Clinical trial NCT04575935: Minimally Invasive Surgery After Neoadjuvant Chemotherapy for the Treatment of Stage IIIC-IV Ovarian, Primary Peritoneal, or Fallopian Tube Cancer, LANCE Trial
Official title: Laparoscopic Cytoreduction After Neoadjuvant Chemotherapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Advanced Ovarian Carcinoma
Fallopian Tube Clear Cell Adenocarcinoma
Fallopian Tube Endometrioid Tumor
Fallopian Tube Serous Neoplasm
Fallopian Tube Transitional Cell Carcinoma
Ovarian Clear Cell Adenocarcinoma
Ovarian Endometrioid Adenocarcinoma
Ovarian Serous Adenocarcinoma
Ovarian Transitional Cell Carcinoma
Primary Peritoneal Clear Cell Adenocarcinoma
Primary Peritoneal Endometrioid Adenocarcinoma
Primary Peritoneal Serous Adenocarcinoma
Primary Peritoneal Transitional Cell Carcinoma
Stage IIIC Fallopian Tube Cancer AJCC v8
Stage IIIC Ovarian Cancer AJCC v8
Stage IIIC Primary Peritoneal Cancer AJCC v8
Stage IV Fallopian Tube Cancer AJCC v8
Stage IV Ovarian Cancer AJCC v8
Stage IV Primary Peritoneal Cancer AJCC v8
Stage IVA Fallopian Tube Cancer AJCC v8
Stage IVA Ovarian Cancer AJCC v8
Stage IVA Primary Peritoneal Cancer AJCC v8
Stage IVB Fallopian Tube Cancer AJCC v8
Stage IVB Ovarian Cancer AJCC v8
Stage IVB Primary Peritoneal Cancer AJCC v8
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2020-10-05
Enrollment: 580
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Disease free survival (DFS)
timeFrame: Between randomization and physical or radiographic evidence of recurrence (local/distant) or death (all causes), assessed up to 5 years
Secondary outcomes:
measure: Health related-quality of life (HR-QoL)
timeFrame: Up to 1 year post surgery chemotherapy
measure: Health related-quality of life (HR-QoL)
timeFrame: Up to 1 year post surgery chemotherapy
measure: Health related-quality of life (HR-QoL)
timeFrame: Up to 1 year post surgery chemotherapy
measure: Health related-quality of life (HR-QoL)
timeFrame: Up to 1 year post surgery chemotherapy
measure: Optimal cytoreduction
timeFrame: At the end of surgery
measure: Complete cytoreduction
timeFrame: At the end of surgery
measure: Overall survival (OS)
timeFrame: Between randomization and death (all causes), assessed up to 5 years
measure: Surgical morbidity
timeFrame: Up to 6 months post surgery
measure: Mortality
timeFrame: Up to 6 months post surgery
measure: Intraoperative injuries
timeFrame: During surgery
measure: Minimally invasive surgery (MIS) converted to laparotomy
timeFrame: During surgery
measure: Cost of the procedure
timeFrame: Up to 6 months post surgery
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami Miller School of Medicine-Sylvester Cancer Center
state: Florida
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: New York
country: United States
facility: NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
state: New York
city: Durham
country: United States
facility: Duke
state: North Carolina
city: Houston
country: United States
facility: Lyndon Baines Johnson General
state: Texas
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
city: Madison
country: United States
facility: University of Wisconsin Carbone Cancer Center
state: Wisconsin
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Jose A Rauh-Hain
role: PRINCIPAL_INVESTIGATOR
References: