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

Phase 1

Active, not recruiting

• Conditions: FIGO Stage IVB Ovarian Cancer; Platinum-Resistant Ovarian Carcinoma; Recurrent Fallopian Tube Carcinoma; FIGO Stage IVA Ovarian Cancer; 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
• Interventions: Drug: Carboplatin; Drug: Cisplatin; Drug: Gemcitabine Hydrochloride; Other: Laboratory Biomarker Analysis; Drug: Paclitaxel; Drug: Pegylated Liposomal Doxorubicin Hydrochloride; Other: Quality-of-Life Assessment; Procedure: Therapeutic Conventional Surgery

• Registration Number: NCT01970722
• Lead Sponsor: City of Hope Medical Center

Brief 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.

Detailed 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.

Study Timeline

• Study First Submitted: 2013-10-23
• Study First Submitted QC: 2013-10-23
• Study First Posted: 2013-10-28
• Study Start: 2014-05-19
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-01
• Last Update Posted: 2025-04-02
• Primary Completion: 2026-02-03
• Study Completion: 2026-02-03

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Female
• Target Recruitment: 40

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (surgery, HIPEC cisplatin)	Carboplatin	Patients undergo surgery and receive hyperthermic cisplatin 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 IV at the discretion of the medical and gynecologic oncologists.
Treatment (surgery, HIPEC cisplatin)	Gemcitabine Hydrochloride	Patients undergo surgery and receive hyperthermic cisplatin 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 IV at the discretion of the medical and gynecologic oncologists.
Treatment (surgery, HIPEC cisplatin)	Laboratory Biomarker Analysis	Patients undergo surgery and receive hyperthermic cisplatin 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 IV at the discretion of the medical and gynecologic oncologists.
Treatment (surgery, HIPEC cisplatin)	Quality-of-Life Assessment	Patients undergo surgery and receive hyperthermic cisplatin 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 IV at the discretion of the medical and gynecologic oncologists.
Treatment (surgery, HIPEC cisplatin)	Therapeutic Conventional Surgery	Patients undergo surgery and receive hyperthermic cisplatin 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 IV at the discretion of the medical and gynecologic oncologists.
Treatment (surgery, HIPEC cisplatin)	Pegylated Liposomal Doxorubicin Hydrochloride	Patients undergo surgery and receive hyperthermic cisplatin 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 IV at the discretion of the medical and gynecologic oncologists.
Treatment (surgery, HIPEC cisplatin)	Cisplatin	Patients undergo surgery and receive hyperthermic cisplatin 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 IV at the discretion of the medical and gynecologic oncologists.
Treatment (surgery, HIPEC cisplatin)	Paclitaxel	Patients undergo surgery and receive hyperthermic cisplatin 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 IV at the discretion of the medical and gynecologic oncologists.

Primary Outcome Measures

Name	Time	Method
Incidence of treatment-related toxicities according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) guidelines	Up to 3 months post-surgery	Toxicity for both primary and recurrent groups will be summarized using frequency tables.

Secondary Outcome Measures

Name	Time	Method
Quality of life (QoL) assessed by the Functional Assessment of Cancer Therapy-Ovarian (FACT-O) QoL questionnaire	Up to 15 months post-surgery	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.
Progression-free survival (PFS)	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	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.

Trial Locations

Locations (4)

City of Hope Medical Center; 🇺🇸 Duarte, California, United States

Parkview Hospital Randallia; 🇺🇸 Fort Wayne, Indiana, United States

City of Hope Corona; 🇺🇸 Corona, California, United States

City of Hope Upland; 🇺🇸 Upland, California, United States