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Randomized Phase II Study of Intraperitoneal Versus Intravenous Chemotherapy Following Neoadjuvant Chemotherapy in Ovarian Cancer

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00993655
First Posted: October 12, 2009
Last Update Posted: August 10, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
National Cancer Institute (NCI)
Grupo Español de Investigación en Cáncer de Ovario
Cancer Research UK
Southwest Oncology Group
Information provided by (Responsible Party):
Canadian Cancer Trials Group
  Purpose

RATIONALE: Drugs used in chemotherapy, such as paclitaxel, carboplatin, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) and giving them in different ways may kill more tumor cells. It is not yet known which combination chemotherapy regimen is more effective in treating patients with ovarian epithelial cancer, primary peritoneal cancer, and fallopian tube cancer.

PURPOSE: This randomized phase II trial is comparing the side effects of three combination chemotherapy regimens and to see how well they work in treating patients with stage IIB, stage IIC, stage III, or stage IV ovarian epithelial cancer, primary peritoneal cancer, or fallopian tube cancer.


Condition Intervention Phase
Fallopian Tube Cancer Metastatic Cancer Ovarian Cancer Peritoneal Cavity Cancer Drug: carboplatin Drug: cisplatin Drug: paclitaxel Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Intraperitoneal (IP) Plus Intravenous (IV) Chemotherapy Versus IV Carboplatin Plus Paclitaxel in Patients With Epithelial Ovarian Cancer Optimally Debulked at Surgery Following Neoadjuvant Intravenous Chemotherapy

Resource links provided by NLM:


Further study details as provided by Canadian Cancer Trials Group:

Primary Outcome Measures:
  • 9-month Progression Rate Post-randomization [ Time Frame: 9 months ]
    It is defined as proportion of patients who had progressed at or before 9 months after randomization, i.e., the time from the randomization to the date when the first observation of disease progression (earliest of the date when the first CA 125 meets progression definition and the date of first objective relapse or progression, defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions, recorded) has been documented or when death due to any cause has been observed was less than or equal to 9 months.


Secondary Outcome Measures:
  • Progression Free Survival [ Time Frame: During the study with median follow-up of 33 months ]
    Time from the day of randomization until the time when first observation of disease progression (earliest of the dates of first CA125 which meets progression definition and first objective relapse or progression defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions, has been documented or when death due to any cause has been observed.

  • Overall Survival [ Time Frame: During the study with median follow-up of 33 months ]
    Time from the day of randomization to death from any cause.


Enrollment: 275
Study Start Date: September 2009
Study Completion Date: July 2016
Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: IV carboplatin + IV paclitaxel
ARM 1: Paclitaxel 135 mg/m2 intravenous day 1 plus Carboplatin AUC 5 if measured GFR or AUC6 if estimated GFR intravenous day 1; Paclitaxel 60 mg/m2 intravenous day 8. Cycles given Q 21 days x 3 cycles
Drug: carboplatin
Carboplatin AUC 5 if measured GFR or AUC6 if calculated GFR intravenous or intraperitoneal.
Drug: paclitaxel
Paclitaxel 135 mg/m2 intravenous day 1 plus Paclitaxel 60 mg/m2 intraperitoneal or intravenously day 8. Cycles given Q 21 days x 3 cycles
Active Comparator: IP cisplatin + IV/IP paclitaxel
ARM 2: Paclitaxel 135 mg/m2 intravenous day 1 plus Cisplatin 75 mg/m2 intraperitoneal day 1; Paclitaxel 60 mg/m2 intraperitoneal day 8. Cycles given Q 21 days x 3 cycles (Phase II cisplatin arm closed to accrual on 2014-FEB-03)
Drug: cisplatin
Cisplatin 75 mg/m2 intraperitoneal day 1
Drug: paclitaxel
Paclitaxel 135 mg/m2 intravenous day 1 plus Paclitaxel 60 mg/m2 intraperitoneal or intravenously day 8. Cycles given Q 21 days x 3 cycles
Active Comparator: IP carboplatin + IV/IP paclitaxel
ARM 3: Paclitaxel 135 mg/m2 intravenous day 1 plus Carboplatin AUC 5 if measured GFR or AUC6 if estimated GFR intraperitoneal day 1; Paclitaxel 60 mg/m2 intraperitoneal day 8. Cycles given Q 21 days x 3 cycles
Drug: carboplatin
Carboplatin AUC 5 if measured GFR or AUC6 if calculated GFR intravenous or intraperitoneal.
Drug: paclitaxel
Paclitaxel 135 mg/m2 intravenous day 1 plus Paclitaxel 60 mg/m2 intraperitoneal or intravenously day 8. Cycles given Q 21 days x 3 cycles

Detailed Description:

OBJECTIVES:

Primary

  • To compare the efficacy of the selected IP chemotherapy regimen (Arm 3: IV paclitaxel and IP carboplatin plus day 8 IP paclitaxel) versus IV carboplatin plus paclitaxel (Arm 1) in patients with epithelial ovarian cancer optimally debulked at surgery following neoadjuvant intravenous chemotherapy. Nine month progressive rate post randomization is the primary endpoint for assessment of efficacy.

Secondary

  • To compare IP plus IV chemotherapy versus IV carboplatin plus paclitaxel with respect to progression free survival and overall survival.

OUTLINE: This is a multicenter study. Patients are stratified according to cooperative group, residual disease (observable [e.g., macroscopic] disease that is evident at end of delayed primary debulking surgery vs no evidence of observable disease at end of delayed primary debulking surgery), reason for delayed primary debulking surgery at initial diagnosis (nonresectable disease vs other reasons), and timing of intraperitoneal catheter insertion (intra-operative catheter insertion vs post-operative insertion).

  • Phase II: Patients are randomized to 1 of 3 treatment groups.

    • ARM 1: Paclitaxel 135 mg/m2 intravenous day 1 plus Carboplatin AUC 5 if measured GFR or AUC6 if estimated GFR intravenous day 1; Paclitaxel 60 mg/m2 intravenous day 8. Cycles given Q 21 days x 3 cycles
    • ARM 2: Paclitaxel 135 mg/m2 intravenous day 1 plus Cisplatin 75 mg/m2 intraperitoneal day 1; Paclitaxel 60 mg/m2 intraperitoneal day 8. Cycles given Q 21 days x 3 cycles (Phase II cisplatin arm closed to accrual on 2014-Feb-03)
    • ARM 3: Paclitaxel 135 mg/m2 intravenous day 1 plus Carboplatin AUC 5 if measured GFR or AUC6 if estimated GFR intraperitoneal day 1; Paclitaxel 60 mg/m2 intraperitoneal day 8. Cycles given Q 21 days x 3 cycles.

Patients also receive carboplatin IP on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity.

  • Expanded Phase II: Patients are randomized to 1 of 2 treatment groups.

    • Arm I: Patients receive paclitaxel and carboplatin as in phase II, arm I.
    • Arm III: Patients receive paclitaxel and cisplatin as in phase II, arm II or paclitaxel and carboplatin as in phase II, arm III.

Patients complete quality of life questionnaires EORTC QLQ-C30, ovarian cancer module (EORTC QLQ-OV28), and FACT/GOG-Ntx at baseline, on day 1 of courses 2 and 3, at 3, 6 and 12 months after completion of study treatment, and then annually until disease progression, death, or initiation of second-line therapy.

After completion of study treatment, patients are followed at 6 weeks, every 3 months for 2 years, every 6 months for 2 years, and then annually until progression, death, or initiation of second-line therapy.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed ovarian epithelial, primary serous type peritoneal, or fallopian tube carcinoma

    • Patients with ovarian cancer of the clear cell histology are eligible. Histologic confirmation is preferably by biopsy or limited excision prior to neo‐adjuvant treatment. If the diagnosis prior to neo-adjuvant chemotherapy is based on cytology, histologic confirmation is required prior to randomization. Histologic confirmation can be obtained at the time of debulking surgery by intra-operative frozen section, thus permitting intra-operative randomization, or by final pathologic review of the resected specimen if randomization is to be performed following debulking surgery.
    • Initial FIGO stage IIB-III disease

      • Stage IV disease allowed provided the only criterion for stage IV disease is the presence of a pleural effusion confirmed to be associated with positive cytology for ovarian cancer
  • Completed ≥ 3 but no more than 4 courses of platinum-based neoadjuvant chemotherapy prior to the first debulking surgery
  • Meets the following criteria for surgical treatment prior to randomization:

    • Initial Diagnosis: No debulking surgery was attempted or completed.
    • The patient's first cytoreductive (debulking) surgery must be after neoadjuvant chemotherapy (Delayed Primary Debulking). The delayed primary debulking surgery must be completed no more than 4 weeks after commencing administering of the last cycle of neoadjuvant chemotherapy and must be completed no more than 6 weeks prior to randomization.
    • Surgery will include total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy and any additional procedures required to achieve maximal cytoreduction with residual disease of 1 cm or less as assessed by the surgeon at the end of surgery.

      • Delayed primary debulking surgery must be completed no more than 4 weeks after the last course of neoadjuvant chemotherapy and must be completed no more than 6 weeks prior to randomization
    • Surgery will include total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and any additional procedures required to achieve maximal cytoreduction with residual disease of ≤ 1 cm as assessed by the surgeon at the end of surgery
  • No borderline ovarian tumors (i.e., tumors of low malignant potential) alone
  • No mucinous tumor

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Life expectancy ≥ 12 weeks
  • Granulocyte count ≥ 1.5 x 10^9/L
  • Platelet count ≥ 100 x 10^9/L
  • Serum creatinine ≤ upper limit of normal (ULN) OR > ULN to ≤ 1.25 ULN provided measured creatinine clearance is > 60 mL/min
  • Serum bilirubin normal
  • AST/ALT ≤ 2.5 times ULN
  • Fertile patients must use effective contraception
  • Able (i.e., sufficiently fluent) and willing to complete the quality of life questionnaires
  • Accessible for treatment and follow-up
  • No history of other malignancy, except adequately treated nonmelanoma skin cancer, curatively treated carcinoma in situ of the cervix, or other solid tumors curatively treated with no evidence of disease for ≥ 5 years
  • No uncontrolled atrial or ventricular arrhythmias including second or third degree heart block unless managed with implanted pacemaker

    • Patients with a history of first degree heart block are eligible
  • No documented myocardial infarction within the past 6 months preceding randomization (pretreatment ECG evidence only of infarct will not exclude patients)
  • No diagnosis of bowel obstruction
  • No serious illness or medical condition which would not permit the patient to be managed according to protocol including, but not limited to, any of the following:

    • Prior allergic reactions to drugs containing cremophor or to compounds chemically related to cisplatin, paclitaxel, or carboplatin
    • Symptomatic congestive heart failure within the past 6 months or other conditions which would lead to a contraindication of a high-volume saline diuresis
    • History of significant neurologic or psychiatric disorder which would impair the ability to obtain consent
    • Active uncontrolled infection
    • Persistent peripheral neuropathy or hearing loss ≥ grade 2 resulting from prior therapy
    • Extensive intraperitoneal adhesion intra- or post-operatively which would impede intraperitoneal treatment delivery

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior therapy for ovarian cancer, except for neoadjuvant platinum-based chemotherapy and surgery
  • No concurrent intraperitoneal adhesion barriers
  • No other concurrent anticancer treatment, including cytotoxic agents, biological response modifiers, immunotherapy, anticancer hormone therapy, or investigational drug therapy
  • No other concurrent experimental drugs or anticancer therapy
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00993655


  Show 50 Study Locations
Sponsors and Collaborators
Canadian Cancer Trials Group
National Cancer Institute (NCI)
Grupo Español de Investigación en Cáncer de Ovario
Cancer Research UK
Southwest Oncology Group
Investigators
Study Chair: Helen J. Mackay, MD Princess Margaret Hospital, Canada
Study Chair: Diane M. Provencher, MD, FRCS, FACOG Hopital Notre-Dame du CHUM
  More Information

Responsible Party: Canadian Cancer Trials Group
ClinicalTrials.gov Identifier: NCT00993655     History of Changes
Other Study ID Numbers: OV21
CAN-NCIC-OV21 ( Registry Identifier: PDQ (NCI US Physician Data Query) )
UCL08/0379
GEICO-0902 ( Other Identifier: GEICO )
SWOG OV.21 ( Other Identifier: South West Oncology Group )
CDR0000655241 ( Other Identifier: PDQ )
First Submitted: October 9, 2009
First Posted: October 12, 2009
Results First Submitted: June 8, 2017
Results First Posted: August 10, 2017
Last Update Posted: August 10, 2017
Last Verified: July 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Canadian Cancer Trials Group:
peritoneal cavity cancer
fallopian tube cancer
stage II ovarian epithelial cancer
stage III ovarian epithelial cancer
stage IV ovarian epithelial cancer
malignant pleural effusion
ovarian clear cell cystadenocarcinoma
ovarian clear cell tumor with proliferating activity

Additional relevant MeSH terms:
Ovarian Neoplasms
Fallopian Tube Neoplasms
Neoplasm Metastasis
Peritoneal Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Fallopian Tube Diseases
Neoplastic Processes
Pathologic Processes
Abdominal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Paclitaxel
Albumin-Bound Paclitaxel
Cisplatin
Carboplatin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators