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Phase II Study of 177Lu-DOTATATE Radionuclide in Adults With Progressive or High-risk Meningioma

Primary Purpose

Meningioma

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Lutathera
Sponsored by
NYU Langone Health
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Meningioma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Male or female subjects aged ≥ 18 years.
  2. Karnofsky Performance Status ≥ 60.
  3. Histologically confirmed diagnosis WHO grade I-III meningioma:

    a. For grade I meningioma, subjects must have: i. Progressive disease after at least surgical resection and radiotherapy, as defined as an increase in size of the measurable primary lesion (bidirectional area) on imaging by 25% or more between scans separated by no more than 12 months.

    or ii. Progressive residual tumor after maximal safe resection, be located at or near critical organs at-risk and considered to be high-risk for radiation injury by the treating investigator. Prior external beam radiotherapy is not required for these subjects.

    b. For Grade II or III meningioma, subjects must have either: i. Progressive disease after at least surgical resection and radiotherapy, as defined as an increase in size of the measurable primary lesion (bi-directional area) on imaging by 25% or more between scans separated by no more than 12 months or ii. Residual measurable disease after surgery without requirement of progression.

  4. Positive 68Ga-DOTATATE uptake on PET-MRI.

    1. Positive uptake is defined as uptake higher than the background and SUV ratios adjusted to the liver and spleen uptake (adopted from Krenning score).
    2. 68Ga-DOTATATE uptake in target lesions should be Krenning score ≥ 2.
  5. Presence of measurable disease defined as at least one lesion measuring ≥10 mm in at least one dimension by contrast-enhanced MRI performed within 30 days prior to study registration.
  6. Multifocal disease is allowed but is limited to ≤ 3 measurable intracranial mass lesions on the most recent post-contrast MRI.
  7. Any neurological symptoms must be stable for at least 28 days prior to enrollment and patients should not require steroids to control neurological symptoms.
  8. There is no limit on the number of prior surgeries, radiation therapy, radiosurgery treatments or systemically administered therapeutic agents.
  9. For patients treated with external beam radiation, interstitial brachytherapy or radiosurgery, an interval ≥24 weeks must have elapsed from completion from these therapies to registration unless there is histopathologic confirmation of recurrent tumor or there is new enhancing tumor outside the radiation field (beyond the high dose region or the 80% isodose line).
  10. An interval of ≥28 days (or 5 half-lives, whichever is shorter) from prior cytotoxic chemotherapy (6 weeks from nitrosoureas), biologic agent, investigational agent or any other systemic agent prescribed for the purpose of treating meningioma.
  11. An interval of ≥28 days from craniotomy and ≥7 days from stereotactic biopsy.
  12. Availability of a paraffin-embedded archival tumor block from most recent tumor resection sufficient to generate at minimum 8 unstained slides but preferably up to 25 unstained slides; or, if a paraffin tumor block is unavailable, at minimum 8 unstained slides but preferably up to 25 unstained slides.

    a. Positive SSTR2 expression in the most recent tumor specimen must be confirmed by central pathology review.

  13. Patients must be willing and able to undergo regular MRI scans of the brain.
  14. Patients must have recovered to CTCAE grade ≤1 or pretreatment baseline from clinically significant adverse events related to prior therapy (exclusions include alopecia, laboratory values listed per inclusion criteria, lymphopenia, sensory neuropathy ≤ grade 2, or other ≤ grade 2 not constituting a safety risk based on the investigator's judgment).
  15. Adequate organ and bone marrow function as defined below (within 21 days of treatment initiation):

    1. White blood cell (WBC) ≥ 2,000/mm3
    2. Absolute neutrophil count (ANC) ≥ 1,000/mm3
    3. Platelet count ≥ 75,000/mm3
    4. Hemoglobin ≥ 8 gm/dL
    5. AST(SGOT)/ALT(SGPT) ≤ 3 x laboratory upper limit of normal (ULN)
    6. Creatinine clearance (measured or calculated) ≥ 50 mL/min OR creatinine levels > 150 μMol/L (1.7 mg/dL)
    7. Total serum bilirubin ≤ 3 X ULN (except participants with Gilbert's Syndrome, who can have a total bilirubin ≤ 5 X ULN)
    8. Serum albumin level of more than 3.0 g/dL, unless the prothrombin time value was within the normal range
  16. Women of childbearing potential (WOCBP) and men able to father a child must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in the study, she must inform her treating physician immediately.
  17. Able to understand and willing to sign an IRB approved written informed consent document.

Exclusion Criteria

  1. Patients with a clinical diagnosis of NF2 (either by NIH or Manchester criteria) or with a molecular diagnosis of NF2.
  2. Patients with radiation-associated meningiomas.
  3. Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm. This includes treatment with Somatostatin LAR within 4 weeks prior to treatment, or any patient receiving treatment with short-acting Octreotide that cannot be interrupted for greater than 24 hours before treatment.
  4. Peptide receptor radionuclide therapy at any time prior to registration.
  5. Known hypersensitivity to somatostatin analogues or any component of the 68Ga- DOTATATE or 177Lu-DOTATATE formulations.
  6. Known additional malignancy that is progressing or requires active treatment within 2 years of start of study drug. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and in situ cervical cancer that has undergone potentially curative therapy.
  7. Current or planned participation in another study of an investigational agent or investigational device.
  8. Active infection requiring intravenous therapy with antibiotics.
  9. Uncontrolled intercurrent illness including, but not limited to, clinically significant (i.e. active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), congestive heart failure (≥ NYHA class II), unstable angina pectoris, or serious cardiac arrhythmia requiring medication.
  10. Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
  11. Active Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test is positive).
  12. Other severe acute or chronic medical or psychiatric conditions (within the past year) including recent or active suicidal ideation or behavior, or laboratory abnormalities that may increase the risk associated with study participation or treatment on study or may interfere with the interpretation of study results.
  13. Pregnant and/or breastfeeding patients. Women of childbearing potential (WOCBP) must have a negative pregnancy test within 14 days of study entry.

Sites / Locations

  • NYU Langone HealthRecruiting
  • Cleveland ClinicRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Lutathera

Arm Description

Outcomes

Primary Outcome Measures

Progression Free Survival at 6 months (PFS-6)
proportion of subjects who achieve a complete response (CR), partial response (PR), or stable disease (SD) at 6 months from start of Lutathera treatment. Radiographic treatment response will be assessed by measuring the bidirectional tumor diameters on contrast-enhanced MRI in patients who received at least one dose of Lutathera compared to baseline measurements at time of study enrollment

Secondary Outcome Measures

Objective Response Rate (ORR)
defined as the best response [Complete Response (CR) + Partial Response (PR) + stable disease (SD)] recorded from the start of the study until the end of study in patients who received at least one dose of Lutathera.
Overall Survival at 12 months (OS-12)
proportion of subjects who are alive at 12 months from start of Lutathera treatment. Survival data will be captured by clinical follow-up every 8 weeks during treatment with Lutathera and by follow-up phone calls every 12 weeks for up to 2 years after completion of treatment with Lutathera.
Progression Free Survival (PFS)
defined as the number of days from the treatment start date to the date of documented disease progression or death due to any cause.
Overall Survival (OS)
defined as the number of days from the treatment start date to the date of death due to any cause.

Full Information

First Posted
May 30, 2019
Last Updated
August 3, 2023
Sponsor
NYU Langone Health
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1. Study Identification

Unique Protocol Identification Number
NCT03971461
Brief Title
Phase II Study of 177Lu-DOTATATE Radionuclide in Adults With Progressive or High-risk Meningioma
Official Title
A Single Arm, Open-label, Multicenter Phase II Study of 177Lu-DOTATATE Radionuclide in Adults With Progressive or High-risk Meningioma
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 15, 2019 (Actual)
Primary Completion Date
May 2024 (Anticipated)
Study Completion Date
May 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NYU Langone Health

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This single arm, open-label study will evaluate the efficacy of Lutathera (177Lu-DOTATATE) administered intravenously every 8 weeks for a total of 4 doses in patients with progressive WHO I-III or residual high-risk Ga-DOTATATE PET-MRI positive meningioma. Ga-DOTATATE PET-MRI scans will be obtained prior to initiation of Lutathera treatment and 6 months after the initiation of Lutathera treatment. The latter will be performed within the 14 days prior to the last dose of Lutathera treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Meningioma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Open-label, single arm, multicenter, two-stage phase 2 clinical study.
Masking
None (Open Label)
Allocation
N/A
Enrollment
32 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Lutathera
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Lutathera
Other Intervention Name(s)
177Lu-DOTATATE
Intervention Description
administered intravenously every 8 weeks for a total of 4 doses
Primary Outcome Measure Information:
Title
Progression Free Survival at 6 months (PFS-6)
Description
proportion of subjects who achieve a complete response (CR), partial response (PR), or stable disease (SD) at 6 months from start of Lutathera treatment. Radiographic treatment response will be assessed by measuring the bidirectional tumor diameters on contrast-enhanced MRI in patients who received at least one dose of Lutathera compared to baseline measurements at time of study enrollment
Time Frame
6 Months
Secondary Outcome Measure Information:
Title
Objective Response Rate (ORR)
Description
defined as the best response [Complete Response (CR) + Partial Response (PR) + stable disease (SD)] recorded from the start of the study until the end of study in patients who received at least one dose of Lutathera.
Time Frame
12 months
Title
Overall Survival at 12 months (OS-12)
Description
proportion of subjects who are alive at 12 months from start of Lutathera treatment. Survival data will be captured by clinical follow-up every 8 weeks during treatment with Lutathera and by follow-up phone calls every 12 weeks for up to 2 years after completion of treatment with Lutathera.
Time Frame
12 months
Title
Progression Free Survival (PFS)
Description
defined as the number of days from the treatment start date to the date of documented disease progression or death due to any cause.
Time Frame
2 Years Post Treatment
Title
Overall Survival (OS)
Description
defined as the number of days from the treatment start date to the date of death due to any cause.
Time Frame
2 Years Post Treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female subjects aged ≥ 18 years. Karnofsky Performance Status ≥ 60. Histologically confirmed diagnosis WHO grade I-III meningioma: a. For grade I meningioma, subjects must have: i. Progressive disease after at least surgical resection and radiotherapy, as defined as an increase in size of the measurable primary lesion (bidirectional area) on imaging by 25% or more between scans separated by no more than 12 months. or ii. Progressive residual tumor after maximal safe resection, be located at or near critical organs at-risk and considered to be high-risk for radiation injury by the treating investigator. Prior external beam radiotherapy is not required for these subjects. b. For Grade II or III meningioma, subjects must have either: i. Progressive disease after at least surgical resection and radiotherapy, as defined as an increase in size of the measurable primary lesion (bi-directional area) on imaging by 25% or more between scans separated by no more than 12 months or ii. Residual measurable disease after surgery without requirement of progression. Positive 68Ga-DOTATATE uptake on PET-MRI. Positive uptake is defined as uptake higher than the background and SUV ratios adjusted to the liver and spleen uptake (adopted from Krenning score). 68Ga-DOTATATE uptake in target lesions should be Krenning score ≥ 2. Presence of measurable disease defined as at least one lesion measuring ≥10 mm in at least one dimension by contrast-enhanced MRI performed within 30 days prior to study registration. Multifocal disease is allowed but is limited to ≤ 3 measurable intracranial mass lesions on the most recent post-contrast MRI. Any neurological symptoms must be stable for at least 28 days prior to enrollment and patients should not require steroids to control neurological symptoms. There is no limit on the number of prior surgeries, radiation therapy, radiosurgery treatments or systemically administered therapeutic agents. For patients treated with external beam radiation, interstitial brachytherapy or radiosurgery, an interval ≥24 weeks must have elapsed from completion from these therapies to registration unless there is histopathologic confirmation of recurrent tumor or there is new enhancing tumor outside the radiation field (beyond the high dose region or the 80% isodose line). An interval of ≥28 days (or 5 half-lives, whichever is shorter) from prior cytotoxic chemotherapy (6 weeks from nitrosoureas), biologic agent, investigational agent or any other systemic agent prescribed for the purpose of treating meningioma. An interval of ≥28 days from craniotomy and ≥7 days from stereotactic biopsy. Availability of a paraffin-embedded archival tumor block from most recent tumor resection sufficient to generate at minimum 8 unstained slides but preferably up to 25 unstained slides; or, if a paraffin tumor block is unavailable, at minimum 8 unstained slides but preferably up to 25 unstained slides. a. Positive SSTR2 expression in the most recent tumor specimen must be confirmed by central pathology review. Patients must be willing and able to undergo regular MRI scans of the brain. Patients must have recovered to CTCAE grade ≤1 or pretreatment baseline from clinically significant adverse events related to prior therapy (exclusions include alopecia, laboratory values listed per inclusion criteria, lymphopenia, sensory neuropathy ≤ grade 2, or other ≤ grade 2 not constituting a safety risk based on the investigator's judgment). Adequate organ and bone marrow function as defined below (within 21 days of treatment initiation): White blood cell (WBC) ≥ 2,000/mm3 Absolute neutrophil count (ANC) ≥ 1,000/mm3 Platelet count ≥ 75,000/mm3 Hemoglobin ≥ 8 gm/dL AST(SGOT)/ALT(SGPT) ≤ 3 x laboratory upper limit of normal (ULN) Creatinine clearance (measured or calculated) ≥ 50 mL/min OR creatinine levels > 150 μMol/L (1.7 mg/dL) Total serum bilirubin ≤ 3 X ULN (except participants with Gilbert's Syndrome, who can have a total bilirubin ≤ 5 X ULN) Serum albumin level of more than 3.0 g/dL, unless the prothrombin time value was within the normal range Women of childbearing potential (WOCBP) and men able to father a child must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in the study, she must inform her treating physician immediately. Able to understand and willing to sign an IRB approved written informed consent document. Exclusion Criteria Patients with a clinical diagnosis of NF2 (either by NIH or Manchester criteria) or with a molecular diagnosis of NF2. Patients with radiation-associated meningiomas. Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm. This includes treatment with Somatostatin LAR within 4 weeks prior to treatment, or any patient receiving treatment with short-acting Octreotide that cannot be interrupted for greater than 24 hours before treatment. Peptide receptor radionuclide therapy at any time prior to registration. Known hypersensitivity to somatostatin analogues or any component of the 68Ga- DOTATATE or 177Lu-DOTATATE formulations. Known additional malignancy that is progressing or requires active treatment within 2 years of start of study drug. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and in situ cervical cancer that has undergone potentially curative therapy. Current or planned participation in another study of an investigational agent or investigational device. Active infection requiring intravenous therapy with antibiotics. Uncontrolled intercurrent illness including, but not limited to, clinically significant (i.e. active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), congestive heart failure (≥ NYHA class II), unstable angina pectoris, or serious cardiac arrhythmia requiring medication. Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). Active Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test is positive). Other severe acute or chronic medical or psychiatric conditions (within the past year) including recent or active suicidal ideation or behavior, or laboratory abnormalities that may increase the risk associated with study participation or treatment on study or may interfere with the interpretation of study results. Pregnant and/or breastfeeding patients. Women of childbearing potential (WOCBP) must have a negative pregnancy test within 14 days of study entry.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Rebecca Rastall, RN, BSc, MSc
Phone
(212) 263-3668
Email
Rebecca.Rastall@nyulangone.org
First Name & Middle Initial & Last Name or Official Title & Degree
Erika Waalkes
Email
Erika.Waalkes@nyulangone.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Erik Sulman, MD
Organizational Affiliation
New York Langone Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
NYU Langone Health
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Vivian Chan
Phone
212-263-4436
Email
Vivian.Chan@nyulangone.org
First Name & Middle Initial & Last Name & Degree
Erik Sulman, MD
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David Peereboom, MD
Email
PEEREBD@ccf.org
First Name & Middle Initial & Last Name & Degree
David Peereboom, MD

12. IPD Sharing Statement

Learn more about this trial

Phase II Study of 177Lu-DOTATATE Radionuclide in Adults With Progressive or High-risk Meningioma

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