NCT01654146

Brief Summary

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.

Trial Health

55
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,485

participants targeted

Target at P75+ for phase_3 ovarian-cancer

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 1, 2011

Completed
1.1 years until next milestone

First Submitted

Initial submission to the registry

June 20, 2012

Completed
1 month until next milestone

First Posted

Study publicly available on registry

July 31, 2012

Completed
4.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2017

Completed
Last Updated

July 31, 2012

Status Verified

July 1, 2012

Enrollment Period

6 years

First QC Date

June 20, 2012

Last Update Submit

July 26, 2012

Conditions

Ovarian Cancer

Keywords

Ovarian cancerEpithelial ovarian carcinomaFallopian tube carcinomaPrimary serous peritoneal carcinomaGynaecological carcinomaRandomised controlled trial

Outcome Measures

Primary Outcomes (5)

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

    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

  • Stage 1: Safety assessed as the rate of any ≥ grade 3 toxicity experienced per patient.

    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

  • Stage 2: Progression Free Survival rate at 9 months after randomisation

    9 months after first 62 patients randomised per arm

  • Stage 3: Progression Free Survival

    PFS expected 1 year after last patient is randomised. OS expected 3 years after last patient is randomised.

  • Stage 3: Overall Survival

    PFS expected 1 year after last patient is randomised. OS expected 3 years after last patient is randomised.

Secondary Outcomes (3)

  • Stage 3: Toxicity assessed by number of participants with adverse events

    Expected 1 year and 3 years after last patient is randomised.

  • Stage 3: Quality of Life

    Expected 1 year and 3 years after last patient is randomised.

  • Stage 3: Health Economics

    Expected 1 year and 3 years after last patient is randomised.

Study Arms (3)

Arm 1 (Control Arm)

ACTIVE COMPARATOR

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

Drug: CarboplatinDrug: Paclitaxel

Arm 2 (Research arm)

EXPERIMENTAL

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

Drug: CarboplatinDrug: Paclitaxel

Arm 3 (Research arm)

EXPERIMENTAL

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

Drug: CarboplatinDrug: Paclitaxel

Interventions

CarboplatinDRUG

AUC5 by intravenous infusion over 30-60 minutes

Arm 1 (Control Arm)Arm 2 (Research arm)
PaclitaxelDRUG

175mg/m2 by intravenous infusion over 3 hours

Arm 1 (Control Arm)

Eligibility Criteria

Age18 Years+
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • +6 more criteria

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Medical Research Council Clinical Trials Unit

London, WC2B 6NH, United Kingdom

RECRUITING

Related Publications (4)

  • 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.

    PMID: 37075255DERIVED

  • 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.

    PMID: 35690073DERIVED

  • 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.

    PMID: 33357510DERIVED

  • 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.

    PMID: 32615110DERIVED

MeSH Terms

Conditions

Ovarian NeoplasmsCarcinoma, Ovarian EpithelialFallopian Tube Neoplasms

Interventions

CarboplatinPaclitaxel

Condition Hierarchy (Ancestors)

Endocrine Gland NeoplasmsNeoplasms by SiteNeoplasmsOvarian DiseasesAdnexal DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital Neoplasms, FemaleUrogenital NeoplasmsGenital DiseasesEndocrine System DiseasesGonadal DisordersCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeFallopian Tube Diseases

Intervention Hierarchy (Ancestors)

Coordination ComplexesOrganic ChemicalsTaxoidsCyclodecanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsDiterpenesTerpenes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER GOV
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Medical Research Council

Study Record Dates

First Submitted

June 20, 2012

First Posted

July 31, 2012

Study Start

June 1, 2011

Primary Completion

June 1, 2017

Last Updated

July 31, 2012

Record last verified: 2012-07

Locations

GB(1)