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

  • STATUS
    Recruiting
  • End date
    Dec 25, 2023
  • participants needed
    50
  • sponsor
    Dana-Farber Cancer Institute
Updated on 25 March 2022
ct scan
platelet count
corticosteroids
biologic agent
karnofsky performance status
neutrophil count
ipilimumab
tumor progression
alopecia
mirena
lymphopenia
ebrt
definitive radiation therapy
recurrent meningioma
multiple endocrine neoplasia

Summary

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.

Description

This research is a Phase II clinical trial, which means it will test the safety and effectiveness of nivolumab alone (Cohort 1) or in combination with ipilimumab (Cohort 2). Both nivolumab and ipilimumab are antibodies (types of human protein) that work 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 and ipilimumab have both been used in other research studies and information from those other research studies suggests that these interventions 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. The FDA has not approved the combination of nivolumab and ipilimumab for your specific disease, but it has been approved for other uses.

Details
Condition Meningiomas
Treatment Nivolumab, Nivolumab - 240 mg, Ipilimumab - 3 mg/kg, Nivolumab - 480 mg, Nivolumab - 1 mg/kg, External Beam RT, Ipilimumab - 1 mg/kg, Nivolumab - 3 mg/kg
Clinical Study IdentifierNCT02648997
SponsorDana-Farber Cancer Institute
Last Modified on25 March 2022

Eligibility

Yes No Not Sure

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
Be 18 years of age on day of signing informed consent
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)
Participants must demonstrate adequate organ and marrow function as defined below (all screening labs to be performed within 14 days of treatment initiation)
Have a Karnofsky performance status (KPS) ≥ 70 (Appendix A)
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)
(GFR can be used in place of creatinine or creatinine clearance)
Serum creatinine ≤ 1.5 X ULN OR
creatinine clearance (meas or calc) ≥ 60 mL/min for participants with creatinine levels > 1.5 X ULN
(except participants with Gilbert's Syndrome, who can have a total bili < 5 X ULN)
Total serum bilirubin ≤ 1.5 X ULN
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
Resting baseline oxygen saturation ≥ 92% at rest by pulse oximetry
For cohort 2, patients must be a candidate for external beam radiotherapy including either conventional fractionated conformal dosing or stereotactic radiosurgical boost dosing (participants may enroll if they are receiving radiotherapy or have completed it within 8 weeks of starting immunotherapy)
MRI (or CT if MRI contraindicated) within 14 days prior to start of study drug
For cohort 2 patients who are undergoing fractionated conformal re-irradiation to a tumor site that has been previously irradiated, an interval of at least 6 months must have passed since they completed their prior irradiation to be eligible unless the current course of radiation is targeting a new area of tumor growth outside the 80% isodose line of the original radiation field as determined by the treating investigator
Corticosteroid dose must be stable or decreasing for at least 5 days prior to
The effects of nivolumab on the developing human fetus are unknown. For this reason
the scan. If steroids are added or the steroid dose is increased between the
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 24 hours of starting study therapy
date of the screening MRI or CT scan and the start of treatment, a new
Women must not be breastfeeding
baseline MRI or CT is required
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 months after the last dose of Nivolumab
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 7 months after the last dose of Nivolumab
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
Progestogen only hormonal contraception associated with inhibition of ovulation
Intrauterine hormone-releasing system (IUS)
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
UNACCEPTABLE METHODS OF CONTRACEPTION
Periodic abstinence (calendar, symptothermal, post-ovulation methods)
Withdrawal (coitus interruptus)
Spermicide only
Lactation amenorrhea method (LAM)
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
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
All patients: Previous treatment with PD-1 or PD-L1 directed therapy
Cohort 2 patients: Previous treatment with CTLA-4 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
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
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
No concurrent treatment on another clinical trial. Supportive care trials or nontreatment 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
Has received a live vaccine within 30 days prior to the first dose of study drug
Medical History
seasonal influenza vaccination is permitted excluding the nasal spray
History of intracranial abscess within 6 months prior to start of study therapy
formulation
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
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