Hydroxychloroquine Combined With Gemcitabine in the Treatment of Advanced Non-small Cell Lung Cancer

Phase II Clinical Study of Hydroxychloroquine Combined With Gemcitabine in the Treatment of Advanced Non-small Cell Lung Cancer

To evaluate the efficacy and safety of hydroxychloroquine (600mgBID) combined with gemcitabine (1000mg/m2,d1,8) in the third-line and above treatment of advanced NSCLC.

Study Overview

• Status: Not yet recruiting
• Conditions: Lung Neoplasms; Gemcitabine; Hydroxychloroquine
• Intervention / Treatment: Drug: Hydroxychloroquine Combined With Gemcitabine

Detailed Description

This study is a single-arm, open phase II prospective cohort study to evaluate the efficacy and safety of hydroxychloroquine (600mgBID) combined with gemcitabine in the treatment of advanced NSCLC patients with third-line and above treatment. After signing informed consent, the subjects were screened and eligible for inclusion in this study.

All enrolled subjects will be treated with (hydroxychloroquine 600mgBID) plus gemcitabine, and each patient will continue to receive the study drug until the end of the treatment cycle. The efficacy index and safety index were observed during the treatment.

1. Hydroxychloroquine sulfate tablets: twice a day, each time (600mg). Continuous oral administration. Until the disease progresses or becomes intolerable.
2. gemcitabine was administered intravenously at a dose of 1000mg/m2 for 30min,d1, 8, and every 3 weeks (21 days) until disease progression or intolerable toxicity, with a maximum duration of 2 years.

• Study Type: Interventional
• Enrollment (Anticipated): 55
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients must have histologically or cytologically proven advanced lung squamous cell carcinoma or lung adenocarcinoma with negative EGFR and ALK gene mutations.
• Patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria, meaning that at least one lesion can be accurately measured by conventional techniques of CT or MRI.
• It is acceptable for patients who have received radiotherapy. It must be at least 4 months after radiotherapy, and all signs of toxicity must abate.
• The patient must be 18 years of age or above.
• The ECOG performance status of patients must be 0-1.
• Patients should not become pregnant or breastfeed because chemotherapy is considered to pose significant risks to the fetus/baby.
• The patient must have a life expectancy of more than three months.
• Patients must be able to understand and willing to sign written informed consent.
• Previously received systematic treatment with 2 regimens;
• Treatment with hydroxychloroquine sulfate tablets plus gemcitabine is required to be initiated within 28 days after informed consent;

• The function of vital organs should meet the following requirements as far as possible (if laboratory test values do not meet the following criteria, they can also be included in the registration after comprehensive evaluation by researchers) :

  1. Absolute neutrophil count ≥1.5×109/L;
  2. Platelets ≥80×109/L;
  3. Hemoglobin ≥9g/dL;
  4. Serum albumin ≥ 3G /dL;
  5. Total bilirubin ≤1.25×ULN;
  6. ALT and AST ≤2.5×ULN; If liver metastases were present, ALT and AST≤5×ULN;
  7. serum creatinine ≤1.25×ULN or creatinine clearance ≥50mL/min.

Exclusion Criteria:

• Patients with rapid progression after 1 or 2 cycles in first-line and second-line regimens.
• Persons with known allergies or metabolic disorders to any drug in the treatment regimen.
• Patients who had previously received hydroxychloroquine.
• Patients with known G6PD deficiency, severe psoriasis, porphyria, macular degeneration, or severe diabetic retinopathy were ineligible because of the potential for greater hydroxychloroquine toxicity.
• Symptomatic central nervous metastasis. Patients with asymptomatic brain metastases or stable brain metastases after treatment were eligible to participate in the study if they met all the following criteria: measurable lesions outside the central nervous system; No mesencephalon, pons, cerebellum, meninges, medulla oblongata or spinal cord metastases; Maintain clinical stability for at least 2 weeks.
• A history of psychotropic drug abuse, alcoholism or drug abuse;
• In the 6 months prior to study entry, the following conditions occurred: myocardial infarction, severe/unstable angina pectoris, New York Heart Association (NYHA) grade 2 or higher cardiac dysfunction, and poorly controlled arrhythmias (including QT c F interval men & GT; 450 m s, female & GT; 470 ms, QT cF interval calculated by Fridericia formula), symptomatic congestive heart failure, cerebrovascular accident (including transient ischemic attack or symptomatic pulmonary embolism);
• Human immunodeficiency virus (HIV, HIV 1/2 antibody) positive; Acute or chronic active hepatitis B (HBsAg positive and HBV DNA & g t; 1*103/ml) or acute or chronic active hepatitis C (HCV antibody positive and HCV RNA & g t; 15 iu/ml); Active pulmonary tuberculosis;
• Other factors that may affect patient safety or compliance as determined by the investigator. If there is a serious illness (including mental illness) that requires concomitant treatment, serious laboratory abnormalities, or other family or social factors.
• Patients deemed inappropriate for enrollment by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Hydroxychloroquine combined with gemcitabine; Hydroxychloroquine sulfate tablets: twice a day, each time (600mg). Continuous oral administration. Until the disease progresses or becomes intolerable.; gemcitabine was administered intravenously at a dose of 1000mg/m2 for 30min,d1, 8, and every 3 weeks (21 days) until disease progression or intolerable toxicity, with a maximum duration of 2 years.

Drug: Hydroxychloroquine Combined With Gemcitabine; Hydroxychloroquine combined with chemotherapy; Other Names: chloroquine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate(ORR)	The proportion of patients whose tumor volume reduction reaches the predetermined value and can maintain the minimum time limit is the sum of the proportion of complete and partial remission.	1years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease control rate(DCR)	The percentage of patients with PR + Cr and SD after treatment in the number of evaluable cases, and the RECIST standard is at least 4 weeks	2 years
Progression-free survival(PFS)	The time between initiation of the study drug and the first recorded date of disease progression (PD) or death, depending on which occurred first. If no disease progression is observed, the cutoff date should be the date of the last tumor measurement.	2 years
Overall survival(OS)	The time from the beginning of treatment to (for any reason) death. The last follow-up time is usually calculated as the time of death for the subjects who have lost the visit before death	2 years

Collaborators and Investigators

• Sponsor: Henan Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): December 15, 2022
• Primary Completion (Anticipated): October 1, 2024
• Study Completion (Anticipated): October 1, 2025

Study Registration Dates

• First Submitted: September 15, 2022
• First Submitted That Met QC Criteria: December 3, 2022
• First Posted (Estimate): December 12, 2022

Study Record Updates

• Last Update Posted (Estimate): December 12, 2022
• Last Update Submitted That Met QC Criteria: December 3, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Amebicides; Gemcitabine; Chloroquine; Hydroxychloroquine
• Other Study ID Numbers: 2022213

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No