Efficacy, Tolerability and Safety of Intravenous D-VC With ATO in Patients With Advanced/Metastatic Colorectal Cancer

NCT05721872 | Unknown Phase 1 DMC

• 1 other identifier: BR11765589
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

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. 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. 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)

Conditions

Colorectal Cancer; Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (5)

• Change from baseline DV-C levels at 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.

  Baseline, 1 hour

• Change from baseline DV-C levels at 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.

  Baseline, 3 hours

• Change from baseline DV-C levels at 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.

  Baseline, 6 hours

• Change from baseline DV-C levels at 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.

  Baseline, 24 hours

• Response to D-isoascorbic Acid (D-VC) in combination with arsenic trioxide (ATO)

  Objective partial or complete response by RECIST 1.1, confirmed on a second CT scan at least 4 weeks apart

  Baseline, 4 weeks

Secondary Outcomes (4)

• Change from baseline number of participants with treatment-related adverse events as assessed by CTCAE v4.0 at 1 hour

  Baseline, 1 hour

• Change from baseline number of participants with treatment-related adverse events as assessed by CTCAE v4.0 at 3 hours

  Baseline, 3 hours

• Change from baseline number of participants with treatment-related adverse events as assessed by CTCAE v4.0 at 6 hours

  Baseline, 6 hours

• Change from baseline number of participants with treatment-related adverse events as assessed by CTCAE v4.0 at 24 hours

  Baseline, 24 hours

Study Arms (3)

Combination of D-isoascorbic acid (D-VC) with arsenic trioxide (ATO)-Phase 1

EXPERIMENTAL

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.

Combination Product: D-isoascorbic Acid (D-VC) With Arsenic Trioxide (ATO)

Combination of D-isoascorbic acid (D-VC) with arsenic trioxide (ATO)-Phase 2

EXPERIMENTAL

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 Product: D-isoascorbic Acid (D-VC) With Arsenic Trioxide (ATO)

Standard therapy (FOLFOX/FOLFIRI)-Phase 2

ACTIVE COMPARATOR

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

Drug: FOLFOX/FOLFIRI regimen

Interventions

D-isoascorbic Acid (D-VC) With Arsenic Trioxide (ATO) COMBINATION_PRODUCT

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.

Combination of D-isoascorbic acid (D-VC) with arsenic trioxide (ATO)-Phase 1; Combination of D-isoascorbic acid (D-VC) with arsenic trioxide (ATO)-Phase 2

FOLFOX/FOLFIRI regimen DRUG

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

Standard therapy (FOLFOX/FOLFIRI)-Phase 2

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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;

Sponsors & Collaborators

• Nazarbayev University: lead
• National Laboratory Astana: collaborator

Study Sites (1)

Kazakh Institute of Oncology and Radiology

Almaty, 050000, Kazakhstan

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Folfox protocol

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Central Study Contacts

Dos Sarbassov, PhD

CONTACT

+77172705873; nlagen.dir@nu.edu.kz

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2023
• First Posted: February 10, 2023
• Study Start: February 15, 2023
• Primary Completion: August 1, 2023
• Study Completion: November 1, 2023
• Last Updated: February 10, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

KA (1)