SC daily on days 1 and 2 and wild-type reovirus IV over 60 minutes on days 3-5. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.
Receives: Other: Laboratory Biomarker Analysis; Biological: Sargramostim; Biological: Wild-type Reovirus

What is being measured

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

  1. MTD, based on the incidence of dose-limiting toxicity (DLT) assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.0

    MTD is the highest safely tolerated dose level where 1 of 6 patients experience DLT with the next higher dose having at least 2 patients out of a maximum of 6 patients experience DLT.

    Measured: Up to 84 days

Secondary outcomes (8)

  1. Adverse event profile

    The number and severity of adverse events (overall, by dose level, by treatment received) will be tabulated and summarized. The grade 3+ adverse events will also be described and summarized in a similar fashion.

    Measured: Up to 5 years

  2. Objective responses

    Objective responses will be summarized by descriptive summary statistics delineating complete and partial responses and stable and progressive disease.

    Measured: Up to 5 years

  3. Overall survival

    Will be summarized descriptively. Simple summary statistics will be supplemented with Kaplan-Meier survival estimates and relevant confidence intervals.

    Measured: Up to 5 years

  4. Time to progression

    Up to 5 years

    Measured: Will be summarized descriptively.

  5. Time to treatment failure

    Will be summarized descriptively. Time to treatment failure is defined as the time from registration to documentation of progression, unacceptable toxicity, or refusal to continue participation by the patient.

    Measured: Up to 5 years

  6. Time until any treatment-related toxicity

    Will be summarized descriptively.

    Measured: Up to 5 years

  7. Time until treatment-related grade 3+ toxicity

    Will be summarized descriptively.

    Measured: Up to 5 years

  8. Toxicity profile, assessed by CTCAE v4.0

    Toxicity is defined as adverse events that are classified as possibly, probably, or definitely related to study treatment. Overall toxicity incidence and toxicity profiles by dose level, patient, and treatment will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of the analysis.

    Measured: Up to 5 years

Timeline

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

  1. First posted14 May 2015 (estimated)
  2. Study start21 Jun 2015
  3. Primary completion13 Jul 2018
  4. Study completion21 Nov 2022

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
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02444546
Sponsor's protocol ID
MC1472
Other IDs
NCI-2015-00665, MC1472, P30CA015083
Status last verified
Apr 2023
First submitted
1 May 2015
Last updated
24 Apr 2023
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Laboratory Biomarker Analysis, Sargramostim and Wild-type Reovirus in people with Childhood Astrocytoma and Childhood Atypical Teratoid/Rhabdoid Tumor, run by Mayo Clinic 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 23 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 24 Apr 2023. 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?

MTD, based on the incidence of dose-limiting toxicity (DLT) assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.0 (time frame: Up to 84 days). 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 NCT02444546.

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 24 Apr 2023.

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