DAY101 vs. Standard of Care Chemotherapy in Pediatric Patients With Low-Grade Glioma Requiring First-Line Systemic Therapy (LOGGIC/FIREFLY-2)
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| ClinicalTrials.gov Identifier: NCT05566795 |
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Recruitment Status :
Recruiting
First Posted : October 4, 2022
Last Update Posted : May 2, 2024
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Low-grade Glioma | Drug: Tovorafenib Drug: Chemotherapeutic Agent | Phase 3 |
Approximately 400 treatment-naïve low-grade glioma patients will be randomized 1:1 to either tovorafenib (Arm 1) or an Investigator's choice of SoC chemotherapy (Arm 2).
Arm 1 (tovorafenib): treatment cycles will repeat every 28 days in the absence of disease progression. Patients will continue tovorafenib until any of the following occurs: disease progression based on Response Assessment in Neuro-Oncology (RANO-LGG) criteria, unacceptable toxicity, withdrawal of consent to treatment, or end of study.
Arm 2 (Investigator's Choice of SoC Chemotherapy): patients will receive one of 3 SoC chemotherapy options selected by the treating Investigator: Children's Oncology Group - Vincristine/Carboplatin (COG-V/C) regimen, International Society for Paediatric Oncology - Low-Grade Glioma Vincristine/Carboplatin (SIOPe-LGG-V/C) regimen, or vinblastine (VBL) regimen. The choice of SoC chemotherapy regimen will be selected prior to patient randomization. Treatment will continue until completion of therapy or until any of the following occurs: disease progression based on RANO-LGG criteria, unacceptable toxicity, withdrawal of consent to treatment, or end of study.
Patients who discontinue treatment due to disease progression will have (1) radiographic evidence of progressive disease based on RANO-LGG, as determined by the Investigator and confirmed by the IRC, or (2) clinical progression based on RANO-LGG criteria determined by the Investigator. Investigators are encouraged to discuss cases of clinical progression and early radiographic progression without clinical symptom with the Sponsor Medical Monitor prior to treatment discontinuation or initiation of a different form of treatment for the malignancy. Patients may continue therapy beyond progressive disease
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 400 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | Tovorafenib versus standard of care chemotherapy |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | LOGGIC/FIREFLY-2: A Phase 3, Randomized, International Multicenter Trial of DAY101 Monotherapy Versus Standard of Care Chemotherapy in Patients With Pediatric Low-Grade Glioma Harboring an Activating RAF Alteration Requiring First-Line Systemic Therapy |
| Actual Study Start Date : | February 27, 2023 |
| Estimated Primary Completion Date : | February 2026 |
| Estimated Study Completion Date : | March 2030 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Arm #1
Tovorafenib
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Drug: Tovorafenib
Oral pan-RAF inhibitor
Other Name: DAY101, Ojemda |
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Active Comparator: Arm #2
Investigator's choice of one of the following current standard of care for pediatric patients with low-grade gliomas:
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Drug: Chemotherapeutic Agent
Intravenous solution for injection
Other Names:
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- Compare the objective response rate (ORR) assessed per RANO-LGG criteria by Independent Review Committee (IRC) of tovorafenib monotherapy versus standard of care (SoC) chemotherapy [ Time Frame: Up to 60 months ]ORR, per RANO-LGG criteria, defined as the proportion of patients with overall confirmed response of complete response (CR) or partial response (PR)
- Compare the progression-free survival (PFS) assessed by IRC of tovorafenib monotherapy versus SoC chemotherapy per RANO-LGG criteria [ Time Frame: Up to 60 months ]PFS per RANO-LGG criteria, defined as time from randomization to PD or death from any cause
- Compare the duration of response (DOR) assessed by IRC of tovorafenib monotherapy versus SoC chemotherapy per RANO-LGG criteria [ Time Frame: Up to 60 months ]DOR per RANO-LGG criteria, defined as time from confirmed response to PD or death from any cause for patients with confirmed response
- Compare the overall survival (OS) of tovorafenib monotherapy versus SoC chemotherapy [ Time Frame: Up to 60 months ]OS, defined as time from randomization up to death from any cause
- Compare the safety and tolerability of tovorafenib monotherapy versus SoC chemotherapy [ Time Frame: Up to 60 months ]Type, frequency, and severity of treatment-emergent adverse events
- Compare the safety and tolerability of tovorafenib monotherapy versus SoC chemotherapy [ Time Frame: Up to 60 months ]Measured by incidence of clinically significant laboratory abnormalities
- Evaluate changes in neurological function and adaptive behavior between tovorafenib versus SoC [ Time Frame: Up to 60 months ]Change from baseline in the Vineland Adaptive Behavior Composite Scales [age-adjusted standard scores range between 20 to 140, with a mean of 100 and standard deviation of 15, and lower scores indicate worse functional outcomes]
- Compare changes in visual function outcomes of tovorafenib monotherapy versus SoC chemotherapy in patients with optic pathway glioma (OPG) [ Time Frame: Up to 60 months ]Measured by Teller Acuity Cards® or alternative
- Compare the ORR of tovorafenib monotherapy versus SoC chemotherapy as assessed by IRC per RANO-HGG, RANO-LGG and Response Assessment in Pediatric Neuro-Oncology (RAPNO-LGG) criteria [ Time Frame: Up to 60 months ]ORR, defined as the proportion of patients with overall confirmed response per RANO-HGG, RANO-LGG, or RAPNO-LGG criteria.
- Compare the clinical benefit rate (CBR) of tovorafenib monotherapy versus SoC chemotherapy as assessed by IRC per RANO-LGG, RANO-HGG and RAPNO-LGG criteria [ Time Frame: Up to 60 months ]CBR, defined as the proportion of patients with radiological tumor stabilization or regression per RANO-LGG, RANO-HGG or RAPNO-LGG criteria, as applicable
- Compare time to response (TTR) of tovorafenib monotherapy versus SoC chemotherapy as assessed by IRC per RANO-LGG, RANO-HGG and RAPNO-LGG criteria [ Time Frame: Up to 60 months ]Measured by the time to first response following initiation of therapy in patients with best overall confirmed response per RANO-LGG, RANO-HGG or RAPNO-LGG criteria, as applicable
- Compare the PFS of tovorafenib monotherapy versus SoC chemotherapy as assessed by IRC per RAPNO-LGG and RANO-HGG criteria [ Time Frame: Up to 60 months ]PFS per RANO-HGG or RAPNO-LGG (as applicable), defined as time from randomization to progressive disease (PD) or death from any cause
- Compare the DOR of tovorafenib monotherapy versus SoC chemotherapy as assessed by IRC per RAPNO-LGG and RANO-HGG criteria [ Time Frame: Up to 60 months ]DOR, defined as time from confirmed response to PD or death from any cause for patients with confirmed response per RANO or RAPNO criteria, as applicable
- Evaluate the health-related quality of life (HRQoL) in tovorafenib versus SoC chemotherapy using Patient-Reported Outcomes Measurement Information System (PROMIS) test battery [ Time Frame: Up to 60 months ]Measured by change from baseline in Total Score at 1, 2, 5 years
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| Ages Eligible for Study: | up to 25 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Less than 25 years of age with LGG with known activating RAF alteration
- Histopathologic diagnosis of glioma or glioneuronal tumor
- At least one measurable lesion as defined by RANO criteria
- Meet indication for first-line systemic therapy
Exclusion Criteria:
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Patient has any of the following tumor-histological findings:
- Schwannoma
- Subependymal giant cell astrocytoma (Tuberous Sclerosis)
- Diffuse intrinsic pontine glioma, even if histologically diagnosed as World Health Organization (WHO) Grade I-II
- Patient's tumor has additional pathogenic molecular alterations
- Known or suspected diagnosis of neurofibromatosis Type 1 or 2 (NF-1/NF-2)
- Prior or ongoing nonsurgical anticancer therapy for this indication (eg, chemotherapy, oral/intravenous targeted therapy) including radiation
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05566795
| Contact: Day One Clinical Trials Information | 650-484-0899 | clinicaltrials@dayonebio.com |
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| Responsible Party: | Day One Biopharmaceuticals, Inc. |
| ClinicalTrials.gov Identifier: | NCT05566795 |
| Other Study ID Numbers: |
DAY101-002 |
| First Posted: | October 4, 2022 Key Record Dates |
| Last Update Posted: | May 2, 2024 |
| Last Verified: | April 2024 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Glioma Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type |
Neoplasms Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Antineoplastic Agents |