Surgery and Chemotherapy With or Without Chemotherapy After Surgery in Treating Patients With Ovarian, Fallopian Tube, Uterine, or Peritoneal Cancer

Recurrent Ovarian Carcinoma Clinical Trial

Official title:

Cytoreductive Surgery With Hyperthermic Intraperitoneal Chemotherapy (HIPEC) and Optional Postoperative Normothermic Intraperitoneal (IP) Chemotherapy to Treat Primary or Recurrent Carcinoma of Ovarian, Fallopian Tube, Uterine, or Peritoneal Origin

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01970722
• Other study ID #: 12316
• Secondary ID: NCI-2013-0194812
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: May 19, 2014
• Est. completion date: December 22, 2024

Study information

• Verified date: April 2024
• Source: City of Hope Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase I trial studies the side effects and how well surgery and heated chemotherapy with or without non-heated chemotherapy after surgery works in treating patients with ovarian, fallopian tube, uterine, or peritoneal cancer. Giving a dose of heated chemotherapy into the abdomen during surgery that is done to remove ovarian, fallopian tube, uterine, or peritoneal cancer may help lower the risk of the cancer coming back. Giving unheated chemotherapy drugs directly into the abdomen after surgery may kill more tumor cells.

Description:

PRIMARY OBJECTIVE:

I. To determine whether cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) followed by postoperative normothermic intraperitoneal (IP) chemotherapy is feasible and safe to administer, as measured by toxicities occurring during treatment or follow-up.

SECONDARY OBJECTIVES:

I. To determine quality of life (QoL) and compare the outcomes to a historical control of IP chemotherapy (no HIPEC) for women with ovarian cancer.

II. To determine whether cytoreductive surgery with HIPEC alone is feasible and safe to administer, as measured by toxicities occurring during treatment or follow-up.

III. To estimate progression-free survival (PFS). IV. To collect biospecimens and perform correlative translational studies focused on understanding the mechanisms of action of HIPEC on ovarian cancer.

OUTLINE:

Patients undergo surgery and receive hyperthermic cisplatin intraperitoneally (IP) over 60 minutes.

Beginning at least 3 weeks after surgery, patients may receive carboplatin, paclitaxel, pegylated liposomal doxorubicin hydrochloride, or gemcitabine hydrochloride IP or intravenously (IV) at the discretion of the medical and gynecologic oncologists.

After completion of study treatment, patients are followed up at 3-6, 6-9, 9-12, and 12-15 months; every 3 months for 1 year; and then every 4 months for 1 year.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 40
• Est. completion date: December 22, 2024
• Est. primary completion date: December 22, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Provided informed consent

• Patient with primary or recurrent International Federation of Gynecology and Obstetrics (FIGO) stage III or IV, or recurrent ovarian, fallopian tube, peritoneal carcinoma, or uterine cancer, confined to abdominal cavity, including those who have completed neoadjuvant chemotherapy and primary surgery

• Gynecologic Oncology Group (GOG) or Eastern Cooperative Oncology Group (ECOG) performance status =< 1 or Karnofsky scale (KPS) >= 70%

• Patients who are platinum-sensitive or platinum resistant

• Candidate for potentially radical, maximal effort cytoreductive surgery at the discretion and expertise of the treating physician

• For patients with newly diagnosed-ovarian/tubal/peritoneal cancer who have received pre-operative neoadjuvant chemotherapy, evidence of response must be documented by at least one of the following:

• Decline in serum cancer antigen (CA) 125 level

• At least a 30% decrease in the sum of the longest diameter of target lesions on radiographic imaging

• Improvement of ascites volume

• Neoadjuvant chemotherapy must be held for at least 3 weeks prior to surgery

• Resolution of any effects of prior therapy (except alopecia and peripheral neuropathy) to the current National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (NCI CTCAE) grade =< 1 and to baseline laboratory values as defined

• Hemoglobin (HGB) >= 9 g/dL

• White blood cell (WBC) >= 3,000/mcL

• Absolute neutrophil count (ANC) >= 1,500/mcL

• Platelets (PLT) >= 100,000/mcL

• Total bilirubin within normal institutional limits

• Serum glutamic oxaloacetic transaminase (SGOT)/serum glutamate pyruvate transaminase (SGPT) < 2.5 x institutional upper limit of normal (ULN)

• Creatinine < 1.5 x ULN or creatinine clearance > 60 ml/min according to Cockcroft-Gault formula

• Neuropathy (sensory and motor) NCI CTCAE grade =< 2

• Prothrombin time (PT) such that international normalized ratio (INR) is < 1.5 (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin or low molecular weight heparin) and a partial thromboplastin time (PTT) < 1.2 times control

• Serum albumin >= 2.5

• No active infection requiring antibiotics

• Preoperative or intraoperative (frozen section) diagnosis of ovarian, peritoneal, fallopian tubal or uterine cancer

• Surgery achieves either no gross residual disease (R0) or optimal cytoreductive status defined as no single lesion measuring more than 5.0 mm in its greatest diameter

• Stable from a cardiopulmonary standpoint to continue with prolonged surgery and anesthesia

Exclusion Criteria:

• Patients with active extra-abdominal disease including active malignant pleural effusion; patients who have been successfully treated with neoadjuvant chemotherapy and no longer have (malignant) pleural effusions may be included

• Patients whose disease has progressed following at least 3 cycles of neoadjuvant chemotherapy as defined by at least one of the following:

• Doubling of serum CA-125 level

• At least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions

• Clinical deterioration (worsening ascites, carcinomatous ileus, malignant bowel obstruction, severe hypoalbuminemia, declining performance status)

• Cardiac or pulmonary conditions that preclude aggressive cytoreductive surgery

• Patients whose circumstances do not permit completion of the study or the required follow-up

• Pregnant, nursing, or of childbearing potential and refuse hysterectomy or bilateral salpingo-oophorectomy

• Other active invasive malignancies, with the exception of non-melanoma skin cancer and breast cancer (if without evidence of disease 1 year after completion of treatment)

• Metastatic non-gynecologic or breast primaries

• Sub-optimal resection as their surgical outcome

• Intraoperative frozen section suggesting hepatobiliary, pancreatic, adrenal, or urinary tract cancer

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Ovarian Epithelial
• Fallopian Tube Neoplasms
• FIGO Stage IVA Ovarian Cancer
• FIGO Stage IVB Ovarian Cancer
• Ovarian Neoplasms
• Peritoneal Neoplasms
• Platinum-Resistant Ovarian Carcinoma
• Recurrence
• Recurrent Fallopian Tube Carcinoma
• Recurrent Ovarian Carcinoma
• Recurrent Primary Peritoneal Carcinoma
• Recurrent Uterine Corpus Carcinoma
• Stage III Fallopian Tube Cancer AJCC v7
• Stage III Ovarian Cancer AJCC v6 and v7
• Stage III Primary Peritoneal Cancer AJCC v7
• Stage III Uterine Corpus Cancer AJCC v7
• Stage IIIA Fallopian Tube Cancer AJCC v7
• Stage IIIA Ovarian Cancer AJCC v6 and v7
• Stage IIIA Primary Peritoneal Cancer AJCC v7
• Stage IIIA Uterine Corpus Cancer AJCC v7
• Stage IIIB Fallopian Tube Cancer AJCC v7
• Stage IIIB Ovarian Cancer AJCC v6 and v7
• Stage IIIB Primary Peritoneal Cancer AJCC v7
• Stage IIIB Uterine Corpus Cancer AJCC v7
• Stage IIIC Fallopian Tube Cancer AJCC v7
• Stage IIIC Ovarian Cancer AJCC v6 and v7
• Stage IIIC Primary Peritoneal Cancer AJCC v7
• Stage IIIC Uterine Corpus Cancer AJCC v7
• Stage IV Fallopian Tube Cancer AJCC v6 and v7
• Stage IV Ovarian Cancer AJCC v6 and v7
• Stage IV Primary Peritoneal Cancer AJCC v7
• Stage IV Uterine Corpus Cancer AJCC v7
• Stage IVA Uterine Corpus Cancer AJCC v7
• Stage IVB Uterine Corpus Cancer AJCC v7

Intervention

Drug:
• Carboplatin
Given IP or IV
• Cisplatin
Given IP
• Gemcitabine Hydrochloride
Given IP or IV

Other:
• Laboratory Biomarker Analysis
Correlative studies

Drug:
• Paclitaxel
Given IP or IV
• Pegylated Liposomal Doxorubicin Hydrochloride
Given IP or IV

Other:
• Quality-of-Life Assessment
Ancillary studies

Procedure:
• Therapeutic Conventional Surgery
Undergo surgery

Locations

Country	Name	City	State
United States	City of Hope Corona	Corona	California
United States	City of Hope Medical Center	Duarte	California
United States	Parkview Hospital Randallia	Fort Wayne	Indiana
United States	City of Hope Upland	Upland	California

Sponsors (2)

Lead Sponsor	Collaborator
City of Hope Medical Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of treatment-related toxicities according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) guidelines	Toxicity for both primary and recurrent groups will be summarized using frequency tables.	Up to 3 months post-surgery
Secondary	Quality of life (QoL) assessed by the Functional Assessment of Cancer Therapy-Ovarian (FACT-O) QoL questionnaire	The FACT-O has four subscales: physical, social/family, emotional, and functional well-being. Answers are on a scale of 0 'not at all' to 4 'very much'. To estimate effect sizes over time, generalized linear models will be used to estimate the correlations between potential prognostic factors. Generalized estimating equations (GEEs) have utility in modeling longitudinal effects across time in prospective cohorts, and the models will include time-dependent covariate structures for continuous outcomes. QoL will be compared to a historical control of intraperitoneal (IP) chemotherapy for women with ovarian cancer.	Up to 15 months post-surgery
Secondary	Progression-free survival (PFS)	PFS will be estimated in both groups. The survival curve will be estimated using Kaplan-Meier method and graphically displayed along with the corresponding 95% confidence curves. The Cox proportional hazards model will be used to derive an estimate of the hazard ratio and its corresponding 95% confidence limits.	From time-of-study entry to time-of-detection of new lesions on computed tomography imaging that is triggered by CA125 progression as defined by Gynecologic Cancer Intergroup Criteria (GCIG) or clinical symptoms or deterioration, assessed up to 3 years