Clinical Trials /

A Longitudinal Assessment of Tumor Evolution in Patients With Brain Cancer

NCT03425292

Description:

The purpose of this study is to test the safety and tolerability of the research study drugs nivolumab, ipilimumab, and bevacizumab when used following surgery and before standard therapy with radiation and temozolomide in patients with newly diagnosed high grade glioma. Additional aims of the study are to: - Find out side effects (good and bad) of nivolumab and ipilimumab with/without bevacizumab and/or temozolomide. - Evaluate any preliminary evidence of anticancer activity of nivolumab and ipilimumab with/without bevacizumab and/or temozolomide. - Evaluate tumor characteristics by collecting brain tumor tissue samples. - Measure the amount of nivolumab and ipilimumab in biospecimens. - Look at biomarkers in biospecimens.

Related Conditions:
  • Malignant Glioma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Longitudinal Assessment of Tumor Evolution in Patients With Brain Cancer
  • Official Title: A Longitudinal Assessment of Tumor Evolution in Patients With Brain Cancer

Clinical Trial IDs

  • ORG STUDY ID: JWCI-17-0801
  • NCT ID: NCT03425292

Conditions

  • Newly Diagnosed High Grade Glioma

Interventions

DrugSynonymsArms
Temozolomidetemodar1 SOC
Nivolumabopdivo2 Nivo
Ipilimumabyervoy3 Nivo-Ipi
Bevacizumabavastin4 Nivo-Ipi-Bev
Metronomic Temozolomidetemodar5 Nivo-Ipi-TMZ

Purpose

The purpose of this study is to test the safety and tolerability of the research study drugs nivolumab, ipilimumab, and bevacizumab when used following surgery and before standard therapy with radiation and temozolomide in patients with newly diagnosed high grade glioma. Additional aims of the study are to: - Find out side effects (good and bad) of nivolumab and ipilimumab with/without bevacizumab and/or temozolomide. - Evaluate any preliminary evidence of anticancer activity of nivolumab and ipilimumab with/without bevacizumab and/or temozolomide. - Evaluate tumor characteristics by collecting brain tumor tissue samples. - Measure the amount of nivolumab and ipilimumab in biospecimens. - Look at biomarkers in biospecimens.

Detailed Description

      Patients having a clinically planned surgical procedure (biopsy or cytoreduction) for a
      suspected diagnosis of high grade glioma will be approached for participation in this study.
      Tumor tissue obtained from surgery will be used for histological diagnosis and clinical
      molecular profiling, and excess tumor tissue will be collected for potential correlative
      studies. A small sample of blood and CSF for research will also be collected.

      Once a diagnosis of high grade glioma is confirmed, the patient will be allocated to either
      Treatment Arm 1 standard of care (radiation + chemotherapy), Treatment Arm 2 (nivolumab),
      Treatment Arm 3 (nivolumab + ipilimumab), Treatment Arm 4 (nivolumab + ipilimumab +
      bevacizumab), or Treatment Arm 5 (nivolumab + ipilimumab + temozolomide), or Treatment Arm 6
      (nivolumab + ipilimumab + bevacizumab+ temozolomide). Treatment will be started approximately
      7-42 days following surgery once the patient has recovered from surgery. Routine clinical
      evaluations will be performed prior to treatment initiation and throughout treatment as
      clinically indicated. Radiographic brain imaging will be performed approximately 21-42 after
      treatment initiation and then routinely for medical management. Tumor response will be
      assessed according to immunotherapy Response Assessment in Neuro-Oncology (iRANO) Working
      Group criteria.

      Treatment may continue until the patient experiences unacceptable toxicity or clear disease
      progression. The determination of whether to stop treatment due to disease progression will
      be based on the investigator's evaluation of the patient's clinical and radiographic
      condition, taking into consideration the interpretation of localized inflammatory responses
      that can mimic radiographic features of tumor progress. Patients discontinuing treatment will
      be directed by their treating physician for the next step in their medical management - such
      as a clinically-indicated cytoreductive surgery, standard radiation chemotherapy if not
      assigned to study arm 1, or a different treatment regimen. If another treatment is started,
      clinical evaluations and response assessments will continue as clinically-indicated; blood
      and CSF will be collected after the first month, then every three to six months.
    

Trial Arms

NameTypeDescriptionInterventions
1 SOCActive ComparatorStandard conformal brain radiation therapy with concurrent and adjuvant temozolomide
  • Temozolomide
2 NivoExperimentalNivolumab
  • Nivolumab
3 Nivo-IpiExperimentalNivolumab plus Ipilimumab
  • Nivolumab
  • Ipilimumab
4 Nivo-Ipi-BevExperimentalNivolumab plus Ipilimumab plus Bevacizumab
  • Nivolumab
  • Ipilimumab
  • Bevacizumab
5 Nivo-Ipi-TMZExperimentalNivolumab plus Ipilimumab plus metronomic Temozolomide
  • Nivolumab
  • Ipilimumab
  • Metronomic Temozolomide
6 Nivo-Ipi-Bev-TMZExperimentalNivolumab plus Ipilimumab plus Bevacizumab plus metronomic Temozolomide
  • Nivolumab
  • Ipilimumab
  • Bevacizumab
  • Metronomic Temozolomide

Eligibility Criteria

        Inclusion Criteria:

          1. Participant has the ability to understand and the willingness to provide a signed and
             dated informed consent form.

          2. Participant has the willingness to comply with all study procedures and availability
             for the duration of the study.

          3. Participant is being evaluated for a potential, or known, diagnosis of high grade
             glioma.

          4. Participant is a candidate for brain surgery.

          5. Participant is male or female, ≥ 18 years of age.

          6. Participant has a Karnofsky Performance Status ≥ 60%:

        Exclusion Criteria:

          1. Participant has received prior anti-cancer treatment for high grade glioma.

          2. Participant has a diagnosis of immunodeficiency or active autoimmune disease.

          3. Participant is receiving chronic systemic steroid therapy in dosing exceeding 8 mg
             daily of dexamethasone equivalent or any other form of immunosuppressive therapy
             within 7 days prior to the first dose of study drug. Note: This is assessed after
             surgery, prior to starting drug treatment.

          4. Participant has received a live vaccine within 28 days prior to the first dose of
             study agent. Examples of live vaccines include, but are not limited to measles, mumps,
             rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus
             Calmette-Guérin (BCG), typhoid vaccine, and intranasal influenza vaccines (e.g.,
             FluMist®).

          5. Participant has a severe or uncontrolled medical disorder that would, in the
             investigator's opinion, impair ability to receive study intervention (i.e.,
             uncontrolled diabetes, chronic renal disease, chronic pulmonary disease or active,
             uncontrolled infection, psychiatric illness/social situations that would limit
             compliance with study requirements).

          6. Participant is a female of childbearing potential who is pregnant or nursing.

          7. Participant has a history of thrombotic or hemorrhagic stroke or myocardial infarction
             within 6 months.

          8. Participant has a history of intestinal perforations, fistula, hemorrhages, and/or
             hemoptysis ≤ 6 months prior to first study treatment.

          9. Participant has active gastrointestinal bleeding.

         10. Participant has uncontrolled hypertension (systolic blood pressure ≥ 160 mm Hg and/or
             diastolic blood pressure ≥ 90 mm Hg).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Rate of dose limiting toxicities
Time Frame:first 28 days of treatment
Safety Issue:
Description:treatment-related adverse events that impact administration of treatment

Secondary Outcome Measures

Measure:Treatment-related adverse events
Time Frame:approximately 7 months
Safety Issue:
Description:Toxicity will be assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 4.03.
Measure:Tumor response rates
Time Frame:up to 5 years
Safety Issue:
Description:Evidence of anti-tumor activity as measured according to immunotherapy Response Assessment in Neuro-Oncology (iRANO) criteria.
Measure:Progression free survival (PFS)
Time Frame:up to 5 years
Safety Issue:
Description:The duration of time from start of treatment until objective tumor response.
Measure:Overall survival (OS)
Time Frame:up to 5 years
Safety Issue:
Description:The duration of time from start of treatment to death.
Measure:Levels of immunotherapeutic agents in specimens
Time Frame:approximately 4 months
Safety Issue:
Description:Immunotherapeutic drug levels in specimens.
Measure:Change in clinical molecular profile of tumor tissue after treatment
Time Frame:approximately 6 months to 1 year
Safety Issue:
Description:Comparison of tumor tissue molecular profile generated from before and after study treatment.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:John Wayne Cancer Institute

Trial Keywords

  • immunotherapy
  • nivolumab
  • ipilimumab
  • bevcizumab
  • temozolomide

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