Liothyronine + BIT Regimen for Brain Cancer
(PNOC044 Trial)
What You Need to Know Before You Apply
What is the purpose of this trial?
This trial explores a new treatment for children and young adults with medulloblastoma, a type of brain cancer that has returned or worsened after standard treatments. It tests a combination of liothyronine (a thyroid hormone) with a standard chemotherapy regimen known as BIT (bevacizumab, irinotecan, and temozolomide) to determine if it can improve treatment outcomes. Participants who have undergone initial standard treatment for medulloblastoma and are experiencing relapsed or progressive disease may be suitable candidates. The researchers aim to find the best dose and assess the safety and effectiveness of this combined therapy. As a Phase 1 trial, this study focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications, but if you are on levothyroxine, your dose must be stable for at least 3 months before joining. Also, you cannot take medications that strongly affect certain liver enzymes, so check with your doctor about your current meds.
Is there any evidence suggesting that this trial's treatments are likely to be safe?
Research has shown that liothyronine (L-T3) is generally well-tolerated. It may slow tumor growth and help cancer cells mature, making it a potential treatment for medulloblastoma, a type of brain cancer. Some studies suggest that liothyronine's side effects are manageable for patients with brain tumors.
The BIT regimen, which combines bevacizumab, irinotecan, and temozolomide, has proven effective in treating certain cancers. Bevacizumab stops blood vessels from growing in tumors, while irinotecan and temozolomide serve as chemotherapy drugs. Research indicates that this combination is generally well-tolerated, and studies in children have shown it can lower the risk of death in cases of recurring medulloblastoma.
Overall, both liothyronine and the BIT regimen have demonstrated promise in terms of safety and tolerability in previous studies, offering reassurance about their potential use in treating brain cancer.12345Why are researchers excited about this trial's treatments?
Researchers are excited about the Liothyronine + BIT Regimen for brain cancer because it introduces Liothyronine (L-T3), a thyroid hormone, as a potential game-changer. Unlike traditional options like surgery, radiation, and chemotherapy, which often come with significant side effects, L-T3 targets cancer in a novel way by potentially enhancing the effectiveness of the BIT Regimen, which includes Bevacizumab, Irinotecan, and Temozolomide. This combination might help in clearing cancerous cell-free DNA in the cerebrospinal fluid more efficiently, offering new hope for both children and adults with medulloblastoma or relapsed/progressive brain cancer. The unique combination and mode of action could mean faster and more effective results, particularly for those who have exhausted conventional therapies.
What evidence suggests that this trial's treatments could be effective for brain cancer?
Research has shown that liothyronine (L-T3), a thyroid hormone, can slow the growth of medulloblastoma, a common brain cancer in children. It enhances chemotherapy effectiveness, allowing for lower doses of chemo drugs. Studies suggest that L-T3 can also help tumor cells behave more like normal cells. In this trial, participants in the Phase 1 cohort will receive L-T3 with the BIT regimen, which includes bevacizumab, irinotecan, and temozolomide. Research has demonstrated strong results for the BIT regimen, with significant improvements in survival times for patients with medulloblastoma. Together, L-T3 and the BIT regimen offer a promising approach to treating this challenging cancer.13456
Who Is on the Research Team?
Sabine Mueller
Principal Investigator
University of California, San Francisco
Are You a Good Fit for This Trial?
This trial is for children and young adults aged 1-25 with medulloblastoma that has come back or gotten worse after initial treatment. They must have had standard therapy, be in a certain health condition (Karnofsky/Lansky score ≥50), and meet specific blood count and organ function requirements. Some may need to show tumor DNA in their spinal fluid.Inclusion Criteria
Timeline for a Trial Participant
Screening
Participants are screened for eligibility to participate in the trial
Treatment
Participants receive L-T3 in combination with BIT regimen or as monotherapy, with dose escalation to determine RP2D
Follow-up
Participants are monitored for safety and effectiveness after treatment, including cf-DNA clearance and adverse events
Open-label extension (optional)
Participants may continue L-T3 monotherapy for one additional year if benefiting from therapy
What Are the Treatments Tested in This Trial?
Interventions
- BIT Regimen (Bevacizumab, Irinotecan, Temozolomide)
- Liothyronine
Trial Overview
The study tests Liothyronine (L-T3) immunotherapy combined with the BIT chemotherapy regimen (Bevacizumab, Irinotecan, Temozolomide) on those whose medulloblastoma has relapsed or progressed post-standard therapy. It's divided into phases to assess safety and effectiveness.
How Is the Trial Designed?
3
Treatment groups
Experimental Treatment
Children and young adults with medulloblastoma and CSF cf-DNA positivity without radiographic disease progression/recurrence following standard upfront therapy. will include children and young adults with medulloblastoma and positive cf-DNA in CSF following initial standard therapy and will involve a Phase 2 to evaluate clearance of cf-DNA positive disease in CSF in response to L-T3 monotherapy at the RP2D. Cohort 2 will begin enrolling once the RP2D of L-T3 is established.
Participants will be treated at the RP2D of L-T3 based on the results of the safety Phase 1 cohort. Participants may continue therapy for up to 12 cycles if there is no evidence of unacceptable toxicity, disease progression, or withdrawal of consent. For participants that are benefiting from therapy, they may continue L-T3 monotherapy for one additional year (24 cycles total therapy). Treatment beyond that specified in the protocol should be discussed with the study chairs. Duration of Follow up Participants will enter follow up after the 30-day toxicity period. Follow-up procedures are to be captured under the PNOC COMP protocol with the exception of protocol defined follow up procedures. Participants will be followed under the PNOC COMP protocol until death or withdrawal from study.
Participants will be treated with a backbone of BIT. L-T3 will be administered on day 1 of each cycle at planned dose levels (DL). Once the Recommended Phase 2 Dose (RP2D) is established with dosing days 1-7, an additional cohort of 6 participants will be treated at the maximum tolerated DL for 14 days of the cycle, Dose level escalation (DLE), which, if tolerated, will become the RP2D. If DLE is not tolerated, the RP2D will become the highest tolerated DL from the prior cohort.
Find a Clinic Near You
Who Is Running the Clinical Trial?
Sabine Mueller, MD, PhD
Lead Sponsor
Citations
Efficacy and safety of bevacizumab, irinotecan ...
Results: The complete and partial objective response rates were 66.6% in patients with medulloblastoma and 75.0% in patients with AT/RT or CNS ...
Efficacy and safety of bevacizumab, irinotecan, and ...
The 12- and 24-month OS rates were high at 67.1% and 58.7%, respectively. The tendency for longer PFS and OS may have resulted from a better ...
Bevacizumab, irinotecan, and temozolomide with re- ...
This is the first case report of an adult with recurrent MB treated with BEV, IRI, TMZ, and re-irradiation. This regimen was deemed safe and thus may be an ...
Temozolomide with irinotecan versus ... - PubMed Central
The addition of bevacizumab to TMZ/irinotecan significantly reduced the risk of death and an EFS-event in children with recurrent MB. The combination was ...
Phase II study of the combination of bevacizumab plus ...
Methods: We completed a phase II study to evaluate tumor responses to BIT in patients with measurable/evaluable refractory or relapsed high-risk ...
Bevacizumab, Irinotecan and Temozolomide for Relapsed ...
The purpose of this study is to find how good and how safe the combination of irinotecan, temozolomide and bevacizumab is for patients with resistant or ...
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