Efficacy, Tolerability and Safety of Intravenous D-VC With ATO in Patients With Advanced/Metastatic Colorectal Cancer
- Conditions
- Colorectal CancerMetastatic Colorectal Cancer
- Interventions
- Drug: FOLFOX/FOLFIRI regimenCombination Product: D-isoascorbic Acid (D-VC) With Arsenic Trioxide (ATO)
- Registration Number
- NCT05721872
- Lead Sponsor
- Nazarbayev University
- Brief Summary
The goal of this exploratory phase I/II single-center clinical trial is to evaluate effectiveness, tolerability, and safety of Intravenous D-isoascorbic Acid (D-VC) With Arsenic Trioxide in Patients With Advanced/Metastatic Colorectal Cancer Who Have Exhausted Standard Therapy The main questions are to learn about effectiveness, tolerability, and safety of Intravenous D-isoascorbic Acid (D-VC) With Arsenic Trioxide.
The study aims to:
1. Assess the tolerability and pharmacokinetics of D-isoascorbic acid (D-VC) with a single intravenous injection in the monotherapy regimen and in the sequential administration regimen with arsenic trioxide (ATO) in patients on standard therapy for advanced/metastatic malignancies (Phase I)
2. Evaluate the efficacy and safety of D-isoascorbic acid (D-VC) with repeated intravenous administration in the mode of sequential administration with arsenic trioxide (ATO) in patients who have exhausted standard therapy for advanced/metastatic colorectal cancer (Phase II)
In phase I participants will receive single intravenous administration as monotherapy of D-isoascorbic acid (D-VC) with dose escalation (0.05, 0.1, 0.2 g/kg/day) and with arsenic trioxide (ATO).
Patients who have satisfactorily tolerated the study drug in combination with arsenic trioxide (ATO) in a phase I study are transferred to a phase II clinical trial.
To study the safety and efficacy of the study drug in phase II, D-VC after the administration of ATO will be implemented in 2 groups:
Study group 1: ATO (at a dose of 0.15 mg / kg / day) after intravenous administration after 2 hours D-VC intravenously once a day at the maximum tolerated dose, determined at the end of phase I for at least 15 patients.
Group 2 standard therapy: 15 patients.
For the phase I researchers will compare laboratory tests (including clinical biochemistry and hematology), vital signs, clinical adverse events (diseases, symptoms and complaints) and other specific safety tests (for example, an electrocardiogram, ophthalmic examination) between groups. They will also measure the degree to which overt adverse reactions can be subjectively tolerated by the subject of the study.
For the phase II researchers will compare degrees of tumor volume reduction on CT; objective response rate (ORR) based on BICR according to RECIST v1.1 between test and standard therapy groups. They will also continue evaluation of safety and tolerability of ATO + D-VC combination therapy.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 38
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Standard therapy (FOLFOX/FOLFIRI)-Phase 2 FOLFOX/FOLFIRI regimen Drug: FOLFOX/FOLFIRI regimen FOLFOX - oxaliplatin 85mg/m2 1 day, Leucovorin 200mg/m2 IV 2h, 1, 2 days, 5 - Fluorouracil 400mg/m2 IV bolus, 1, 2 days, 5 - Fluorouracil 600mg/m2 IV 22h, 1, 2 days FOLFIRI - Irinotecan 180 mg/m2 IV, Leucovorin 400 mg/m2 IV, Fluorouracil bolus 400 mg/m2 IV, Fluorouracil infusional 2400 mg/m2 IV. Courses are held every 2 weeks Combination of D-isoascorbic acid (D-VC) with arsenic trioxide (ATO)-Phase 2 D-isoascorbic Acid (D-VC) With Arsenic Trioxide (ATO) After 2 hours of intravenous administration of arsenic trioxide (ATO) (at a dose of 0.15 mg / kg / day) participants will further receive D-isoascorbic acid (D-VC) intravenously once a day at the maximum tolerated dose, determined at the end of phase I. Combination of D-isoascorbic acid (D-VC) with arsenic trioxide (ATO)-Phase 1 D-isoascorbic Acid (D-VC) With Arsenic Trioxide (ATO) Participants will receive single intravenous administration as monotherapy of D-isoascorbic acid (D-VC) with dose escalation (0.05, 0.1, 0.2 g/kg/day) and with arsenic trioxide (ATO). Patients who have satisfactorily tolerated the study drug in combination with arsenic trioxide (ATO) in a phase I study are transferred to a phase II clinical trial.
- Primary Outcome Measures
Name Time Method Change from baseline DV-C levels at 1 hour Baseline, 1 hour Patients who have satisfactorily tolerated D-isoascorbic Acid (D-VC) in combination with arsenic trioxide (ATO) in a phase I study are transferred to a phase II clinical trial.
Change from baseline DV-C levels at 3 hours Baseline, 3 hours Patients who have satisfactorily tolerated D-isoascorbic Acid (D-VC) in combination with arsenic trioxide (ATO) in a phase I study are transferred to a phase II clinical trial.
Change from baseline DV-C levels at 6 hours Baseline, 6 hours Patients who have satisfactorily tolerated D-isoascorbic Acid (D-VC) in combination with arsenic trioxide (ATO) in a phase I study are transferred to a phase II clinical trial.
Change from baseline DV-C levels at 24 hours Baseline, 24 hours Patients who have satisfactorily tolerated D-isoascorbic Acid (D-VC) in combination with arsenic trioxide (ATO) in a phase I study are transferred to a phase II clinical trial.
Response to D-isoascorbic Acid (D-VC) in combination with arsenic trioxide (ATO) Baseline, 4 weeks Objective partial or complete response by RECIST 1.1, confirmed on a second CT scan at least 4 weeks apart
- Secondary Outcome Measures
Name Time Method Change from baseline number of participants with treatment-related adverse events as assessed by CTCAE v4.0 at 1 hour Baseline, 1 hour Adverse events in patients will be assessed by CTCAE v4.0
Change from baseline number of participants with treatment-related adverse events as assessed by CTCAE v4.0 at 3 hours Baseline, 3 hours Adverse events in patients will be assessed by CTCAE v4.0
Change from baseline number of participants with treatment-related adverse events as assessed by CTCAE v4.0 at 6 hours Baseline, 6 hours Adverse events in patients will be assessed by CTCAE v4.0
Change from baseline number of participants with treatment-related adverse events as assessed by CTCAE v4.0 at 24 hours Baseline, 24 hours Adverse events in patients will be assessed by CTCAE v4.0
Trial Locations
- Locations (1)
Kazakh Institute of Oncology and Radiology
🇰🇿Almaty, Kazakhstan