Combining hydroxychloroquine with chemotherapy for advanced colorectal cancer
A Randomized Trial To Compare Efficacy And Safety Of Hydroxychloroquine Combined With Methotrexate, Capecitabine And Bevacizumab Versus Regorafenib In Participants With Refractory Metastatic Colorectal Cancer With Mutations In RAS Genes
This study is testing if adding hydroxychloroquine to standard chemotherapy can help people with advanced colorectal cancer live longer and feel better.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 60 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Pavlov First Saint Petersburg State Medical University Academic / other |
| Drugs / interventions | chemotherapy, radiation, bevacizumab, methotrexate, trametinib |
| Locations | 1 site (Saint Petersburg, Sankt-Peterburg) |
| Trial ID | NCT06949982 on ClinicalTrials.gov |
What this trial studies
This study evaluates the efficacy and safety of a combination treatment involving hydroxychloroquine, methotrexate, capecitabine, and bevacizumab compared to regorafenib in patients with refractory metastatic colorectal cancer harboring RAS mutations. The research aims to determine if this combination can prolong progression-free and overall survival, as well as improve response rates and disease control. The approach is based on the understanding that hydroxychloroquine can inhibit autophagy, a mechanism that allows cancer cells to survive under stress, thereby enhancing the effectiveness of chemotherapy. Participants will be closely monitored for safety and treatment outcomes.
Who should consider this trial
Good fit: Ideal candidates are adults aged 18 and older with histologically confirmed metastatic colorectal cancer and RAS mutations who have previously undergone at least two lines of systemic chemotherapy.
Not a fit: Patients with significant cardiovascular disease or those who have not previously received specific chemotherapy regimens may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could provide a new effective option for patients with difficult-to-treat metastatic colorectal cancer.
How similar studies have performed: Previous studies have shown promising results with hydroxychloroquine in combination with other therapies for similar conditions, indicating potential for success in this approach.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * 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 Criteria: * 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.
Where this trial is running
Saint Petersburg, Sankt-Peterburg
- First Pavlov State Medical University — Saint Petersburg, Sankt-Peterburg, Russia (Recruiting)
Study contacts
- Study coordinator: Sergey V. Orlov, Professor
- Email: orloff-sv@mail.ru
- Phone: +79811957915
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.