Clinical Trials /

An Open-Label Phase II Study of Nivolumab in Adult Participants With Recurrent High-Grade Meningioma

NCT02648997

Description:

This research study is studying targeted immunotherapies as a possible treatment for recurrent meningioma. The names of the study interventions involved in this study are nivolumab and ipilimumab.

Related Conditions:
  • Meningioma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Nivolumab in Adult Participants With Recurrent High-Grade Meningioma
  • Official Title: A Single Arm, Open-Label Phase II Study of Nivolumab in Adult Participants With Recurrent High-Grade Meningioma

Clinical Trial IDs

  • ORG STUDY ID: 15-490
  • NCT ID: NCT02648997

Conditions

  • Meningiomas

Interventions

DrugSynonymsArms
NivolumabOpdivo, BMS-936558, ONO-4538Nivolumab Immunotherapy

Purpose

This research study is studying a targeted immunotherapy as a possible treatment for Recurrent Meningioma. The name of the study intervention involved in this study is Nivolumab.

Detailed Description

      This research is a Phase II clinical trial, which mean it will test the safety and
      effectiveness of Nivolumab. Nivolumab is an antibody (type of human protein) that works to
      stop tumor cells from growing and multiplying by immunotherapy. Immunotherapy is trying to
      have the body's own immune system work against tumor cells.

      Nivolumab has been used in other research studies and information from those other research
      studies suggests that this intervention may help to stop Meningioma cells from growing.
      Nivolumab is FDA approved to treat other types of cancers, but the FDA (the U.S. Food and
      Drug Administration) has not yet approved this intervention for this type of cancer.
    

Trial Arms

NameTypeDescriptionInterventions
Nivolumab ImmunotherapyExperimentalNivolumab will be administered very 2 weeks at a pre-determined dose.
  • Nivolumab

Eligibility Criteria

        Inclusion Criteria:

          -  Have histologically confirmed WHO grade II or III meningioma that is progressive or
             recurrent. Metastatic meningiomas are allowed. Participants must have failed maximal
             safe resection and radiation therapy.

          -  Prior therapy:

          -  There is no limit on the number of prior surgeries, radiation therapy, radiosurgery
             treatments or systemically administered therapeutic agents.

               -  Patients may have been treated with standard external beam radiation or
                  radiosurgery in any combination, however, an interval of ≥ 12 weeks (84 days)
                  must have elapsed from the completion of the radiation therapy to start of study
                  therapy 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).

               -  In addition, there must be subsequent evidence of tumor progression after
                  completion of radiation therapy;

               -  An interval of ≥ 28 days and full recovery (no ongoing safety issues) from
                  surgical resection

               -  An interval of ≥ 7 days from stereotactic biopsy;

          -  For prior systemic agents, participants must be at least 4 weeks (or 5 half-lives,
             whichever is shorter) from other prior cytotoxic chemotherapy (6 weeks from
             nitrosoureas) or biologic therapies.

          -  Participants must have recovered to grade ≤ 1 or pretreatment baseline from
             clinically significant adverse events related to prior therapy (exclusions include
             but are not limited to alopecia, laboratory values listed per inclusion criteria and
             lymphopenia);

          -  Be 18 years of age on day of signing informed consent.

          -  Have a Karnofsky performance status (KPS) ≥ 70 (Appendix A).

          -  Participants must demonstrate adequate organ and marrow function as defined below
             (all screening labs to be performed within 14 days of treatment initiation):

               -  White blood cell (WBC) ≥ 2000/mm3

               -  Absolute neutrophil count (ANC) ≥ 1,000/mm3

               -  Platelet count ≥ 100,000/mm3

               -  Hemoglobin ≥ 9 gm/dl

               -  AST(SGOT)/ALT(SGPT) ≤ 3 x laboratory upper limit of normal (ULN)

               -  Serum creatinine ≤ 1.5 X ULN OR

               -  creatinine clearance (meas or calc) ≥ 60 mL/min for participants with creatinine
                  levels > 1.5 X ULN

               -  (GFR can be used in place of creatinine or creatinine clearance)

               -  Total serum bilirubin ≤ 1.5 X ULN

               -  (except participants with Gilbert's Syndrome, who can have a total bili < 5 X
                  ULN)

               -  Resting baseline oxygen saturation ≥ 92% at rest by pulse oximetry

          -  MRI (or CT if MRI contraindicated) within 14 days prior to start of study drug.
             Corticosteroid dose must be stable or decreasing for at least 5 days prior to the
             scan. If steroids are added or the steroid dose is increased between the date of the
             screening MRI or CT scan and the start of treatment, a new baseline MRI or CT is
             required.

          -  Ability to understand and the willingness to comply with scheduled visits, treatment
             schedule, laboratory testing, and other requirements of the study, including disease
             assessment by MRI (or CT), as confirmed by signing a written informed consent
             document.

          -  The effects of nivolumab on the developing human fetus are unknown. For this reason:

          -  Women of childbearing potential (WOCPB; defined in Section 3.4) must have a negative
             serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of
             HCG) within 72 hours of starting study therapy;

          -  Women must not be breastfeeding;

          -  WOCPB must agree to follow instructions for method(s) of contraception from the time
             of enrollment for the duration of treatment with study therapy plus 5 half-lives of
             study drug plus 30 days (during ovulatory cycle) for a total of 23 weeks
             post-treatment completion.

          -  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.

          -  Men who are sexually active with WOCBP must agree to follow instructions for
             method(s) of contraception for the duration of treatment with study drug plus 5
             half-lives of study drug plus 90 days (duration of sperm turnover) for a total of 31
             weeks post-treatment completion.

          -  Investigators shall counsel WOCBP and male subjects who are sexually active with
             WOCBP on the importance of pregnancy prevention and the implications of an unexpected
             pregnancy Investigators shall advise WOCBP and male subjects who are sexually active
             with WOCBP on the use of highly effective methods of contraception. Highly effective
             methods of contraception have a failure rate of < 1% per year when used consistently
             and correctly.

          -  At a minimum, subjects must agree to the use of two methods of contraception, with
             one method being highly effective and the other method being either highly effective
             or less effective as listed below:

               -  HIGHLY EFFECTIVE METHODS OF CONTRACEPTION

                    -  Male condoms with spermicide

                    -  Hormonal methods of contraception including combined oral contraceptive
                       pills, vaginal ring, injectables, implants, and intrauterine devices (IUDs)
                       such as Mirena by WOCBP subjects or male subject's WOCBP partner. Female
                       partners of male subjects participating in the study may use hormone based
                       contraceptives as one of the acceptable methods of contraception since they
                       will not be receiving study drug

                    -  Nonhormonal IUDs, such as ParaGard

                    -  Tubal ligation

                    -  Vasectomy

                    -  Complete Abstinence - Complete abstinence is defined as complete avoidance
                       of heterosexual intercourse and is an acceptable form of contraception for
                       all study drugs. Subjects who choose complete abstinence are not required
                       to use a second method of contraception, but female subjects must continue
                       to have pregnancy tests. Acceptable alternate methods of highly effective
                       contraception must be discussed in the event that the subject chooses to
                       forego complete abstinence.

               -  LESS EFFECTIVE METHODS OF CONTRACEPTION

                    -  Diaphragm with spermicide

                    -  Cervical cap with spermicide

                    -  Vaginal sponge

                    -  Male Condom without spermicide

                    -  Progestin only pills by WOCBP subjects or male subject's WOCBP partner

                    -  Female Condom - A male and female condom must not be used together

          -  NOTE: Azoospermic males and WOCBP who are continuously not heterosexually active are
             exempt from contraceptive requirements. However, WOCBP participants must still
             undergo pregnancy testing as described.

        Exclusion Criteria:

          -  Current or planned participation in a study of an investigational agent or using an
             investigational device.

          -  Tumors that are primarily localized to the brainstem or spinal cord;

          -  Evidence of intratumoral or peritumoral hemorrhage on baseline MRI scan other than
             those that are grade ≤ 1 and either post-operative or stable on at least 2
             consecutive MRI scans;

          -  Prior Therapy:

          -  Prior treatment with systemic immunosuppressive treatments, aside from systemic
             dexamethasone therapy for cerebral edema, such as methotrexate, chloroquine,
             azathioprine, etc. within 3 months of start of study therapy;

          -  Prior treatment with interstitial brachytherapy within 6 months of start of study
             therapy;

          -  Previous treatment with PD-1 or PD-L1 directed therapy;

          -  Surgical procedure (including open biopsy, surgical resection, wound revision, or any
             other major surgery involving entry into a body cavity) or significant traumatic
             injury within 28 days prior to first study treatment, or anticipation of need for
             major surgical procedure during the course of the study;

          -  Minor surgical procedure (eg, stereotactic biopsy within 7 days of first study
             treatment; placement of a vascular access device within 2 days of first study
             treatment);

          -  Other Meds:

          -  Participants who are receiving any other investigational agents.

          -  Immunosuppressive medications / steroids:

               -  Subject must not require high dose systemic corticosteroids defined as
                  dexamethasone > 4 mg/day or bioequivalent for at least 3 consecutive days within
                  2 weeks prior to Day 1of study therapy;

               -  Inhaled or topical steroids and adrenal replacement doses > 10 mg daily
                  prednisone equivalents are permitted in the absence of active autoimmune
                  disease.

               -  Subjects are permitted to use topical, ocular, intra-articular, intranasal, and
                  inhalational corticosteroids (with minimal systemic absorption).

               -  Physiologic replacement doses of systemic corticosteroids are permitted, even if
                  > 10 mg/day prednisone equivalents.

               -  A brief course of corticosteroids for prophylaxis (eg, contrast dye allergy) or
                  for treatment of non-autoimmune conditions (eg, delayed-type hypersensitivity
                  reaction caused by contact allergen) is permitted.

          -  Has received a live vaccine within 30 days prior to the first dose of study drug;
             seasonal influenza vaccination is permitted excluding the nasal spray formulation;

          -  No concurrent treatment on another clinical trial. Supportive care trials or non-
             treatment trials, e.g. quality of life, are allowed;

          -  Concomitant Medical Illnesses: Uncontrolled intercurrent illness, including-but not
             limited to:

          -  Known additional malignancy that is progressing or requires active treatment within 3
             years of start of study drug. 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;

          -  Has evidence of interstitial lung disease or active, non-infectious pneumonitis;

          -  Any serious or uncontrolled medical disorder that, in the opinion of the
             investigator, may increase the risk associated with study participation or study drug
             administration, impair the ability of the subject to receive protocol therapy, or
             interfere with the interpretation of study results examples include but are not
             limited to symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia or psychiatric illness/social situations that would limit compliance with
             study requirements;

          -  Has an active autoimmune disease requiring systemic treatment within the past 3
             months or a documented history of clinically severe autoimmune disease, or a syndrome
             that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo,
             type 1 diabetes mellitus, residual hypothyroidism due to autoimmune condition
             requiring hormone replacement, psoriasis not requiring systemic treatment, conditions
             not expected to recur in the absence of an external trigger or resolved childhood
             asthma/atopy would be exceptions 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;

          -  Has an active infection requiring intravenous therapy;

          -  Positive test for hepatitis B virus surface antigen (HBV sAg) or detectable hepatitis
             C virus ribonucleic acid (HCV RNA) indicating acute or chronic infection

          -  Medical History:

          -  History of intracranial abscess within 6 months prior to start of study therapy;

          -  Known history of testing positive for human immunodeficiency virus (HIV) or known
             acquired immunodeficiency syndrome (AIDS);

          -  NOTE: HIV-positive participants on combination antiretroviral therapy are ineligible
             because of the potential for pharmacokinetic interactions with Nivolumab. Appropriate
             studies will be undertaken in participants receiving combination antiretroviral
             therapy when indicated.

          -  History of allergy to study drug components

          -  History of severe hypersensitivity reaction to any monoclonal antibody;

          -  Prisoners or participants who are involuntarily incarcerated;

          -  Pregnant women are excluded from this study because Nivolumab is an agent 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 Nivolumab, breastfeeding should be discontinued if the mother is treated
             Nivolumab.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-Free Survival At Six Months Following Initiation Of Study Therapy
Time Frame:6 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Median Overall Survival
Time Frame:2 years
Safety Issue:
Description:
Measure:Objective Radiologic Response Rate
Time Frame:2 years
Safety Issue:
Description:
Measure:Number of participants with treatment related adverse events as assessed by CTCAE v4.0.
Time Frame:2 years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Dana-Farber Cancer Institute

Trial Keywords

  • Atypical Meningioma
  • Anaplastic Meningioma

Last Updated

October 1, 2016