Comparing Impact of Treatment Before or After Surgery in Patients With Stage II-IIIB Resectable Non-small Cell Lung Cancer

Официальное название

Perioperative Versus Adjuvant Systemic Therapy in Patients With Resectable Non-Small Cell Lung Cancer - PROSPECT LUNG

Обзор

This phase III trial compares standard therapy given after surgery (adjuvant) to standard therapy given before and after surgery (perioperative) in treating patients with stage II-IIIB non-small cell lung cancer (NSCLC) that can be removed by surgery (resectable). The usual approach for patients with resectable NSCLC is chemotherapy and/or immunotherapy before surgery, after surgery, or both before and after surgery. This study is being done to find out which approach is better at treating patients with lung cancer. Treatment will be administered according to the current standard of care at the time of enrollment. Chemotherapy options may include cisplatin, carboplatin, pemetrexed, gemcitabine, docetaxel, and vinorelbine at standard doses according to the treating physician. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of tumor cells. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Pemetrexed is in a class of medications called antifolate antineoplastic agents. It works by stopping cells from using folic acid to make deoxyribonucleic acid (DNA) and may kill tumor cells. Gemcitabine is a chemotherapy drug that blocks the cells from making DNA and may kill tumor cells. Docetaxel is in a class of medications called taxanes. It stops tumor cells from growing and dividing and may kill them. Other chemotherapy drugs, such as vinorelbine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading . Immunotherapy with monoclonal antibodies, such as nivolumab, pembrolizumab, and atezolizumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Starting treatment with chemotherapy and immunotherapy prior to surgery and continuing treatment after surgery may be a more effective treatment option than adjuvant therapy alone in patients with stage II-IIIB resectable NSCLC.

Подробное описание

The primary and secondary objectives of the study:

PRIMARY OBJECTIVE:

I. To compare the 3-year real-world event-free survival (rwEFS) rate and overall survival (OS) between perioperative and adjuvant immunotherapy-based treatment for patients with resectable non-small cell lung cancer (dual endpoints).

SECONDARY OBJECTIVES:

I. To compare the rates of surgical resection between the two arms. II. To compare the rates of complete resection (R0) between the two arms. III. To summarize and compare rates of adverse events (AEs) resulting in permanent treatment discontinuation, hospitalization, or death between the two arms.

IV. To evaluate the association between locally defined pathological complete response (pCR) and rwEFS in patients randomized to the perioperative arm (arm 2).

V. To compare the rwEFS post 3-years from randomization between the two arms among patients who do not experience an event by 3 years.

EXPLORATORY OBJECTIVES:

I. To compare outcomes according to the systemic therapy administered on each arm.

II. To compare the sites of relapse between the two treatment arms.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM 1:

SURGERY: Patients undergo surgery within 28 days of registration.

ADJUVANT THERAPY: Patients receive platinum-based doublet chemotherapy (cisplatin, carboplatin, pemetrexed, gemcitabine, docetaxel, and/or vinorelbine) for up to 4 cycles and immune checkpoint inhibitor therapy (nivolumab, pembrolizumab, and/or atezolizumab) for up to 1 year in the absence of disease progression or unacceptable toxicity according to current approved guidelines.

ARM 2:

NEOADJUVANT THERAPY: Within 28 days of registration, patients receive platinum-based doublet chemotherapy (cisplatin, carboplatin, pemetrexed, gemcitabine, docetaxel, and/or vinorelbine) for up to 4 cycles in combination with immune checkpoint inhibitor (nivolumab, pembrolizumab, and/or atezolizumab) according to current approved guidelines.

SURGERY: Patients undergo surgery.

ADJUVANT THERAPY: Patients receive immune checkpoint inhibitor therapy (nivolumab, pembrolizumab, and/or atezolizumab) for up to 1 year in the absence of disease progression or unacceptable toxicity according to current approved guidelines.

Patients also undergo computed tomography (CT) throughout the study and may undergo magnetic resonance imaging (MRI) and/or positron emission tomography (PET)/CT at screening.

After completion of study treatment, patients are followed up every 6 months for up to 10 years.

Вмешательства

• Процедура Surgical Procedure
  undergo surgery
• Препарат Cisplatin
  Give cisplatin
• Препарат Carboplatin
  Give Carboplatin
• Препарат Pemetrexed
  Give Pemetrexed
• Препарат Gemcitabine
  Give Gemcitabine
• Препарат Docetaxel
  Give Docetaxel
• Препарат Vinorelbine
  Give Vinorelbine
• Препарат Nivolumab
  Give Nivolumab
• Препарат Pembrolizumab
  Give Pembrolizumab
• Препарат Atezolizumab
  Give Atezolizumab

Первичные конечные точки

• 3-year real-world event-free survival (rwEFS) [Срок оценки: From the date of randomization to the date of the first of the following events: failure to undergo resection for any reason, recurrence or progression at any time after surgery, or death from any cause, assessed at 3 years]
• Overall survival (OS) [Срок оценки: From randomization until death from any cause, assessed up to 10 years]

Вторичные конечные точки (4)

• Rates of surgical resection [Срок оценки: Up to 10 years.]
• Rates of complete resection (R0) [Срок оценки: Up to 10 years.]
• Incidence of adverse events (AEs) [Срок оценки: Up to 10 years.]
• Pathological complete response (pCR) [Срок оценки: Up to 10 years]

Критерии участия

Критерии включения

• Histologically or cytologically confirmed surgically resectable stage IIA to IIIB NSCLC according to the American Joint Committee on Cancer (AJCC) 9th edition (stage IIA to IIIB NSCLC up to single station N2, according to the AJCC 8th edition)

\* Note: Patients with resectable stage N2a or T4 are eligible, but patients with stage N2b or N3 are not eligible. Patients with known EGFR or ALK alterations are excluded

• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (or Karnofsky ≥ 60%)
• No prior systemic treatment for NSCLC within 5 years except stage 1 and 2 cancers treated with curative intent
• No treatment for another malignancy within 3 years prior to registration, except for stage 1 or 2 cancers treated for curative intent; patients must be disease free for one year prior to registration. Patients with non-melanoma skin cancer, urothelial carcinoma in situ (Tis), noninvasive papillary carcinoma of the urinary bladder (Ta), prostatic intraepithelial neoplasia (PIN), ductal carcinoma in situ (DCIS) of the breast, or cervical intraepithelial neoplasia (CIN) of the uterine cervix are also eligible
• No active autoimmune disease, interstitial lung disease, or transplant that precludes safe treatment with immune checkpoint inhibitors
• HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 415 центров

• University of Alabama at Birmingham Cancer Center — Birmingham
• Fairbanks Memorial Hospital — Fairbanks
• Cancer Center at Saint Joseph's — Phoenix
• Mayo Clinic Hospital in Arizona — Phoenix
• Mercy Hospital Fort Smith — Fort Smith
• NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro — Jonesboro
• CARTI Cancer Center — Little Rock
• Kaiser Permanente-Deer Valley Medical Center — Antioch
• … и ещё 407 центров

Публикации

• Booth A, Hillman S, Laumann K, Zhao YQ, LeBlanc M, Chansky K, Giri S, Dill J, Johnson J, Kelley K, Martin L, Osarogiagbon RU, Morris MJ, Chiang AC, Kozono DE, Blanke CD, Galanis E, Gray JE, Stinchcombe TE, Aljumaily R, Morgensztern D, Mandrekar SJ. PROSPECT-LUNG: A National Clinical Trials Network Trial Advancing Pragmatic Innovation in Cancer Clinical Trials. J Thorac Oncol. 2026 Jul;21(7):103650 PMID 41747891

Идентификаторы

NCT: NCT06632327 · CTIU2317-A082304-S2402 · NCI-2024-06356

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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