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A Phase II/III 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


Phase 2/Phase 3
18 Years
N/A
Open (Enrolling)
Female
Fallopian Tube Cancer, Metastatic Cancer, Ovarian Cancer, Peritoneal Cavity Cancer

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Trial Information

A Phase II/III 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


OBJECTIVES:

Primary

- To determine if intraperitoneal platinum-based chemotherapy leads to improved
progression-free and overall survival as compared with intravenous chemotherapy in
patients with stage IIB-III or stage IV (on the basis of pleural effusion only with
positive cytology) ovarian epithelial, serous type peritoneal, or fallopian tube cancer
who have received optimal debulking surgery following neoadjuvant intravenous
chemotherapy.

- To identify which of the two IP regimens will continue into the phase III portion of
the trial. (Phase II)

- To compare the efficacy of the selected IP plus IV chemotherapy regimen versus IV
carboplatin plus paclitaxel in these patients. (Phase III)

Secondary

- To compare IP plus IV chemotherapy versus IV carboplatin plus paclitaxel with respect
to overall survival, toxic effects, quality of life, and economic evaluation.

- To determine components of nursing interventions associated with administering
intraperitoneal therapy and to correlate these interventions with treatment efficacy,
toxic effects, and quality of life.

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 I: Patients receive paclitaxel IV over 3 hours on day 1 and over 1 hour on day
8. Patients also receive carboplatin IV over 30 minutes on day 1. Treatment
repeats every 21 days for 3 courses in the absence of disease progression or
unacceptable toxicity.

- Arm II: Patients receive paclitaxel IV over 3 hours on day 1 and intraperitoneally
(IP) on day 8. Patients also receive cisplatin IP on day 1. Treatment repeats
every 21 days for 3 courses in the absence of disease progression or unacceptable
toxicity.

- Arm III: Patients receive paclitaxel IV over 3 hours on day 1 and IP on day 8.
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.

- Phase III: Patients are randomized to 1 of 2 treatment groups.

- Arm I: Patients receive paclitaxel and carboplatin as in phase II, arm I.

- Arm II: 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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

9-month progression rate post-randomization

Outcome Time Frame:

8 years

Safety Issue:

No

Principal Investigator

Helen J. Mackay, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Princess Margaret Hospital, Canada

Authority:

Canada: Health Canada

Study ID:

OV21

NCT ID:

NCT00993655

Start Date:

September 2009

Completion Date:

January 2021

Related Keywords:

  • Fallopian Tube Cancer
  • Metastatic Cancer
  • Ovarian Cancer
  • Peritoneal Cavity Cancer
  • 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
  • Neoplasm Metastasis
  • Neoplasms
  • Neoplasms, Second Primary
  • Ovarian Neoplasms
  • Peritoneal Neoplasms
  • Fallopian Tube Neoplasms
  • Neoplasms, Glandular and Epithelial

Name

Location

University of Oklahoma Health Sciences CenterOklahoma City, Oklahoma  73104
Women and Infants Hospital of Rhode IslandProvidence, Rhode Island  02905
CoxHealthSpringfield, Missouri  65807
Mercy-SpringfieldSpringfield, Missouri  65804
Univ of Utah (Huntsman Cancer Institute)Salt Lake City, Utah  84132
Northwest CCOP - Multicare Health SystemTacoma, Washington  98415