ICON8: Weekly Chemotherapy in Ovarian Cancer

NCT ID: NCT01654146

Last Updated: 2012-07-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

1485 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-06-30

Brief Summary

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The purpose of this study is to determine if weekly chemotherapy (i.e. giving paclitaxel or carboplatin at a lower dose every week) is more effective than standard chemotherapy (paclitaxel and carboplatin given once every three weeks over 18 weeks) in treating ovarian cancer. The investigators also want to see if weekly chemotherapy causes more or fewer side-effects than standard chemotherapy.

Detailed Description

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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.

Conditions

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Ovarian Cancer

Keywords

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm 1 (Control Arm)

Carboplatin and paclitaxel on day 1 of a 21-day cycle for 6 cycles

Group Type ACTIVE_COMPARATOR

Carboplatin

Intervention Type DRUG

AUC5 by intravenous infusion over 30-60 minutes

Paclitaxel

Intervention Type DRUG

175mg/m2 by intravenous infusion over 3 hours

Arm 2 (Research arm)

Carboplatin on day 1 and dose-fractionated weekly paclitaxel on day 1, 8 and 15 of a 21-day cycle for 6 cycles

Group Type EXPERIMENTAL

Carboplatin

Intervention Type DRUG

AUC5 by intravenous infusion over 30-60 minutes

Paclitaxel

Intervention Type DRUG

80mg/m2 by intravenous infusion over 1 hour

Arm 3 (Research arm)

Dose-fractionated weekly carboplatin and weekly paclitaxel on day 1, 8 and 15 of a 21-day cycle for 6 cycles.

Group Type EXPERIMENTAL

Carboplatin

Intervention Type DRUG

AUC2 by intravenous infusion over 30-60 minutes

Paclitaxel

Intervention Type DRUG

80mg/m2 by intravenous infusion over 1 hour

Interventions

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Carboplatin

AUC5 by intravenous infusion over 30-60 minutes

Intervention Type DRUG

Carboplatin

AUC2 by intravenous infusion over 30-60 minutes

Intervention Type DRUG

Paclitaxel

175mg/m2 by intravenous infusion over 3 hours

Intervention Type DRUG

Paclitaxel

80mg/m2 by intravenous infusion over 1 hour

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Cancer Research UK

OTHER

Sponsor Role collaborator

Medical Research Council

OTHER_GOV

Sponsor Role lead

Responsible Party

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Medical Research Council

Medical Research Council

Responsibility Role SPONSOR_INVESTIGATOR

Locations

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Medical Research Council Clinical Trials Unit

London, , United Kingdom

Site Status RECRUITING

Countries

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United Kingdom

Facility Contacts

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Monique Tomiczek

Role: primary

Laura Farrelly

Role: backup

References

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Colomban O, Clamp A, Cook A, McNeish IA, You B. Benefit From Fractionated Dose-Dense Chemotherapy in Patients With Poor Prognostic Ovarian Cancer: ICON-8 Trial. JCO Clin Cancer Inform. 2023 Apr;7:e2200188. doi: 10.1200/CCI.22.00188.

Reference Type DERIVED
PMID: 37075255 (View on PubMed)

Clamp AR, James EC, McNeish IA, Dean A, Kim JW, O'Donnell DM, Gallardo-Rincon D, Blagden S, Brenton J, Perren TJ, Sundar S, Lord R, Dark G, Hall M, Banerjee S, Glasspool RM, Hanna CL, Williams S, Scatchard KM, Nam H, Essapen S, Parkinson C, McAvan L, Swart AM, Popoola B, Schiavone F, Badrock J, Fananapazir F, Cook AD, Parmar M, Kaplan R, Ledermann JA. Weekly dose-dense chemotherapy in first-line epithelial ovarian, fallopian tube, or primary peritoneal cancer treatment (ICON8): overall survival results from an open-label, randomised, controlled, phase 3 trial. Lancet Oncol. 2022 Jul;23(7):919-930. doi: 10.1016/S1470-2045(22)00283-2. Epub 2022 Jun 9.

Reference Type DERIVED
PMID: 35690073 (View on PubMed)

Morgan RD, McNeish IA, Cook AD, James EC, Lord R, Dark G, Glasspool RM, Krell J, Parkinson C, Poole CJ, Hall M, Gallardo-Rincon D, Lockley M, Essapen S, Summers J, Anand A, Zachariah A, Williams S, Jones R, Scatchard K, Walther A, Kim JW, Sundar S, Jayson GC, Ledermann JA, Clamp AR. Objective responses to first-line neoadjuvant carboplatin-paclitaxel regimens for ovarian, fallopian tube, or primary peritoneal carcinoma (ICON8): post-hoc exploratory analysis of a randomised, phase 3 trial. Lancet Oncol. 2021 Feb;22(2):277-288. doi: 10.1016/S1470-2045(20)30591-X. Epub 2020 Dec 22.

Reference Type DERIVED
PMID: 33357510 (View on PubMed)

Blagden SP, Cook AD, Poole C, Howells L, McNeish IA, Dean A, Kim JW, O'Donnell DM, Hook J, James EC, White IR, Perren T, Lord R, Dark G, Earl HM, Hall M, Kaplan R, Ledermann JA, Clamp AR. Weekly platinum-based chemotherapy versus 3-weekly platinum-based chemotherapy for newly diagnosed ovarian cancer (ICON8): quality-of-life results of a phase 3, randomised, controlled trial. Lancet Oncol. 2020 Jul;21(7):969-977. doi: 10.1016/S1470-2045(20)30218-7.

Reference Type DERIVED
PMID: 32615110 (View on PubMed)

Other Identifiers

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10356387

Identifier Type: OTHER

Identifier Source: secondary_id

2010-022209-16

Identifier Type: -

Identifier Source: org_study_id