Clinical trial NCT01091636: Intraoperative Hyperthermic Intraperitoneal Chemotherapy With Ovarian Cancer
Official title: Randomized Trial of Intraoperative Hyperthermic Intraperitoneal Chemotherapy Followed by Intravenous Chemotherapy in Patients With Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Epithelial Ovarian Cancer
Lead sponsor: National Cancer Center, Korea
Sponsor class: OTHER_GOV
Collaborators: name: Ajou University
First posted: 2010-03-24
Enrollment: 184
Sex: FEMALE
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: HIPEC vs. no HIPEC after primary cytoreductive surgery or interval cytoreductive surgery
Primary purpose: TREATMENT

Brief summary: The current standard treatment for ovarian cancer, tubal cancer, and primary peritoneal cancer is maximal cytoreductive surgery followed by chemotherapy. Recent randomized trials of Gynecologic Oncology Group (GOG) revealed the survival gain in intraperitoneal chemotherapy compared to the intravenous chemotherapy after the optimal cytoreduction in ovarian cancer (GOG#104, GOG#114, GOG#172). Experts attributed such survival gain to the earlier cycles of intraperitoneal chemotherapy when adhesion was minimal from extensive cytoreductive procedures.

Hyperthermia has an anti-cancer activity itself. Especially, hyperthermia promotes chemotherapy to penetrate deeper into the cancer tissue. Therefore, the combination of intraperitoneal chemotherapy with hyperthermia theoretically could lead to higher response rate and better survival outcomes.

\*HIPEC: hyperthermic intraperitoneal chemotherapy

There will be an interim analysis when 50% of patients are enrolled.

At the interim analysis, a statistical test will be performed. The nominal significance levels will be determined later. The exact nominal significance level will be determined based on the exact number of events at the time of the interim analysis. The Stopping boundaries will be calculated using an O'Brien-Fleming error spending function

Detailed description: If a patient is allocated to operation to remove ovarian cancer and metastatic disease in the abdomen, this trial could be considered. Before operation, laboratory test results, image result, patient's medical history, and baseline quality of life will be checked and reviewed.

When optimal cytoreduction (residual tumor\<1cm) is attained, this HIPEC (hyperthermic intraperitoneal chemotherapy) could be considered. For the primary advanced epithelial ovarian cancer, HIPEC will be performed at random. For the recurrent ovarian cancer, HIPEC will be performed after completion of cytoreductive procedures. Usually, HIPEC takes one and half hours after cytoreductive surgery.

After cytoreductive surgery followed by HIPEC, adjuvant chemotherapy will be added. The cycle of chemotherapy will be determined according to the patients' clinical outcomes. The laboratory test results, image result, patient's medical history, and baseline quality of life will be checked after the operation, during chemotherapy, and after chemotherapy.

Cytoreduction: an operation to remove ovarian cancer and its metastatic disease

There will be an interim analysis when 50% of patients are enrolled.

At the interim analysis, a statistical test will be performed. The nominal significance levels will be determined later. The exact nominal significance level will be determined based on the exact number of events at the time of the interim analysis. The Stopping boundaries will be calculated using an O'Brien-Fleming error spending function

Eligibility criteria: Inclusion Criteria:

1. Disease status Primary ovarian cancer, tubal cancer, and primary peritoneal cancer (Stage III or more)
2. Residual tumor \< 1cm after completion of cytoreductive surgery
3. Age \< 75 year
4. Expected survival \> 3 months
5. Performance status: ECOG 0-1
6. Adequate bone marrow function Hb ≥8 g/dl (After correction in case of iron deficient anemia) WBC ≥ 3,000/mm3, Platelet ≥ 100,000/mm3
7. Adequate renal function Creatinine ≤ 1.5 mg/dl
8. Adequate hepatic function Bilirubin ≤ 1.5 mg/dl and AST and ALT ≤ 80 IU/L
9. Optimal cardiopulmonary function for surgery
10. Voluntary participation after getting written informed consent.

Exclusion Criteria:

1. Unresectable extraperitoneal metastasis (brain, bone, lung parenchyme, and supraclavicular lymph node)
2. Suboptimal debulking (residual tumor \> 1cm)
3. Previous History of other malignancies (except excision of skin cancer, thyroid cancer)
4. Serious heart disease or renal failure
5. Serious cardiopulmonary insufficiency
6. Uncontrolled infection
7. Uncontrolled intercurrent disease
8. Psychogenic disorder
9. Patients who are suitable candidates by legally
10. Pregnant or breast-feeding patients
11. Patients who are unsuitable candidates by doctor's decision
12. MMMT
13. Cancer tissue is not confirmed during surgery after neo-adjuvant chemotherapy

Primary outcomes:
measure: Progression free survival
timeFrame: 2 years
Secondary outcomes:
measure: Overall survival, quality of life
timeFrame: 3 years
Other outcomes:
Locations:
city: Goyang
country: Korea, Republic of
facility: National Cancer Center
state: Gyeonggi
Study officials:
affiliation: National Cancer Center in Korea
name: Sang-Yoon Park, MD, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lim MC, Kang S, Choi J, Song YJ, Park S, Seo SS, Park SY. Hyperthermic intraperitoneal chemotherapy after extensive cytoreductive surgery in patients with primary advanced epithelial ovarian cancer: interim analysis of a phase II study. Ann Surg Oncol. 2009 Apr;16(4):993-1000. doi: 10.1245/s10434-008-0299-y. Epub 2009 Jan 24.
citation: Kim JH, Lee DE, Lee Y, Ha HI, Chang YJ, Chang SJ, Park SY, Lim MC. Quality of life outcomes from the randomized trial of hyperthermic intraperitoneal chemotherapy following cytoreductive surgery for primary ovarian cancer (KOV-HIPEC-01). J Gynecol Oncol. 2022 Jul;33(4):e54. doi: 10.3802/jgo.2022.33.e54. Epub 2022 May 31.
citation: Lim MC, Chang SJ, Park B, Yoo HJ, Yoo CW, Nam BH, Park SY; HIPEC for Ovarian Cancer Collaborators. Survival After Hyperthermic Intraperitoneal Chemotherapy and Primary or Interval Cytoreductive Surgery in Ovarian Cancer: A Randomized Clinical Trial. JAMA Surg. 2022 May 1;157(5):374-383. doi: 10.1001/jamasurg.2022.0143.