Minimally Invasive Surgery After Neoadjuvant Chemotherapy for the Treatment of Stage IIIC-IV Ovarian, Primary Peritoneal, or Fallopian Tube Cancer, LANCE Trial

Официальное название

Laparoscopic Cytoreduction After Neoadjuvant Chemotherapy

Обзор

This phase III trial compares minimally invasive surgery (MIS) to laparotomy in treating patients with stage IIIC-IV ovarian, primary peritoneal, or fallopian tube cancer who are receiving chemotherapy before and after surgery (neoadjuvant chemotherapy). MIS is a surgical procedure that uses small incision(s) and is intended to produce minimal blood loss and pain for the patient. Laparotomy is a surgical procedure which allows the doctors to remove some or all of the tumor and check if the disease has spread to other organs in the body. MIS may work the same or better than standard laparotomy after chemotherapy in prolonging the return of the disease and/or improving quality of life after surgery.

Подробное описание

PRIMARY OBJECTIVE:

I. To examine whether MIS is non-inferior to laparotomy in terms of disease free survival (DFS) in women with advanced stage epithelial ovarian cancer (EOC) that received 3 to 4 cycles of neoadjuvant chemotherapy (NACT).

SECONDARY OBJECTIVES:

I. To determine if there are differences in health-related quality of life (HR-QoL) in patients undergoing MIS versus (vs) laparotomy as assessed with the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30), QLQ-Ovarian Cancer Module (OV28), and Functional Assessment of Cancer Therapy-General (FACT-G7).

II. To determine if there are differences between patients undergoing MIS vs laparotomy in the rate of optimal cytoreduction (defined as residual tumor nodules each measuring 1 cm or less in maximum diameter) and complete cytoreduction (defined as no evidence of macroscopic disease).

III. To examine whether MIS is non-inferior to laparotomy in terms of overall survival (OS) in women with advanced stage EOC that received 3 to 4 cycles of NACT.

IV. To determine if there are differences between patients undergoing MIS vs laparotomy in surgical morbidity and mortality, intraoperative injuries, and post-operative complications.

V. To determine the rates of MIS converted to laparotomy and the reasons.

VI. To determine if there are any difference in costs and cost-effectiveness between patients undergoing MIS vs laparotomy.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients undergo MIS within 6 weeks after last cycle of standard of care neoadjuvant chemotherapy. If during MIS the surgeon thinks complete gross resection can only be accomplished by performing an open procedure, patients may undergo laparotomy instead. Within 6 weeks after surgery, patients receive standard of care chemotherapy.

ARM B: Patients undergo laparotomy within 6 weeks after last cycle of standard of care neoadjuvant chemotherapy. Within 6 weeks after surgery, patients receive standard of care chemotherapy.

After completion of study, patients are followed up within 6 weeks of completing post-surgery chemotherapy, then every 3 months for the first 2 years, and then every 6 months for 3 years.

Вмешательства

• Препарат Chemotherapy
  Receive standard of care chemotherapy
• Процедура Laparotomy
  Undergo laparotomy
• Процедура Minimally Invasive Surgery
  Undergo MIS
• Другое Quality-of-Life Assessment
  Ancillary studies
• Другое Questionnaire Administration
  Ancillary studies

Первичные конечные точки

• Disease free survival (DFS) [Срок оценки: Between randomization and physical or radiographic evidence of recurrence (local/distant) or death (all causes), assessed up to 5 years]

Вторичные конечные точки (12)

• Health related-quality of life (HR-QoL) [Срок оценки: Up to 1 year post surgery chemotherapy]
• Health related-quality of life (HR-QoL) [Срок оценки: Up to 1 year post surgery chemotherapy]
• Health related-quality of life (HR-QoL) [Срок оценки: Up to 1 year post surgery chemotherapy]
• Health related-quality of life (HR-QoL) [Срок оценки: Up to 1 year post surgery chemotherapy]
• Optimal cytoreduction [Срок оценки: At the end of surgery]
• Complete cytoreduction [Срок оценки: At the end of surgery]
• Overall survival (OS) [Срок оценки: Between randomization and death (all causes), assessed up to 5 years]
• Surgical morbidity [Срок оценки: Up to 6 months post surgery]
• Mortality [Срок оценки: Up to 6 months post surgery]
• Intraoperative injuries [Срок оценки: During surgery]
• Minimally invasive surgery (MIS) converted to laparotomy [Срок оценки: During surgery]
• Cost of the procedure [Срок оценки: Up to 6 months post surgery]

Критерии участия

Критерии включения

• Age ≥ 18 years old
• Stage IIIC or IV, high-grade (serous, endometrioid, clear-cell, transitional carcinomas), invasive epithelial ovarian carcinoma, primary peritoneal carcinoma, or fallopian-tube carcinoma or pathology consistent with high-grade mullerian carcinoma.
• Patient is considered by treating physician to be a surgical candidate after completion of 3 to 4 cycles of platinum-based chemotherapy, or an investigational neoadjuvant regimen given according to protocol, with complete radiologic resolution of any disease outside the abdominal cavity. Pleural effusions are acceptable per the local PI's discretion.
• Normalization of CA-125 according to individual participating center reference range (Note: Among patients with a normal CA-125 at initiation of therapy, the CA-125 cannot exceed 35 U/mL at the completion of NACT prior to interval debulking surgery.) or has a CA-125 value ≤500 and is scheduled to undergo a diagnostic laparoscopy prior to debulking surgery. a. For patients undergoing diagnostic laparoscopy, surgeon considers that optimal debulking is feasible either by MIS or laparotomy.
• Timeframe of < 6 weeks (42 days) from the last cycle of NACT to interval debulking surgery. Overall timeframe may be extended per MD Anderson PI discretion.
• ECOG performance status 0-2
• Signed informed consent and ability to comply with follow-up
• Negative pregnancy test by blood or urine (within 14 days prior to surgery)
• Disease free of other active malignancies in the previous five years, except basal and squamous cell carcinomas of the skin

Критерии исключения

• Evidence of tumor not amenable to minimally invasive resection on pre-operative imaging (CT, PET-CT, or MRI) including but not limited to the following findings that may preclude minimally invasive resection per surgeon's assessment. • Failure of improvement of ascites during NACT (trace ascites is allowed) • Small bowel or gastric tumor involvement • Colon or rectal tumor involvement • Diaphragmatic tumor involvement • Splenic or hepatic surface or parenchymal tumor involvement • Mesenteric tumor involvement • Tumor infiltration of the lesser peritoneal sac
• History of psychological, familial, sociological or geographical condition potentially preventing compliance with the study protocol and follow-up schedule
• Inability to tolerate prolonged Trendelenburg position or pneumoperitoneum as deemed by participating institution's clinicians
• Any other contraindication to MIS as assessed by the clinician

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

Простое слепое

Основная цель

Лечение

Центры проведения

США · 13 центров

• University of Miami Miller School of Medicine-Sylvester Cancer Center — Miami
• Cleveland Clinic Foundation - Florida — Weston
• Massachusetts General Hospital — Boston
• Dana Farber Cancer Institute — Boston
• NYU Langone Health — Mineola
• Columbia University Medical Center — New York
• Duke — Durham
• Cleveland Clinic — Cleveland
• … и ещё 5 центров

Канада · 2 центра

• Arthur J.E. Child Comprehensive Cancer Centre - Calgary — Calgary
• University Health Network - Princess Margaret Cancer Centre — Toronto

Италия · 2 центра

• Sant'Orsola Hospital di Bologna — Bologna
• Fondazione Policlinico Universitario Agostino Gemelli IRCCS — Rome

Мексика · 1 центр

• Instituto Nacional de Cancerología (Mexico) — Tlalpan

Нидерланды · 1 центр

• Amsterdam UMC - Locatie AMC | H5Zuid 154 — Amsterdam

Публикации

• Rauh-Hain JA, Melamed A, Pareja R, May T, Sinno A, McNally L, Horowitz NS, De Iaco P, Michener CM, Van Lonkhuijzen L, Iniesta MD, Yuan Y, Ramirez PT, Fagotti A. Laparoscopic Cytoreduction After Neoadjuvant Chemotherapy in High-Grade Epithelial Ovarian Cancer: A LANCE Randomized Clinical Trial. JAMA Netw Open. 2024 Nov 4;7(11):e2446325. doi: 10.1001/jamanetworkopen.2024.46325. PMID 39570589

Идентификаторы

NCT: NCT04575935 · 2020-0165 · NCI-2020-04165 · 2020-0165

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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