Status:

RECRUITING

Efficacy And Safety Of Hydroxychloroquine Combined With Methotrexate, Capecitabine And Bevacizumab Vs. Regorafenib In Participants With Refractory Metastatic Colorectal Cancer With Mutations In RAS Genes

Lead Sponsor:

Sergey Orlov, MD

Conditions:

Metastatic Colorectal Cancer (mCRC)

Colorectal Neoplasms

Eligibility:

All Genders

18+ years

Phase:

PHASE2

Brief Summary

This study will evaluate efficacy and safety of hydroxychloroquine combined with methotrexate, capecitabine and bevacizumab versus regorafenib in participants with refractory metastatic colorectal can...

Detailed Description

One potential therapeutic option for pretreated patients with RAS-positive metastatic colorectal cancer (mCRC) could be hydroxychloroquine. The KRAS mutation drives uncontrolled proliferation and cell...

Eligibility Criteria

Inclusion

  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
  • Provide written informed consent
  • Age ≥ 18 years
  • Histologically confirmed diagnosis of colorectal cancer (CRC) with distant metastases.
  • Presence of mutations in the KRAS or NRAS gene.
  • Participants must have previously treated for metastatic colorectal cancer and experienced disease progression during receiving at least 2 lines of systemic chemotherapy in combination with antiangiogenic agents.
  • Patient has previously received oxaliplatin- and irinotecan-containing regimens and developed resistance to these chemotherapeutic agents.

Exclusion

  • Presence of clinically significant cardiovascular disease: severe or unstable ischemic heart disease, history of myocardial infarction, New York Heart Association Class III/IV congestive heart failure, ventricular arrhythmias.
  • Stroke and/or transient ischemic attack within 6 months prior to screening;
  • Uncontrolled hypertension
  • History of previous malignancies except non-melanoma skin cancers, or in situ cervical or breast cancer unless a complete remission was achieved at least 2 years prior to randomization AND no additional therapy is required during the study period. Patients having hepatic involvement of cancer should be excluded as per investigator assessment.
  • Patients with CNS metastases are eligible only if the metastases are adequately treated.
  • Absolute neutrophil count (ANC) \<1.5×109/L, platelet count \<100×109/L, or hemoglobin \<9.0 g/dL.
  • Serum total bilirubin \>1.5 × the upper limit of normal (ULN). Participants with Gilbert syndrome, bilirubin \<2 X ULN, and normal AST/ALT are eligible;
  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>3 × ULN;
  • Serum creatinine \>1.5 × ULN.
  • History of a thromboembolic event
  • Presence of any allergic reactions to components of the study drugs
  • Concomitant medications with a known risk of causing QT prolongation and/or Torsades de Pointes.
  • Any anti-cancer systemic therapy, radiation therapy
  • Women who are pregnant or lactating;
  • Presence of unresolved adverse events of grade 2 or higher toxicity, according to CTCAE v5.0 criteria, from prior therapy (except for alopecia or neurotoxicity grade≤2).
  • Any other serious or uncontrolled medical disorder, active infection, physical examination finding, laboratory finding, altered mental status, or psychiatric condition that, in the opinion of the investigator, would limit a patient's ability to comply with the study requirements, substantially increase risk to the patient, or impact the interpretability of study results.

Key Trial Info

Start Date :

March 17 2025

Trial Type :

INTERVENTIONAL

Allocation :

ESTIMATED

End Date :

October 1 2027

Estimated Enrollment :

60 Patients enrolled

Trial Details

Trial ID

NCT06949982

Start Date

March 17 2025

End Date

October 1 2027

Last Update

May 4 2025

Active Locations (1)

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1

First Pavlov State Medical University

Saint Petersburg, Sankt-Peterburg, Russia, 197022