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Neoadjuvant Therapy Combined With Radical Surgery for the Treatment of Small Cell Lung Cancer (SCLC) in II and IIIA Stage

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ClinicalTrials.gov Identifier: NCT03523234
Recruitment Status : Recruiting
First Posted : May 14, 2018
Last Update Posted : May 14, 2018
Sponsor:
Information provided by (Responsible Party):
Peng Zhang, Shanghai Pulmonary Hospital, Shanghai, China

Brief Summary:

The main purpose of this study is to compare the effects of neoadjuvant with radical surgery on the prognosis of patients with stage II and IIIA small cell lung cancer (SCLC). The primary endpoint of this study is to observe 5-year survival, disease-free survival (DFS), and overall survival (OS) in patients. Secondary efficacy indicators include recurrence rate, surgical complications, resection rate, quality of life (QoL), and exploration biomarker (tumor tissue).

This is a two-arm, open, multicentral clinical study designed to assess the disease-free survival (DFS) and overall survival (OS) of neoadjuvant chemotherapy plus radical surgery for stage II and IIIA small cell lung cancer (SCLC). About 300 patients will be enrolled in the study and randomly divided into two groups of 150 individuals. The neoadjuvant with radical surgery group received 2 to 4 cycles of neoadjuvant treatment with etoposide plus cisplatin/carboplatin before receiving radical surgery, followed by 2 to 4 cycles of adjuvant chemotherapy (etoposide with cisplatin/carboplatin) plus radiotherapy. Patients in the control group are planned to receive 4 to 6 courses of etoposide plus cisplatin/carboplatin for chemotherapy and radiotherapy.


Condition or disease Intervention/treatment Phase
Small-cell Lung Cancer Drug: neoadjuvant chemotherapy Procedure: radical surgery for stage II and IIIA small cell lung cancer (SCLC) Procedure: prophylactic cranial irradiation Drug: Chemotherapy Not Applicable

Detailed Description:

Before chemotherapy is widely used in clinical work, surgery is the main method for the treatment of lung cancer. However, the prognosis of patients with small cell lung cancer (SCLC) is significantly worse than that of other histological types of lung cancer. The only two prospective studies comparing the surgery with other treatments (surgery vs. radiotherapy alone; induction chemotherapy + surgery vs. chemotherapy + radiotherapy) found that patients in surgery group had a poorer prognosis. Thus, small cell lung cancer was determined to be a non-surgically treated disease. Therefore, for patients with stage II and III A SCLC, combined radiotherapy and chemotherapy are currently recommended. The first-line chemotherapy regimens are etoposide plus cisplatin and carboplatin. Surgical treatment is currently only recommended for very early stage SCLC (T1-2N0M0) with postoperative adjuvant chemotherapy, but these patients only account for about 5% of all SCLC patients. Despite the sensitivity to chemotherapy, the long-term survival of small cell lung cancer remains unsatisfactory. For patients with limited SCLC, even if combined with local radiotherapy, there are still 1/4 to 1/3 of patients progressing due to recurrence of local lesions. So the status of surgical treatment is expected to be reassessed. In recent years, retrospective analysis results of some large databases in Europe and the United States have provided a basis for the role of surgery in the treatment of small cell lung cancer (SCLC). It is believed that surgery should be used as one of the treatment options for SCLC. Based on the results of prospective studies and retrospective studies, a well-designed, phased, prospective study is urgently needed to explore the role of surgery in the treatment of SCLC.

In neoadjuvant therapy combined with radical surgery, neoadjuvant chemotherapy is based on the combination of etoposide and cisplatin/carboplatin. Doses of the drugs are taken from the NCCN guideline for the recommended adjuvant chemotherapy for the limited-period SCLC: namely etoposide 120 mg/m2 through intravenous infusion on Day 1, 2, and 3; cisplatin 60 mg/m2 through intravenous infusion on Day 1 (or carboplatin where area under the curve AUC = 5-6); 4 weeks for a cycle, with a total of 2 cycles of neoadjuvant chemotherapy. Radical surgery is performed according to the growth of SCLC patients after neoadjuvant chemotherapy, using lobectomy or pneumonectomy combined with mediastinal lymph node dissection or sampling. 4 weeks after surgery, chemotherapy and concurrent radiotherapy will be performed. The chemotherapy regimen is the same with that of neoadjuvant chemotherapy, with 4 weeks as a cycle and a total of 2 to 4 cycles. Radiotherapy and adjuvant chemotherapy are planned to be started synchronously, the patients whose intraoperative pathology showed no lymph node metastasis (N0) will receive prophylactic brain irradiation (PCI) treatment and adjuvant chemotherapy synchronously. Within 10 days, the patients will receive a total dose of 25 Gy of PCI, once a day, 2.5 Gy of brain irradiation each time. The patients whose intraoperative pathology show that there is lymph node metastasis (N1-2) are planned to receive PCI combined with mediastinal radiation therapy: namely the patient receive a total of 45 Gy within 3 weeks at the start of adjuvant chemotherapy, twice a day, 1.5 Gy of chest irradiation each time, and the PCI treatment is the same with patients whose intraoperative pathology show there is no lymph node metastasis (N0).


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Neoadjuvant Therapy Combined With Radical Surgery for the Treatment of Small Cell Lung Cancer (SCLC) in II and IIIA Stage
Estimated Study Start Date : June 2018
Estimated Primary Completion Date : July 2018
Estimated Study Completion Date : July 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: surgery group Drug: neoadjuvant chemotherapy
etoposide with cisplatin/carboplatin, undergoing in prior to the surgery

Procedure: radical surgery for stage II and IIIA small cell lung cancer (SCLC)
Lobectomy/total lung resection plus mediastinal lymph node dissection.

Procedure: prophylactic cranial irradiation
prophylactic cranial irradiation (PCI) undergoing with adjuvant chemotherapy simultaneously

Drug: Chemotherapy
etoposide with cisplatin/carboplatin

Placebo Comparator: control group Procedure: prophylactic cranial irradiation
prophylactic cranial irradiation (PCI) undergoing with adjuvant chemotherapy simultaneously

Drug: Chemotherapy
etoposide with cisplatin/carboplatin




Primary Outcome Measures :
  1. 5-year overall survival rate [ Time Frame: From the completion of the intervention to 5 years. ]
    Five-year survival rate measures survival at 5 years after treatment.


Secondary Outcome Measures :
  1. recurrence rate [ Time Frame: In 1 year after treatment. ]
    Patients who develop SCLC after treatment.

  2. surgery complication [ Time Frame: Through surgery completion, an average of 1 month. ]
    Complications that happen after surgery.

  3. resection rate [ Time Frame: At the end of Perioperative period, an average of 2 weeks. ]
    Patients who are eligible to receive surgery.

  4. tumor biological makers [ Time Frame: At the end of Perioperative period, an average of 2 weeks ]
    A biomarker, or biological marker, generally refers to a measurable indicator of SCLC.

  5. overall survival rate [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 90 months ]
    Patients with SCLC can die directly from that disease or from an unrelated cause (for example, a car accident). When the precise cause of death is not specified called the overall survival rate.

  6. disease-free survival rate [ Time Frame: From date of randomization until the date of first documented progression, whichever came first, assessed up to 40 months ]
    The period after curative treatment [disease eliminated] when no disease can be detected.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • signed informed consent;
  • Ability to comply with research protocols and follow-up procedures;
  • The patient's age is 18 years or older;
  • Histologically or cytologically confirmed as SCLC, chest-enhanced CT, liver and adrenal CT, cranial magnetic resonance, PET-CT/systemic bone imaging, etc. Definitely stage II, IIIA staged patients (according to the UICC 2009 edition staging criteria);
  • Patients must have measurable lesions (according to the RECIST 1.0 standard);
  • Physical status ECOG score is 0~1;
  • Life expectancy is at least 12 weeks;
  • The following laboratory tests were performed within 7 days prior to the first dose to confirm that the patient's bone marrow, liver, and kidney functions met the requirements for participating in the study:

    • Hemoglobin ≥ 9.0 g/dL (can be maintained or exceeded by blood transfusion);
    • The absolute neutrophil count (ANC) ≥ 1.5 × 109;
    • platelet count ≥100×109/mm3;
    • Total bilirubin ≤ 1.5 times the upper limit of normal;
    • Alanine aminotransferase and aspartate aminotransferase ≤2.5 times the normal upper limit;
    • creatinine ≤ 1.5 times the upper limit of normal; and creatinine clearance ≥ 60 ml/min;
    • The international normalized prothrombin time ratio (INR) is less than 1.5 in patients who have not received anticoagulant therapy, and the partial thromboplastin time (APTT) is less than 1.5 times the upper limit of normal. Patients receiving full-dose or parenteral anticoagulant therapy should be stable for at least 2 weeks before entry into clinical studies, and the results of the clotting test can be entered into clinical trials within the limits of local treatment.
    • Women of childbearing age must have a pregnancy test within 7 days of starting treatment and the result is negative.
    • Men and women of appropriate age must have reliable methods of contraception prior to entering the trial and during the study until 30 days after discontinuation. Reliable contraceptive methods will be determined by the principal investigator or designated person.

Exclusion Criteria:

  • Conducted any systemic anti-cancer therapy for SCLC, including cytotoxic drug therapy, targeted drug therapy, and experimental therapy;
  • Surgical treatment for SCLC;
  • Localized radiotherapy for SCLC;
  • Patients with other than SCLC cancer in the five years prior to the start of treatment in this study. Except for cervical carcinoma in situ, cured basal cell carcinoma, bladder epithelial tumor [including Ta and Tis];
  • Any unstable systemic disease (including active infections, uncontrolled high blood pressure, unstable angina, angina pectoris starting in the last 3 months, congestive heart failure (≥New York Heart Association [NYHA] Grade II), myocardial infarction (6 months prior to enrollment), severe arrhythmia requiring medication, liver, kidney, or metabolic disease;
  • Has or is currently suffering from interstitial lung disease;
  • There are no fully controlled eye inflammations or eye infections, or any condition that may lead to the aforementioned eye diseases;
  • Human immunodeficiency virus (HIV) infection is known;
  • Allergies to any of the research drugs;
  • Patients who have undergone major surgery or severe trauma within the first 2 months of the first dose;
  • any malabsorption;
  • pregnant or lactating women;
  • Other investigators think it inappropriate to join the group.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03523234


Contacts
Contact: Peng Zhang, Doctor +86 021 651 15006 zhangpeng1121@outlook.com

Locations
China, Shanghai
Shanghai Pulmonary Hospital Recruiting
Shanghai, Shanghai, China, 200000
Contact: Peng Zhang, doctor         
Sponsors and Collaborators
Peng Zhang

Responsible Party: Peng Zhang, director of science and education department, Shanghai Pulmonary Hospital, Shanghai, China
ClinicalTrials.gov Identifier: NCT03523234     History of Changes
Other Study ID Numbers: k18-066
First Posted: May 14, 2018    Key Record Dates
Last Update Posted: May 14, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Peng Zhang, Shanghai Pulmonary Hospital, Shanghai, China:
neoadjuvant therapy
surgery

Additional relevant MeSH terms:
Lung Neoplasms
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms