Clinical Trials /

Testing the Addition of the Immune Therapy Drugs, Tocilizumab and Atezolizumab, to Radiation Therapy for Recurrent Glioblastoma

NCT04729959

Description:

This phase II trial studies the best dose and effect of tocilizumab in combination with atezolizumab and stereotactic radiation therapy in treating glioblastoma patients whose tumor has come back after initial treatment (recurrent). Tocilizumab is a monoclonal antibody that binds to receptors for a protein called interleukin-6 (IL-6), which is made by white blood cells and other cells in the body as well as certain types of cancer. This may help lower the body's immune response and reduce inflammation. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Fractionated stereotactic radiation therapy uses special equipment to precisely deliver multiple, smaller doses of radiation spread over several treatment sessions to the tumor. The goal of this study is to change a tumor that is unresponsive to cancer therapy into a more responsive one. Therapy with fractionated stereotactic radiotherapy in combination with tocilizumab may suppress the inhibitory effect of immune cells surrounding the tumor and consequently allow an immunotherapy treatment by atezolizumab to activate the immune response against the tumor. Combination therapy with tocilizumab, atezolizumab and fractionated stereotactic radiation therapy may shrink or stabilize the cancer better than radiation therapy alone in patients with recurrent glioblastoma.

Related Conditions:
  • Diffuse Astrocytoma
  • Glioblastoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Testing the Addition of the Immune Therapy Drugs, Tocilizumab and Atezolizumab, to Radiation Therapy for Recurrent Glioblastoma
  • Official Title: A Safety Run-In and Phase II Study Evaluating the Efficacy, Safety, and Impact on the Tumor Microenvironment of the Combination of Tocilizumab, Atezolizumab, and Fractionated Stereotactic Radiotherapy in Recurrent Glioblastoma

Clinical Trial IDs

  • ORG STUDY ID: NCI-2021-00410
  • SECONDARY ID: NCI-2021-00410
  • SECONDARY ID: NRG-BN010
  • SECONDARY ID: NRG-BN010
  • SECONDARY ID: U10CA180868
  • NCT ID: NCT04729959

Conditions

  • Diffuse Astrocytoma, IDH-Wildtype
  • Recurrent Glioblastoma

Interventions

DrugSynonymsArms
AtezolizumabMPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG7446, RO5541267, TecentriqGroup I (tocilizumab, atezolizumab, FSRT)
TocilizumabActemra, Immunoglobulin G1, Anti-(Human Interleukin 6 Receptor) (Human-Mouse Monoclonal MRA Heavy Chain), Disulfide with Human-Mouse Monoclonal MRA Kappa-Chain, Dimer, MRA, R-1569, RoActemraGroup I (tocilizumab, atezolizumab, FSRT)

Purpose

This phase II trial studies the best dose and effect of tocilizumab in combination with atezolizumab and stereotactic radiation therapy in treating glioblastoma patients whose tumor has come back after initial treatment (recurrent). Tocilizumab is a monoclonal antibody that binds to receptors for a protein called interleukin-6 (IL-6), which is made by white blood cells and other cells in the body as well as certain types of cancer. This may help lower the body's immune response and reduce inflammation. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Fractionated stereotactic radiation therapy uses special equipment to precisely deliver multiple, smaller doses of radiation spread over several treatment sessions to the tumor. The goal of this study is to change a tumor that is unresponsive to cancer therapy into a more responsive one. Therapy with fractionated stereotactic radiotherapy in combination with tocilizumab may suppress the inhibitory effect of immune cells surrounding the tumor and consequently allow an immunotherapy treatment by atezolizumab to activate the immune response against the tumor. Combination therapy with tocilizumab, atezolizumab and fractionated stereotactic radiation therapy may shrink or stabilize the cancer better than radiation therapy alone in patients with recurrent glioblastoma.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the maximum-tolerated dose (MTD) among three sequential dose levels:
      single-agent tocilizumab 4 mg/kg, single-agent tocilizumab 8 mg/kg, and tocilizumab 8 mg/kg +
      atezolizumab 1680 mg (each administered with fractionated stereotactic radiation therapy
      [FSRT]), to be used for subsequent phase II testing. (Safety Run-In) II. To determine the
      efficacy of the combination of tocilizumab (anti-IL6R), atezolizumab (anti-PD-L1), and FSRT
      in recurrent glioblastoma (GBM), as measured by the objective radiographic response rate
      (ORR). (Phase II [Non-Surgical Cohort])

      SECONDARY OBJECTIVES:

      I. To estimate the progression-free survival (PFS) in patients with recurrent GBM treated
      with the combination of tocilizumab (anti-IL6R), and FSRT (and atezolizumab [anti-PD-L1], if
      dose level 3 is MTD). (Phase II Non-Surgical Cohort and Safety Run-in).

      II. To estimate the overall survival (OS) in patients with recurrent GBM treated with the
      combination of tocilizumab (anti-IL6R) and FSRT (and atezolizumab [anti-PD-L1], if dose level
      3 is MTD)), atezolizumab (anti-PD-L1), and FSRT. (Phase II Non-Surgical Cohort and Safety
      Run-in) III. To estimate the progression-free survival (PFS) in patients with recurrent GBM
      treated with the combination of tocilizumab (anti-IL6R), atezolizumab (anti-PD-L1), and FSRT.
      (Phase II Surgical Cohort) IV. To estimate the overall survival (OS) in patients with
      recurrent GBM treated with the combination of tocilizumab (anti-IL6R), atezolizumab
      (anti-PD-L1), and FSRT. (Phase II Surgical Cohort) V. To determine the rate and severity of
      adverse events (AEs) of the combination of tocilizumab (anti-IL6R), atezolizumab
      (anti-PD-L1), and FSRT in recurrent glioblastoma according to Common Terminology Criteria for
      Adverse Events (CTCAE) version (v) 5.0. (Separately in the Nonsurgical and Surgical Cohorts)

      EXPLORATORY OBJECTIVES:

      I. To determine the effect of the combination of atezolizumab (anti-PD-L1) and FSRT, with
      versus (vs.) without tocilizumab (anti-IL6R), on the GBM immune microenvironment (phase II
      surgical cohort).

      II. To evaluate the pharmacodynamic impact of the combination of tocilizumab (anti-IL6R),
      atezolizumab (anti-PD-L1), and FSRT on peripheral blood immune cell populations (phase II
      surgical cohort).

      III. To detect tumor and/or blood biomarkers associated with the outcomes of OS, PFS, and/or
      ORR in patients with recurrent GBM treated with the combination of tocilizumab (anti-IL6R),
      atezolizumab (anti-PD-L1), and FSRT (phase II non-surgical cohort).

      OUTLINE:

      SAFETY RUN-IN: Patients receive systemic treatment with either tocilizumab intravenously (IV)
      over 60 minutes with or without atezolizumab IV over 30-60 minutes on day 1. Within 3-7 days,
      patients undergo FSRT for 3 fractions over 3-5 days. Starting 4 weeks from the first dose of
      systemic treatment, patients resume treatment with tocilizumab with or without atezolizumab.
      Treatment repeats every 4 weeks for up to 2 years in the absence of disease progression or
      unacceptable toxicity.

      GROUP I (NON-SURGICAL COHORT): Patients receive systemic treatment with tocilizumab IV over
      60 minutes with or without atezolizumab IV over 30-60 minutes (dependent upon the results of
      the Safety Run-In) on day 1. Within 3-7 days, patients undergo FSRT for 3 fractions over 3-5
      days in the absence of disease progression or unacceptable toxicity. Starting 4 weeks from
      the first dose of systemic treatment, patients resume treatment with tocilizumab with or
      without atezolizumab. Treatment repeats every 4 weeks for up to 2 years in the absence of
      disease progression or unacceptable toxicity.

      GROUP II (SURGICAL COHORT): Patients are randomized to 1 of 2 arms.

      ARM I: Patients receive systemic treatment with tocilizumab IV over 60 minutes with or
      without atezolizumab IV over 30-60 minutes (dependent upon the results of the Safety Run-In)
      on day 1. Within 3-7 days, patients undergo FSRT for 3 fractions over 3-5 days. Within 7-14
      days after FSRT, patients undergo surgery. Within 21-24 days from the first dose of systemic
      treatment, patients resume treatment with tocilizumab with or without atezolizumab. Treatment
      repeats every 4 weeks for up to 2 years in the absence of disease progression or unacceptable
      toxicity.

      ARM II: Patients receive systemic treatment with atezolizumab IV over 30-60 minutes on day 1.
      Within 3-7 days, patients undergo FSRT for 3-5 fractions over 3-5 days. Within 7-14 days
      after FSRT, patients undergo surgery. Within 21-24 days from the first dose of systemic
      treatment, patients resume treatment with tocilizumab IV over 60 minutes with or without
      atezolizumab. Treatment repeats every 4 weeks for up to 2 years in the absence of disease
      progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 30 days, 3, 6, 9, 12, 18,
      and 24 months.
    

Trial Arms

NameTypeDescriptionInterventions
Group I (tocilizumab, atezolizumab, FSRT)ExperimentalPatients receive systemic treatment with tocilizumab IV over 60 minutes with or without atezolizumab IV over 30-60 minutes (dependent upon the results of the Safety Run-In) on day 1. Within 3-7 days, patients undergo FSRT for 3 fractions over 3-5 days in the absence of disease progression or unacceptable toxicity. Starting 4 weeks from the first dose of systemic treatment, patients resume treatment with tocilizumab with or without atezolizumab. Treatment repeats every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.
  • Atezolizumab
  • Tocilizumab
Group II, Arm I (tocilizumab, atezolizumab, FSRT, surgery)ExperimentalPatients receive systemic treatment with tocilizumab IV over 60 minutes with or without atezolizumab IV over 30-60 minutes (dependent upon the results of the Safety Run-In) on day 1. Within 3-7 days, patients undergo FSRT for 3 fractions over 3-5 days. Within 7-14 days after FSRT, patients undergo surgery. Within 21-24 days from the first dose of systemic treatment, patients resume treatment with tocilizumab with or without atezolizumab. Treatment repeats every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.
  • Atezolizumab
  • Tocilizumab
Group II, Arm II (tocilizumab, atezolizumab, FSRT, surgery)ExperimentalPatients receive systemic treatment with atezolizumab IV over 30-60 minutes on day 1. Within 3-7 days, patients undergo FSRT for 3-5 fractions over 3-5 days. Within 7-14 days after FSRT, patients undergo surgery. Within 21-24 days from the first dose of systemic treatment, patients resume treatment with tocilizumab IV over 60 minutes with or without atezolizumab. Treatment repeats every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.
  • Atezolizumab
  • Tocilizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Histopathologically proven diagnosis of glioblastoma, OR molecular diagnosis of
             glioblastoma per Consortium to Inform Molecular and Practical Approaches to Central
             Nervous System Tumor Taxonomy (c-IMPACT-NOW) criteria ("diffuse astrocytic glioma,
             IDH-wildtype, with molecular features of glioblastoma, World Health Organization [WHO]
             grade IV"; this requires presence of amplification of EGFR, whole chromosome 7 gain
             AND whole chromosome 10 loss, or TERT promoter mutation)

          -  Tumor that is in first recurrence following prior first-line radiation therapy (prior
             dose >= 40 Gy). Prior temozolomide, prior tumor-treating fields, and/or Gliadel wafers
             (if placed at initial tumor resection) are allowed, but none of these are required

          -  Unequivocal radiographic evidence of tumor progression by contrast-enhanced magnetic
             resonance imaging (MRI) scan within 21 days prior to registration

          -  Per radiation oncologist review of MRI within 21 days prior to registration, must have
             focus of progressive, contrast-enhancing tumor that is amenable to FSRT, defined as
             the following:

               -  At least 1 cm x 1 cm contrast-enhancing tumor that is no greater than 4 cm in
                  largest dimension

               -  FSRT target is at least 0.5 cm from the optic chiasm and brainstem

               -  Of note, multifocal disease (i.e., other sites of tumor beyond the tumor being
                  targeted for FSRT) is allowed if the above criteria are met for the tumor that is
                  the proposed target for FSRT

          -  Surgical cohort only (Phase II only):

               -  Must be a candidate for repeat surgery (significant debulking or gross total
                  resection of the contrast enhancing area) as determined by the neurosurgeon or
                  multidisciplinary team

          -  Tumor O-6-methylguanine-deoxyribonucleic acid (DNA) methyltransferase (MGMT)
             methylation status must be available from any prior GBM tumor specimen; results of
             routinely used methods for MGMT methylation testing (e.g. mutagenically separated
             polymerase chain reaction [MSPCR] or quantitative polymerase chain reaction [PCR]) are
             acceptable)

          -  The following intervals from previous treatments to registration are required to be
             eligible:

               -  If prior radiation was < 60 Gy, an interval of at least 12 weeks (84 days) must
                  have elapsed since the completion of radiation therapy

               -  If prior radiation was >= 60 Gy, an interval of least 6 months (182 days) must
                  have elapsed since the completion of radiation therapy, unless the target lesion
                  for FSRT is outside of the 80% isodose line of the original radiation plan

               -  At least 21 days from temozolomide

               -  At least 28 days from any investigational (not Food and Drug Administration
                  [FDA]-approved for glioblastoma) agents, or within a time interval less than at
                  least 5 half-lives of the investigational agent whichever is shorter (Note:
                  anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapeutic antibody or pathway-targeting
                  agents are not allowed)

          -  Age >= 18 years

          -  Karnofsky performance status >= 70 within 14 days prior to registration

          -  History/physical examination within 14 days prior to registration

          -  Leukocytes >= 2,500/mm^3 (within 14 days prior to registration)

          -  Absolute neutrophil count >= 1,500/mm^3 (within 14 days prior to registration)

          -  Absolute lymphocyte count >= 800/mm^3 (within 14 days prior to registration)

          -  Platelets >= 100,000/mm^3 (within 14 days prior to registration)

          -  Hemoglobin >= 8 g/dL (within 14 days prior to registration)

          -  Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (however, patients
             with known Gilbert disease who have serum bilirubin level =< 3 x ULN may be enrolled)
             (within 14 days prior to registration)

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =<
             2.5 x ULN (within 14 days prior to registration)

          -  Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 x
             ULN (within 14 days prior to registration)

          -  Alkaline phosphatase =< 2.5 x ULN (within 14 days prior to registration)

          -  Creatinine clearance >= 30 mL/min/1.73 m^2 by Cockcroft-Gault (within 14 days prior to
             registration)

          -  Women of child-bearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control; abstinence) prior to study entry, for
             the duration of receipt of study treatment, and for 60 days (males) or 90 days
             (females) from the last dose of tocilizumab and for 5 months (150 days) after the last
             dose of atezolizumab. Administration of atezolizumab or tocilizumab may have an
             adverse effect on pregnancy and poses a risk to the human fetus, including
             embryo-lethality. Should a woman become pregnant or suspect she is pregnant while she
             or her partner is participating in this study, she should inform her treating
             physician immediately

          -  Women of childbearing potential must have a negative serum or urine pregnancy test
             within 14 days prior to registration

          -  Patients positive for human immunodeficiency virus (HIV) are allowed on study (note:
             HIV testing is not required), but HIV-positive patients must have:

               -  An undetectable viral load within 6 months of registration

               -  A stable regimen of highly active anti-retroviral therapy (HAART)

               -  No requirement for concurrent antibiotics or antifungal agents for the prevention
                  of opportunistic infections

          -  For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral
             load must be undetectable on suppressive therapy, if indicated.

               -  Note: Known positive test for hepatitis B virus surface antigen (HBV sAg)
                  indicating acute or chronic infection would make the patient ineligible unless
                  the viral load becomes undetectable on suppressive therapy. Patients who are
                  immune to hepatitis B (anti-Hepatitis B surface antibody positive) are eligible
                  (e.g. patients immunized against hepatitis B

          -  For patients with a history of hepatitis C virus (HCV) infection must have been
             treated and cured. For patients with HCV infection who are currently on treatment,
             they are eligible if they have an undetectable HCV viral load.

               -  Note: Known positive test for hepatitis C virus ribonucleic acid (HCV ribonucleic
                  acid [RNA]) indicating acute or chronic infection would make the patient
                  ineligible unless the viral load becomes undetectable on suppressive therapy

          -  The patient or a legally authorized representative must provide study-specific
             informed consent prior to study entry

          -  Availability of prior radiotherapy treatment plan details in Digital Imaging and
             Communications in Medicine (DICOM) format

        Exclusion Criteria:

          -  Known somatic tumor mutation in IDH1 or IDH2 gene. If not previously completed,
             sequencing of the IDH1 and IDH2 genes is not required to determine trial eligibility

          -  Known germline DNA repair defect (mismatch repair deficiency, POLE mutation, e.g.). If
             not previously completed, germline sequencing is not required to determine trial
             eligibility

          -  Diffuse leptomeningeal disease

          -  Known contrast-enhancing tumor in brainstem or spinal cord. If not previously
             completed, spinal imaging is not required to determine trial eligibility

          -  Patients with clinically significant mass effect or midline shift (e.g., 1-2 cm of
             midline shift)

          -  Prior bevacizumab therapy

          -  Patients with a prior or concurrent malignancy whose natural history or treatment has
             the potential to interfere with the safety or efficacy assessment of the
             investigational regimen are excluded from this trial. Otherwise, patients with prior
             or concurrent malignancy are eligible

          -  Patients with prior allogeneic bone marrow transplantation or prior solid organ
             transplantation

          -  Prior treatment with anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapeutic antibody or
             pathway-targeting agents

          -  Treatment with systemic immunostimulatory agents (including, but not limited to,
             interferon [IFN]-alpha or interleukin [IL]-2) within 4 weeks prior to registration

          -  Treatment with systemic immunosuppressive medications (including, but not limited to,
             cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis
             factor [anti-TNF] agents) within 2 weeks prior to registration

          -  Systemic corticosteroids used to treat brain edema and/or related symptoms at a dose
             of > 2 mg of dexamethasone (or equivalent) daily within 5 days prior to registration.
             Patients receiving systemic corticosteroids for other indications are excluded

          -  Patients with increased risk for gastrointestinal perforations including history of
             diverticulitis

          -  Known hypersensitivity to Chinese hamster ovary cell products or other recombinant
             human antibodies

          -  History of severe allergic, anaphylactic, or other hypersensitivity reactions to
             chimeric or humanized antibodies or fusion proteins

          -  Known clinically significant liver disease, including active viral, alcoholic, or
             other hepatitis; cirrhosis; fatty liver; and inherited liver disease

          -  History or risk of autoimmune disease, including, but not limited to, systemic lupus
             erythematosus, rheumatoid arthritis, psoriatic arthritis, inflammatory bowel disease,
             vascular thrombosis associated with antiphospholipid syndrome, Wegener's
             granulomatosis, Sjogren's syndrome, Bell's palsy, Guillain-Barre syndrome, multiple
             sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis.

               -  Note: patients with the below conditions are eligible:

                    -  Autoimmune hypothyroidism on a stable dose of thyroid replacement hormone
                       are eligible.

                    -  Controlled type 1 diabetes mellitus on a stable insulin regimen are
                       eligible.

                    -  Eczema, psoriasis, lichen simplex chronicus or vitiligo with dermatologic
                       manifestations only permitted provided that they meet the following
                       conditions:

                         -  Patients with psoriasis must have a baseline ophthalmologic exam to
                            rule out ocular manifestations

                         -  Rash must cover less than 10% of body surface area (BSA)

                         -  Disease is well controlled at baseline and only requiring low potency
                            topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate
                            0.1%, fluocinolone 0.01%, desonide 0.05%, alclometasone dipropionate
                            0.05%)

                    -  No acute exacerbations of underlying condition within the last 12 months
                       (not requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate,
                       retinoids, biologic agents, oral calcineurin inhibitors; high potency or
                       oral steroids)

          -  History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), or
             organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing
             pneumonia, etc.). History of radiation pneumonitis in a prior radiation field
             (fibrosis) is permitted

          -  Patients with active tuberculosis (TB) are excluded

          -  Severe infections within 3 weeks prior to registration including, but not limited to,
             hospitalization for complications of infection, bacteremia, or severe pneumonia

          -  Signs or symptoms of infection within 1 week prior to registration

          -  Received oral or intravenous (IV) antibiotics within 2 weeks prior to registration.
             Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract
             infection or chronic obstructive pulmonary disease) are eligible

          -  Major surgical procedure within 21 days prior to registration or anticipation of need
             for a major surgical procedure during the course of study treatment

          -  Administration of a live, attenuated vaccine within 4 weeks before registration or
             anticipation that such a live, attenuated vaccine will be required during receipt of
             study treatment and up to 5 months after the last dose of study drug

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements

          -  Women who are pregnant or nursing (and unwilling to discontinue) are excluded from
             this study. Atezolizumab and tocilizumab are agents with the potential for teratogenic
             or abortifacient effects. Because there is an unknown but potential risk for adverse
             events in nursing infants secondary to treatment of the mother with atezolizumab and
             tocilizumab breastfeeding should be discontinued if the mother is treated with
             atezolizumab and tocilizumab
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose-limiting toxicities (Safety Run-In)
Time Frame:Up to 1 post-fractionated stereotactic radiation therapy (FRST) cycle of systemic therapy for which dose-limiting toxicity is reached (1 cycle = 4 weeks)
Safety Issue:
Description:Will be assessed by Common Terminology Criteria for Adverse Events version 5.0.

Secondary Outcome Measures

Measure:Progression-free survival (PFS) (Phase II, Non-Surgical Cohort)
Time Frame:Time from study enrollment to disease progression or death from any cause, assessed up to 2 years
Safety Issue:
Description:PFS curves will be assessed via the Kaplan-Meier method.
Measure:Overall survival (Phase II, Non-Surgical Cohort)
Time Frame:From study enrollment to death from any cause, assessed up to 2 years
Safety Issue:
Description:Will be assessed via the Kaplan-Meier method.
Measure:Progression-free survival (Phase II, Non-Surgical Cohort)
Time Frame:From randomization to disease progression or death from any cause, assessed up to 2 years
Safety Issue:
Description:Kaplan-Meier method will be used to estimate the PFS within each randomized arm separately as well as combined.
Measure:Overall survival (Phase II, Surgical Cohort)
Time Frame:From study enrollment to death from any cause, assessed up to 2 years
Safety Issue:
Description:Will be assessed via the Kaplan-Meier method.
Measure:Incidence of adverse events (Surgical Cohort and Non-Surgical Cohort)
Time Frame:Up to 2 years
Safety Issue:
Description:Will be graded according to Common Terminology Criteria for Adverse Events version 5.0. Comprehensive summaries of all adverse events by treatment arm will be generated and examined. Counts and frequencies of worst (highest score) adverse event per patient will be presented overall and by adverse event type category, separately by assigned treatment group. The proportion of patients with at least one grade 3 or higher adverse event will be compared between treatment arm. Similarly, frequencies for specific potentially treatment related adverse events where grade 3 or higher events are noted may be compared. Any frequencies to be tested will be evaluated using the chi-square or exact test as appropriate, with two-sided significance level 0.05.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:National Cancer Institute (NCI)

Last Updated

August 25, 2021