Phase Ib /II Clinical Trial of Nivolumab Monotherapy and Nivolumab in Combination with Ipilimumab in Pediatric Subjects with High Grade Primary CNS Malignancies
- Conditions
- Brain CancerCNS Malignancies10029211
- Registration Number
- NL-OMON48940
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 6
• Prior to study participation, written informed consent from participants, or in the case of minors, written permission (informed consent) from parents or legally acceptable representatives.
• Males and Females, ages >= 6 months to < 22 years old
• Participants must have received standard of care therapy, and there must be no potentially-curative treatment available, in one of the following cohorts:
1. newly diagnosed (by MRI or histology) DIPG that has been treated with radiation therapy (RT) (Cohort 1)
2. histologically confirmed recurrent or progressive non-brainstem HGG previously treated with surgical resection and RT (with or without chemotherapy) (Cohort 2)
3. histologically confirmed medulloblastoma that has relapsed or is resistant to at least one line of prior therapy including surgery, RT, and chemotherapy (regardless of age) (Cohort 3)
4. histologically confirmed ependymoma that has relapsed or is resistant to at least one line of prior therapy including surgical resection and RT (regardless of age) (Cohort 4)
5. histologically-confirmed other high grade CNS malignancy which is recurrent or progressive after at least one line of prior therapy (Cohort 5)
• If first recurrence of the CNS tumor is documented by MRI, an interval of at least 12 weeks after the end of prior radiation therapy is required unless there is either histopathologic confirmation of recurrent tumor, or new enhancement on MRI outside of the radiotherapy treatment field (Cohorts 2-5).
• A tumor sample must be available (from resection at time of recurrence, or otherwise archive sample from previous resection) for submission to central laboratory. This is not required for DIPG (Cohort 1).
• Substantial recovery (ie, no ongoing safety issues) from surgical resection prior to first dose of study therapy.
• Adequate wash-out interval since last administration of other treatment for CNS malignancies
• Able to taper (preferably discontinue) steroids. Participants must be receiving not more than 0.05 mg/kg dexamethasone per day (or equivalent) for intracranial mass effect at study entry.
• Participants who have received high-dose chemotherapy with autologous hematopoietic cell transplantation must be at least 6 months post-hematopoietic cell transplantation and they must have a CD4 count of at least 200.
• Lansky play score (LPS) for =< 16 years of age or Karnofsky performance scale (KPS) for > 16 years of age must be >= 60.
• Women of child-bearing potential must have a negative pregnancy test within 24 hours of starting treatment, and should not be breastfeeding. Women of childbearing potential, or male subjects who are sexually active with women of child-bearing potential must agree to the contraceptive requirements of the study.
• Participants with active, known, or suspected autoimmune disease.
• Participants with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of study drug administration.
• Participants who cannot undergo magnetic resonance imaging (MRI) with contrast enhancement.
• Specific blood test results indicating impaired haematological, liver or kidney function
• Participants cannot test positive for Hepatitis B/C
• Participants must not have HIV or AIDs
• Unable to taper steroids due to ongoing mass effect
• Participants with low-grade gliomas or tumors of unknown malignant potential
• Evidence of > Grade 1 recent CNS hemorrhage on the baseline MRI scan.
• Participants with bulky tumor on imaging are ineligible; bulky tumor is defined as:
i) Tumor with any evidence of uncal herniation or severe midline shift
ii) Tumor with diameter of > 6 cm in one dimension on contrast-enhanced MRI
iii) Tumor that in the opinion of the investigator, shows significant mass effect.
• Prior treatment with any antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
• Prior allogeneic hematopoietic cell transplantation (unless MM approval in advance).
• Participants who are receiving any other anti-cancer or investigational drug therapy or non-palliative radiation therapy.
• Any serious or uncontrolled medical disorder that may increase the risk associated with study participation or study drug administration, impair the ability of the participant to receive protocol therapy, or interfere with the interpretation of study results.
• Patients cannot be incarcerated or detained for a psychiatric or physical illness
• History of allergy or hypersensitivity to study drug components or to any monoclonal antibody.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>For safety lead in: To estimate the safety and tolerability of study treatments<br /><br>(firstly nivolumab alone, and then nivolumab in combination with ipilimumab) in<br /><br>pediatric participants with primary high- grade CNS tumors.<br /><br><br /><br>For expansion: To investigate efficacy of the study treatments (as assessed by<br /><br>Overall Survival and Progressive Free survival), individually in each of<br /><br>pediatric cohorts, as follows:<br /><br>Cohort 1: OS in newly diagnosed DIPG<br /><br>Cohort 2: PFS in recurrent or progressive HGG<br /><br>Cohort 3: PFS in Progressive medulloblastoma<br /><br>Cohort 4: PFS in Recurrent or progressive ependymoma<br /><br>Cohort 5: PFS in Recurrent or progressive other rare CNS tumors (including<br /><br>pineoblastoma, AT/RT, embryonic CNS tumors)</p><br>
- Secondary Outcome Measures
Name Time Method <p>To describe any observed anti-tumor activity of study treatment in pediatric<br /><br>primary high grade CNS tumors.<br /><br>To estimate the safety of study therapy in all cohorts by incidence of<br /><br>laboratory abnormalities, AEs, SAEs, drug-related AEs, AEs leading to<br /><br>discontinuation, and death.<br /><br>To further characterise the efficacy of the study treatment in each cohort by<br /><br>rates of progression free survival at 6 months and overall survival at 12<br /><br>months.</p><br>