Trial Title:
Efficacy, Tolerability and Safety of Intravenous D-VC With ATO in Patients With Advanced/Metastatic Colorectal Cancer
NCT ID:
NCT05721872
Condition:
Colorectal Cancer
Metastatic Colorectal Cancer
Conditions: Official terms:
Colorectal Neoplasms
Arsenic Trioxide
Isoascorbic acid
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Combination Product
Intervention name:
D-isoascorbic Acid (D-VC) With Arsenic Trioxide (ATO)
Description:
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.
Phase 1 - Scheme 1 - single intravenous administration in monotherapy with dose
escalation (0.05, 0.1, 0.15 g/kg/day); Scheme 2 - single intravenous administration in
the mode of sequential administration with arsenic trioxide with dose escalation of
D-isoascorbic acid (0.05, 0.1, 0.15 g/kg/day).
Phase 2 - Study group 1: 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 for at least 15 patients.
Arm group label:
Combination of D-isoascorbic acid (D-VC) with arsenic trioxide (ATO)-Phase 1
Arm group label:
Combination of D-isoascorbic acid (D-VC) with arsenic trioxide (ATO)-Phase 2
Intervention type:
Drug
Intervention name:
FOLFOX/FOLFIRI regimen
Description:
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
Arm group label:
Standard therapy (FOLFOX/FOLFIRI)-Phase 2
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.
Criteria for eligibility:
Criteria:
Phase 1:
INCLUSION CRITERIA:
- informed consent to participate in the study
- patients of the second clinical group with malignant neoplasms of a
common/metastatic form that have exhausted standard therapy.
- patients who have received at least 3 lines of standard therapy, including those
with the use of targeted drugs, patients who have exhausted the possibilities of
using specialized drugs, as part of the recommendations of treatment protocols
- the presence of "+" KRAS / NRAS status of the primary tumor or metastatic focus
(determined in LEKzone 2, codons 12, 13, 61)
- ≥1 measurable lesion defined by RECIST v1.1
- ECOG PS 0.1 or 2
EXCLUSION CRITERIA:
- age up to 18 years
- pregnancy and lactation
- patients with an autoimmune disease or with a medical diagnosis requiring systemic
immunosuppression
- decompensated diabetes mellitus
- renal failure, urolithiasis
- diabetes
- thrombophlebitis, tendency to thrombosis
- severe lung disease, dyspnea at rest, pleural effusion
- cardiovascular insufficiency, ejection fraction of the heart <40%
- sensory neuropathy of the 1st degree of any etiology
- uncontrolled infections
- persons from the category of "vulnerable patients" (homeless, military personnel,
incapacitated, patients in emergency conditions, other persons who may be subjected
to pressure);
- Allergy in history and during screening (drug, pollen, etc.);
- participation in any other clinical trial;
- hypersensitivity to arsenic;
- individual intolerance to ascorbic acid;
- thrombophlebitis and thrombosis, a tendency to thrombosis in history;
- increased blood clotting and pathologies associated with this deviation;
- diabetes;
- nephrolithiasis or nephrolithiasis;
- the patient does not agree to perform the procedures required by the protocol and is
unable to adhere to the schedule of procedures.
- if the patients have any other laboratory or other abnormalities, in the opinion of
the Investigator, that can harm the patients and the results of the study.
Phase II:
INCLUSION CRITERIA:
for both groups (30 patients, considering 20% decrease from the study):
- informed consent to participate in the study
- patients of the second clinical group with advanced/metastatic colorectal cancer
- Patients must have previously received at least 3 lines of standard drug therapy,
including those with the use of targeted drugs, who have exhausted the possibilities
of using specialized drugs, as part of the recommendations of colorectal cancer
treatment protocols - the presence of "+" KRAS / NRAS status of the primary tumor,
or metastatic focus (determined in exon 2, codons 12, 13, 61)
- ≥1 measurable lesion defined by RECIST v1.1
- ECOG PS 0.1 or 2
EXCLUSION CRITERIA:
- age up to 18 years
- patients with an autoimmune disease or with a medical diagnosis requiring systemic
immunosuppression
- decompensated diabetes mellitus
- renal failure, urolithiasis
- thrombophlebitis, tendency to thrombosis
- severe lung disease, dyspnea at rest, pleural effusion
- cardiovascular insufficiency, ejection fraction of the heart <40%
- sensory neuropathy of the 1st degree of any etiology
- uncontrolled infections
- persons from the category of "vulnerable patients" (homeless, military personnel,
incapacitated, patients in emergency conditions, other persons who may be subjected
to pressure);
- Allergy in history and during screening (drug, pollen, etc.);
- participation in any other clinical trial;
- hypersensitivity to arsenic;
- individual intolerance to ascorbic acid;
- thrombophlebitis and thrombosis, a tendency to thrombosis in history;
- increased blood clotting and pathologies associated with this deviation;
- diabetes;
- nephrolithiasis or nephrolithiasis;
- the patient does not agree to perform the procedures required by the protocol and is
unable to adhere to the schedule of procedures.
- if the patients have any other laboratory or other abnormalities, in the opinion of
the Investigator, that can harm the patients and the results of the study.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Kazakh Institute of Oncology and Radiology
Address:
City:
Almaty
Zip:
050000
Country:
Kazakhstan
Status:
Recruiting
Contact:
Last name:
Kaldygul Smagulova, MD, PhD
Phone:
+7-727-292-77-55
Email:
kazior@onco.kz
Start date:
February 15, 2023
Completion date:
November 2023
Lead sponsor:
Agency:
Nazarbayev University
Agency class:
Other
Collaborator:
Agency:
National Laboratory Astana
Agency class:
Other
Source:
Nazarbayev University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05721872
