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Study of Avelumab in combination with Lenvatinib for children with primary CNS tumors
EU CTIS ID: 2024-512940-51-00
What this study is testing
Dose Escalation Part 1 To evaluate the safety and tolerability of avelumab + lenvatinib Dose Escalation Part 1 To determine the recommended avelumab and lenvatinib dose for expansion Dose Expansion Part 2 To assess efficacy by PFS
- Human Pharmacology (Phase I)- Other
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Are ≥ 2 and < 18 years of age at the time of signing the informed consent.
- A negative serum pregnancy test at Screening for all postmenarchal girls, girls ≥ 10 years of age, or per local or institutional guidelines must be obtained.
- For participants of childbearing potential: agreement to remain abstinent or use 2 adequate methods of contraception for the duration of study intervention period and at least for 60 days after stopping the study interventions.
- A fractional shortening ≥ 30% or left ventricular ejection fraction ≥ 50% by echocardiogram or multigated acquisition (MUGA) scan within 28 days of study intervention initiation must be demonstrated.
- Participants with seizures that are well controlled are eligible and may be on antiepileptic medications, provided the dose of the antiepileptic drug(s) is/are stable.
- Participant must demonstrate an ability to comply with study protocol.
You likely can't join if
- Participants with low-grade gliomas, for example but not limited to, subependymal giant cell astrocytoma, pilocytic astrocytoma and WHO Grade 1 tumors.
- Participants are not eligible if they experience uncontrolled seizures
- Tumor surgeries a. Participants eligible for tumor surgery. b. Participants who have received major surgery (including but not limited to neurosurgical resection, brain biopsy, or radiation to the primary brain tumor) within 28 days prior to the first dose of study interventions.
- A history of intracranial hemorrhage/spinal cord hemorrhage within 28 days prior to the first dose of study interventions.
- Participants require therapeutic anticoagulation.
- Participants with a history of bleeding diathesis or recent major bleeding events considered by the Investigator as high risk for investigational drug treatment.
See the full eligibility criteria
Who can join
- Are ≥ 2 and < 18 years of age at the time of signing the informed consent.
- A negative serum pregnancy test at Screening for all postmenarchal girls, girls ≥ 10 years of age, or per local or institutional guidelines must be obtained.
- For participants of childbearing potential: agreement to remain abstinent or use 2 adequate methods of contraception for the duration of study intervention period and at least for 60 days after stopping the study interventions.
- A fractional shortening ≥ 30% or left ventricular ejection fraction ≥ 50% by echocardiogram or multigated acquisition (MUGA) scan within 28 days of study intervention initiation must be demonstrated.
- Participants with seizures that are well controlled are eligible and may be on antiepileptic medications, provided the dose of the antiepileptic drug(s) is/are stable.
- Participant must demonstrate an ability to comply with study protocol.
- Are male and/or female. a. Female participants Are not pregnant or breastfeeding, and at least one of the following conditions applies: Not a woman of childbearing potential OR If a woman of childbearing potential, use a highly effective contraceptive method (i.e., with a failure rate of < 1% per year), preferably with low user dependency, for the following time periods: Before the first dose of the study intervention(s), if using hormonal contraception: Has completed at least one 4-week cycle of an oral contraception pill and either had or has begun her menses OR Has used a depot contraceptive or extended-cycle oral contraceptive for least 28 days and has a documented negative pregnancy test using a highly sensitive assay. Highly effective contraceptive method has to be used for at least 60 days after the last dose of study intervention. Additional requirements for pregnancy testing during and after study intervention The Investigator reviews the medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a female with an early undetected pregnancy. b. Male participants -Agree to the following during the study intervention period and for at least 60 days after the last dose of study intervention: -Refrain from donating sperm PLUS, either Abstain from any activity that allows for exposure to ejaculate Refer to the Protocol for full list of criterias
- A histologically confirmed diagnosis of primary CNS malignancy as follows: a. Primary CNS tumors i The tumor should be considered high-grade histologically ii Prior radiotherapy is allowed iii For all countries except Germany: Participants must have progressed after at least 1 prior systemic therapy, except for those with diffuse midline glioma with or without the H3 K27M mutation (please refer to 2biii). For Germany only: Participants must have progressed after they have been treated based on current treatment guidelines in accordance to standardized treatment protocols, therapy optimization studies, within a disease register or via early access to upcoming standards. These treatments are administered until the end of protocol, until progressive disease, or unacceptable toxicity. Exception for participants with diffuse midline glioma with or without the H3 K27M mutation (please refer to 2biii). b. Specific for participants with diffuse midline glioma with or without the H3 K27M mutation i Prior radiotherapy is allowed ii No more than 1 prior systemic therapy is allowed iii Note: Participants with diffuse midline glioma with or without the H3 K27M mutation who have not received prior systemic therapy but have prior radiotherapy only are allowed to enroll.
- On screening scans, measurable disease by RANO criteria.
- Participants must have a Lansky performance status ≥ 50 for age ≤ 16 years or Karnofsky performance status ≥ 50 for age > 16 years at Screening.
- Adequate bone marrow function at Screening Absolute neutrophil count must be ≥ 1000/μL. Platelet count must be ≥ 100,000/mm3. Hemoglobin must be ≥ 8 g/dL.
- Adequate renal function: Screening serum creatinine must be ≤ 1.5 × upper limit of normal (ULN) or creatinine clearance > 70 mL/minute if serum creatinine > 1.5 × ULN, according to the Cockcroft-Gault formula or by 24-hour urine collection for creatinine clearance or according to local institutional standard method.
- Adequate hepatic function a. Screening total bilirubin must be ≤ 1.5 × ULN for age or direct bilirubin ≤ ULN for age if total bilirubin > 1.5 × ULN for age. b. Screening serum aspartate aminotransferase (AST) and ALT must be ≤ 3 × ULN for age.
- Screening prothrombin time/international normalized ratio (INR) must be ≤ 1.5 × institutional ULN for age.
- Availability of tissue as a formalin-fixed paraffin-embedded (FFPE) block or a minimum of 10 (preferably 25) unstained tumor slides suitable for PD-L1 expression assessment. Tumor tissue from the most recent biopsy should be submitted, and this should be from a nonirradiated area.
What rules you out
- Participants with low-grade gliomas, for example but not limited to, subependymal giant cell astrocytoma, pilocytic astrocytoma and WHO Grade 1 tumors.
- Participants are not eligible if they experience uncontrolled seizures
- Tumor surgeries a. Participants eligible for tumor surgery. b. Participants who have received major surgery (including but not limited to neurosurgical resection, brain biopsy, or radiation to the primary brain tumor) within 28 days prior to the first dose of study interventions.
- A history of intracranial hemorrhage/spinal cord hemorrhage within 28 days prior to the first dose of study interventions.
- Participants require therapeutic anticoagulation.
- Participants with a history of bleeding diathesis or recent major bleeding events considered by the Investigator as high risk for investigational drug treatment.
- Participants with urine protein ≥ 1 g protein/24-hour will be ineligible.
- The participant has known hypersensitivity to any of the study interventions or any components in their formulations, any history of anaphylaxis, or recent (within 5 months) history of uncontrollable asthma.
- Prior solid organ transplantation.
- Severe and/or clinically relevant acute or chronic diseases which, in the opinion of the Investigator, might impair the participant’s tolerance for the study or ability to consistently participate in study procedures.
- Participants with current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with participation for the full duration of the study, or is not in the best interest of the participant, in the opinion of the treating Investigator.
- Gastrointestinal malabsorption, GI anastomosis, or any other condition that might affect absorption of lenvatinib.
- Pregnancy or breast feeding.
- Any other active malignancy within the past 2 years of Screening.
- The participant is affected with an autoimmune disease necessitating steroid therapy or other immunomodulatory therapy within the past 2 years of Screening.
- Known active alcohol or drug abuse.
- The participant has received treatment with chemotherapy, differentiation therapy, or other immunotherapy within 3 weeks of study entry.
- The participant has received prior therapy with anti-PD-1, anti-PDL1, anti-CTLA4 or CD137 directed therapy.
- The participant has received prior treatment with lenvatinib or any tyrosine kinase inhibitor.
- Requirement for daily doses of steroids > 8 mg of methylprednisolone (or equivalent).
- The participant is experiencing any nonhematologic toxicity from prior treatment that has not resolved to Grade ≤ 1 per (CTCAE) Version 5.0 at Screening.
- The participant has an active infection necessitating systemic treatment with antibiotics, antifungals, antivirals or steroids within 72 hours of the first dose of study intervention.
- Clinically significant cardiovascular or cerebrovascular disease
- Prior allogeneic stem cell transplant within the last 5 years.
- The participant has received any hematopoietic growth factor within 2 weeks of study entry.
- The participant has received transfusion of packed red blood cells or platelets within 2 weeks before Screening to meet eligibility criteria.
- The participant has interstitial lung disease OR has a history of druginduced pneumonitis.
- The participant has received treatment with live vaccines or live attenuated vaccines within 4 weeks prior to the first dose of avelumab.
- The participant has received treatment with herbal anticancer therapy within 1 week of study entry.
- Prior/Concurrent Clinical Study Experience: The participant has received investigational therapy within 5 halflives or 28 days of study entry.
- Any other reason that, in the opinion of the Investigator, precludes the participant from participating in the study.
- Active hemoptysis (bright red blood of at least 2.5 mL) within 3 weeks prior to the first dose of study interventions.
- Participants with active hepatitis B or hepatitis C infections.
- Participants with known human immunodeficiency virus infection.
- Participants with a serious nonhealing wound, ulcer or bone fracture.
- Participants demonstrating evidence of worsening of neurologic deficit within 1 week prior to initiation of study interventions.
- Participants with bulky tumor
The study team makes the final eligibility decision.
Where it's taking place
- United States
- Korea, Republic of
- Canada
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 0-17 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include United States; Korea, Republic of; Canada. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.