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An International Phase III Randomised Trial of Dose Fractionated Chemotherapy Compared to Standard Three Weekly Chemotherapy, Following Immediate Primary Surgery or as Part of Delayed Primary Surgery, for Women With Newly Diagnosed Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer


Phase 3
18 Years
N/A
Open (Enrolling)
Female
Ovarian Cancer

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Trial Information

An International Phase III Randomised Trial of Dose Fractionated Chemotherapy Compared to Standard Three Weekly Chemotherapy, Following Immediate Primary Surgery or as Part of Delayed Primary Surgery, for Women With Newly Diagnosed Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer


ICON8 is a three-arm, three stage trial. Patients will be randomised in a 1:1:1 ratio.
Patients in arm 1 (control arm) will receive weekly carboplatin and paclitaxel on day 1 of a
21-day cycle for 6 cycles. Patients in arm 2 will receive carboplatin on day 1 and
dose-fractionated weekly paclitaxel on day 1, 8 and 15 of a 21-day cycle for 6 cycles.
Patients in arm 3 will receive dose-fractionated weekly carboplatin and dose-fractionated
weekly paclitaxel on day 1, 8 and 15 of a 21-day cycle for 6 cycles.

The trial will have three planned stages. Stage 1 will be conducted to confirm feasibility
and safety of protocol treatment in all patients and separately in the Delayed Primary
Surgery (DPS) patients. The outcome measure for stage 2 will be 9-month progression-free
survival (PFS) rate. The primary outcome measures for stage 3 will be PFS and overall
survival and secondary outcomes will be toxicity, Quality of Life and Health Economics. If
pre-defined levels of deliverability, at stage 1, or activity, at stage 2, are not met then
the research arms will be reconsidered.


Inclusion Criteria:



- Females aged 18 years or more

- Signed informed consent and ability to comply with the protocol

- Histologically confirmed, with core biopsy from a disease site as minimum
requirement (cytology alone is insufficient for diagnosis):

- Epithelial ovarian carcinoma

- Primary peritoneal carcinoma of Müllerian histological type

- Fallopian tube carcinoma

- FIGO stage IC or above, which may be based on clinical and radiological assessment in
patients who have not undergone immediate primary surgery

- Confirmed high-risk histological subtype for patients with FIGO stage IC/IIA disease,
namely:

- High grade serous carcinoma

- Clear cell carcinoma

- Other histological subtype considered poorly differentiated/grade 3

- ECOG Performance Status (PS) 0-2

- Life expectancy > 12 weeks

- Adequate bone marrow function:

- Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/l

- Platelets (Plt) ≥ 100 x 109/l

- Haemoglobin (Hb) ≥ 9g/dl (can be post transfusion)

- Adequate liver function (within 28 days prior to randomisation):

- Serum bilirubin (BR) ≤ 1.5 x ULN

- Serum transaminases ≤ 3 x ULN in the absence of parenchymal liver metastases or
≤ 5 x ULN in the presence of parenchymal liver metastases

- Adequate renal function as defined by GFR (Glomerular Filtration Rate) ≥ 30ml/min.

Exclusion Criteria:

- Non-epithelial ovarian cancer, including malignant mixed Müllerian tumours
(carcinosarcomas)

- Peritoneal cancer that is not of Müllerian origin, including mucinous histology

- Borderline tumours (tumours of low malignant potential)

- Prior systemic anti-cancer therapy for ovarian cancer (for example chemotherapy,
monoclonal antibody therapy, tyrosine kinase inhibitor therapy or hormonal therapy)

- Previous malignancies within 5 years prior to randomisation apart from: adequately
treated carcinoma in-situ of the cervix, breast ductal carcinoma in-situ,
non-melanomatous skin cancer; or previous/synchronous early-stage endometrial cancer
defined as stage IA (FIGO 2009) grade 1 or 2 endometrioid cancers with no
lymphovascular space invasion

- Pre-existing sensory or motor neuropathy grade ≥ 2

- Evidence of any other disease/metabolic dysfunction that in the opinion of the
investigator would put the subject at high-risk of treatment-related complications or
prevent compliance with the trial protocol

- Planned intraperitoneal cytotoxic chemotherapy

- Any previous radiotherapy to the abdomen or pelvis

- Sexually active women of childbearing potential not willing to use adequate
contraception (e.g. oral contraceptives, intrauterine device or barrier method of
contraception in conjunction with spermicidal jelly or surgically sterile) for the
study duration and at least six months afterwards

- Pregnant or lactating women

- Treatment with any other investigational agent prior to protocol defined progression

- Known hypersensitivity to carboplatin, paclitaxel or their excipients (including
cremophor)

- History or clinical suspicion of brain metastases or spinal cord compression. CT/MRI
of the brain is mandatory in the case of suspected brain metastases. Spinal MRI is
mandatory in the case of suspected spinal cord compression. Patients with brain or
meningeal metastases are not eligible

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Stage 1: Feasibility assessed as the number of cycles and dose intensity of protocol treatment delivered per patient.

Outcome Time Frame:

6 months after the 50th patient has been randomised to each arm and 6 months after the 50th patient with a plan to undergo delayed primary surgery has been randomised to each arm

Safety Issue:

No

Authority:

United Kingdom: Medicines and Healthcare Products Regulatory Agency

Study ID:

2010-022209-16

NCT ID:

NCT01654146

Start Date:

June 2011

Completion Date:

Related Keywords:

  • Ovarian Cancer
  • Ovarian cancer
  • Epithelial ovarian carcinoma
  • Fallopian tube carcinoma
  • Primary serous peritoneal carcinoma
  • Gynaecological carcinoma
  • Randomised controlled trial
  • Ovarian Neoplasms

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