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ICON7 - A Randomised, Two-Arm, Multi-Centre Gynaecologic Cancer InterGroup Trial of Adding Bevacizumab to Standard Chemotherapy (Carboplatin and Paclitaxel) in Patients With Epithelial Ovarian Cancer


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

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Trial Information

ICON7 - A Randomised, Two-Arm, Multi-Centre Gynaecologic Cancer InterGroup Trial of Adding Bevacizumab to Standard Chemotherapy (Carboplatin and Paclitaxel) in Patients With Epithelial Ovarian Cancer


OBJECTIVES:

Primary

- Compare the progression-free survival and overall survival of patients with newly
diagnosed ovarian epithelial, fallopian tube, or primary peritoneal cavity cancer
treated with carboplatin and paclitaxel with vs without bevacizumab.

Secondary

- Compare the response rate in patients treated with these regimens.

- Compare the duration of tumor response in patients treated with these regimens.

- Compare the biological progression-free interval, as measured by increasing CA 125
levels, in patients treated with these regimens.

- Compare the safety (e.g., adverse events, laboratory results, and performance status)
of these regimens in these patients.

- Compare the quality of life of patients treated with these regimens.

- Compare the cost-effectiveness of these regimens in these patients.

OUTLINE: This is a multicenter, open-label, randomized, controlled study. Patients are
stratified according to FIGO stage (stage I-III with residual disease ≤ 1 cm vs stage I-III
with residual disease > 1 cm vs stage IV disease), intended time to start chemotherapy after
surgery (≤ 4 weeks vs > 4 weeks), and participating center. Patients are randomized to 1 of
2 treatment arms.

- Arm I (control): Patients receive paclitaxel IV over 3 hours followed by carboplatin IV
over 30-60 minutes on day 1. Treatment repeats every 3 weeks for up to 6 courses in the
absence of disease progression or unacceptable toxicity.

- Arm II: Patients receive bevacizumab IV over 30-90 minutes followed by paclitaxel IV
over 3 hours and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 3
weeks for up to 6 courses in the absence of disease progression or unacceptable
toxicity. Patients then continue to receive bevacizumab alone every 3 weeks for 12
courses.

Quality of life is assessed at baseline, before every course, every 6 weeks for 1 year,
every 3 months until disease progression or for up to 2 years, and then at 3 years. Health
economic data is assessed periodically, including days of inpatient hospitalization visits,
outpatient visits, and use of anticancer therapies.

After completion of study treatment, patients are followed every 3-6 months for 5 years and
then annually thereafter.

Peer Reviewed and Funded or Endorsed by Cancer Research UK.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed ovarian epithelial, fallopian tube, or primary peritoneal
cavity cancer

- Newly diagnosed disease

- Meets 1 of the following staging criteria:

- High-risk stage I or IIA disease (grade 3 disease or clear cell carcinoma only)

- Stage IIB-IV disease (all grades and all histological types)

- Must have undergone initial surgery (e.g., debulking cytoreductive surgery or a
biopsy if the patient has stage IV disease) within the past 6 weeks

- Patients with stage IV disease for which initial surgical debulking was not
appropriate are eligible provided the following criteria are met:

- Stage IV disease diagnosed by histology

- No planned surgery prior to disease progression, including interval
debulking surgery

- Patients with prior early-stage ovarian epithelial or fallopian tube carcinoma
treated with surgery alone are eligible at the time of diagnosis of abdominopelvic
recurrence provided no further interval cytoreductive therapy is planned prior to
disease progression

- Synchronous primary endometrial carcinoma or a past history of primary endometrial
carcinoma allowed provided the following criteria are met:

- Disease ≤ stage IB

- No more than superficial myometrial invasion

- No lymphovascular invasion

- Not poorly differentiated (i.e., no grade 3, papillary serous, or clear cell
disease)

- Measurable or nonmeasurable disease

- No ovarian nonepithelial cancer, including malignant mixed Müllerian tumors

- No borderline tumors (e.g., tumors of low malignant potential)

- No history or clinical suspicion of brain metastases or spinal cord compression

- CT scan or MRI of the brain is mandatory (within 4 weeks prior to randomization)
in case of suspected brain metastases

- Spinal MRI is mandatory (within 4 weeks prior to randomization) in case of
suspected spinal cord compression

PATIENT CHARACTERISTICS:

- ECOG performance status 0-2

- Life expectancy > 12 weeks

- ANC ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Hemoglobin ≥ 9 g/dL (can be post-transfusion)

- INR ≤ 1.5

- APTT ≤ 1.5 times upper limit of normal (ULN)

- Bilirubin ≤ 1.5 times ULN

- ALT and AST ≤ 2.5 times ULN

- Creatinine ≤ 2.0 mg/dL

- Proteinuria ≤ 1+ by urine dipstick OR ≤ 1 g by 24-hour urine collection

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for ≥ 6 weeks after
completion of study therapy

- No significant traumatic injury within the past 4 weeks

- No cerebrovascular accident, transient ischemic attack, or subarachnoid hemorrhage
within the past 6 months

- No other malignancies within the past 5 years except for adequately treated carcinoma
in situ of the cervix, and/or basal cell skin cancer, and/or early endometrial
carcinoma

- No pre-existing sensory or motor neuropathy ≥ grade 2

- No history or evidence of CNS disease (e.g., uncontrolled seizures) by neurological
examination unless adequately treated with standard medical therapy

- No history or evidence of thrombotic or hemorrhagic disorders

- No uncontrolled hypertension (i.e., blood pressure > 150/100 mm Hg despite
antihypertensive therapy)

- No known hypersensitivity to bevacizumab and its excipients, chemotherapy, or
Cremophor EL

- No nonhealing wound, ulcer, or bone fracture

- Patients with granulating incisions healing by secondary intention with no
evidence of facial dehiscence or infection are eligible but require three weekly
wound examinations

- No clinically significant cardiovascular disease, including any of the following:

- Myocardial infarction or unstable angina within the past 6 months

- New York Heart Association class II-IV congestive heart failure

- Poorly controlled cardiac arrhythmia despite medication

- Rate-controlled atrial fibrillation allowed

- Peripheral vascular disease ≥ grade 3 (i.e., symptomatic and interfering with
activities of daily living requiring repair or revision)

- No evidence of other disease or condition, metabolic dysfunction, physical
examination findings, or laboratory findings that would contraindicate the use of an
investigational drug or put the patient at high-risk for treatment-related
complications

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- More than 4 weeks since other prior surgery or open biopsy

- No prior systemic therapy for ovarian cancer (e.g., chemotherapy, monoclonal antibody
therapy, tyrosine kinase inhibitor therapy, or hormonal therapy)

- Prior adjuvant chemotherapy allowed for other malignancies (e.g., breast or
colorectal carcinoma) if malignancy was diagnosed over 5 years ago with no evidence
of subsequent recurrence

- No prior mouse CA 125 antibody

- No prior radiotherapy to the abdomen or pelvis

- More than 10 days since prior and no concurrent chronic use of acetylsalicylic acid
(> 325 mg/day)

- Low-dose (< 325 mg/day) acetylsalicylic acid allowed

- More than 10 days since prior and no concurrent full-dose oral or parenteral
anticoagulants or thrombolytic agents for therapeutic purposes

- Use of therapy for line patency allowed provided INR < 1.5

- More than 30 days since prior and no other concurrent investigational agent or
participation in another clinical trial

- No other concurrent systemic antitumor agents

- No concurrent surgery

- No concurrent maintenance chemotherapy or intraperitoneal chemotherapy (including
cytotoxic chemotherapy)

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival

Safety Issue:

No

Principal Investigator

Tim J. Perren, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Leeds Cancer Centre at St. James's University Hospital

Authority:

Unspecified

Study ID:

CDR0000548777

NCT ID:

NCT00483782

Start Date:

April 2006

Completion Date:

Related Keywords:

  • Fallopian Tube Cancer
  • Ovarian Cancer
  • Primary Peritoneal Cavity Cancer
  • stage IV ovarian epithelial cancer
  • Brenner tumor
  • ovarian carcinosarcoma
  • ovarian clear cell cystadenocarcinoma
  • ovarian endometrioid adenocarcinoma
  • ovarian mixed epithelial carcinoma
  • ovarian mucinous cystadenocarcinoma
  • ovarian serous cystadenocarcinoma
  • ovarian undifferentiated adenocarcinoma
  • stage IA ovarian epithelial cancer
  • stage IB ovarian epithelial cancer
  • stage IC ovarian epithelial cancer
  • stage IIA ovarian epithelial cancer
  • stage IIB ovarian epithelial cancer
  • stage IIC ovarian epithelial cancer
  • stage IIIA ovarian epithelial cancer
  • stage IIIB ovarian epithelial cancer
  • stage IIIC ovarian epithelial cancer
  • stage IA fallopian tube cancer
  • stage IB fallopian tube cancer
  • stage IC fallopian tube cancer
  • stage IIA fallopian tube cancer
  • stage IIB fallopian tube cancer
  • stage IIC fallopian tube cancer
  • stage IIIA fallopian tube cancer
  • stage IIIB fallopian tube cancer
  • stage IIIC fallopian tube cancer
  • stage IV fallopian tube cancer
  • stage IA primary peritoneal cavity cancer
  • stage IB primary peritoneal cavity cancer
  • stage IC primary peritoneal cavity cancer
  • stage IIA primary peritoneal cavity cancer
  • stage IIB primary peritoneal cavity cancer
  • stage IIC primary peritoneal cavity cancer
  • stage IIIA primary peritoneal cavity cancer
  • stage IIIB primary peritoneal cavity cancer
  • stage IIIC primary peritoneal cavity cancer
  • stage IV primary peritoneal cavity cancer
  • Ovarian Neoplasms
  • Peritoneal Neoplasms
  • Fallopian Tube Neoplasms
  • Neoplasms, Glandular and Epithelial

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