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

Primary Purpose

FIGO Stage IVA Ovarian Cancer, FIGO Stage IVB Ovarian Cancer, Platinum-Resistant Ovarian Carcinoma

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Carboplatin
Cisplatin
Gemcitabine Hydrochloride
Laboratory Biomarker Analysis
Paclitaxel
Pegylated Liposomal Doxorubicin Hydrochloride
Quality-of-Life Assessment
Therapeutic Conventional Surgery
Sponsored by
City of Hope Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for FIGO Stage IVA Ovarian Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • City of Hope Corona
  • City of Hope Medical Center
  • City of Hope Upland
  • Parkview Hospital Randallia

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (surgery, HIPEC cisplatin)

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.

Full Information

First Posted
October 23, 2013
Last Updated
March 28, 2023
Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT01970722
Brief Title
Surgery and Chemotherapy With or Without Chemotherapy After Surgery in Treating Patients With Ovarian, Fallopian Tube, Uterine, or Peritoneal Cancer
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
May 19, 2014 (Actual)
Primary Completion Date
December 22, 2023 (Anticipated)
Study Completion Date
December 22, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
FIGO Stage IVA Ovarian Cancer, FIGO Stage IVB Ovarian Cancer, Platinum-Resistant Ovarian Carcinoma, 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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment (surgery, HIPEC cisplatin)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Other Intervention Name(s)
Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo
Intervention Description
Given IP or IV
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Other Intervention Name(s)
Abiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone''s Chloride, Peyrone''s Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, Platosin
Intervention Description
Given IP
Intervention Type
Drug
Intervention Name(s)
Gemcitabine Hydrochloride
Other Intervention Name(s)
dFdCyd, Difluorodeoxycytidine Hydrochloride, FF 10832, FF-10832, FF10832, Gemcitabine HCI, Gemzar, LY-188011, LY188011
Intervention Description
Given IP or IV
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Other Intervention Name(s)
Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat
Intervention Description
Given IP or IV
Intervention Type
Drug
Intervention Name(s)
Pegylated Liposomal Doxorubicin Hydrochloride
Other Intervention Name(s)
ATI-0918, Caelyx, DOX-SL, Doxil, Doxilen, Doxorubicin HCl Liposomal, Doxorubicin HCl Liposome, Doxorubicin Hydrochloride Liposome, Duomeisu, Evacet, LipoDox, Lipodox 50, Liposomal Adriamycin, liposomal doxorubicin hydrochloride, Liposomal-Encapsulated Doxorubicin, Pegylated Doxorubicin HCl Liposome, S-Liposomal Doxorubicin, Stealth Liposomal Doxorubicin, TLC D-99
Intervention Description
Given IP or IV
Intervention Type
Other
Intervention Name(s)
Quality-of-Life Assessment
Other Intervention Name(s)
Quality of Life Assessment
Intervention Description
Ancillary studies
Intervention Type
Procedure
Intervention Name(s)
Therapeutic Conventional Surgery
Intervention Description
Undergo surgery
Primary Outcome Measure Information:
Title
Incidence of treatment-related toxicities according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) guidelines
Description
Toxicity for both primary and recurrent groups will be summarized using frequency tables.
Time Frame
Up to 3 months post-surgery
Secondary Outcome Measure Information:
Title
Quality of life (QoL) assessed by the Functional Assessment of Cancer Therapy-Ovarian (FACT-O) QoL questionnaire
Description
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.
Time Frame
Up to 15 months post-surgery
Title
Progression-free survival (PFS)
Description
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.
Time Frame
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

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thanh Dellinger
Organizational Affiliation
City of Hope Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
City of Hope Corona
City
Corona
State/Province
California
ZIP/Postal Code
92879
Country
United States
Facility Name
City of Hope Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
City of Hope Upland
City
Upland
State/Province
California
ZIP/Postal Code
91786
Country
United States
Facility Name
Parkview Hospital Randallia
City
Fort Wayne
State/Province
Indiana
ZIP/Postal Code
46805
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
35357903
Citation
Dellinger TH, Han ES, Raoof M, Lee B, Wu X, Cho H, He TF, Lee P, Razavi M, Liang WS, Schmolze D, Priceman SJ, Lee S, Lin WC, Lin JF, Kebria M, Hakim A, Ruel N, Stewart DB, Wang EW, Paz BI, Wakabayashi MT, Cristea MC, Rodriguez-Rodriguez L. Hyperthermic Intraperitoneal Chemotherapy-Induced Molecular Changes in Humans Validate Preclinical Data in Ovarian Cancer. JCO Precis Oncol. 2022 Mar;6:e2100239. doi: 10.1200/PO.21.00239. Erratum In: JCO Precis Oncol. 2022 Jun;6:e2200296.
Results Reference
derived

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

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