ICON8 Trials Programme

Phase 3

• Conditions: Ovarian/gynaecological cancer; Cancer; Malignant neoplasm of ovary

• Registration Number: ISRCTN10356387
• Lead Sponsor: MRC Clinical Trials Unit at UCL (UK)

Brief Summary

2019 Results article in https://www.ncbi.nlm.nih.gov/pubmed/31791688 ICON8 results (added 04/12/2019) 2020 Results article in https://pubmed.ncbi.nlm.nih.gov/32615110/ ICON8 quality-of-life results (added 05/07/2020) 2022 Results article in https://pubmed.ncbi.nlm.nih.gov/35690073/ ICON8 overall survival and progression-free survival results (added 13/06/2022)

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2011-05-27
• Last Update Posted: 8 January 2024
• Study Completion: 2024-12-31

Recruitment & Eligibility

• Status: Ongoing
• Sex: Female
• Target Recruitment: 2144

Inclusion Criteria

Current ICON8 inclusion criteria as of 12/09/2018:
1. Females aged =18 years
2. Signed informed consent and ability to comply with the protocol
3. Histologically confirmed, with core biopsy from a disease site as minimum requirement (cytology alone is insufficient for diagnosis):
3.1. Epithelial ovarian carcinoma
3.2. Primary peritoneal carcinoma of Müllerian histological type
3.3. Fallopian tube carcinoma
3.4. Ovarian carcinosarcoma (malignant mixed Müllerian tumour (MMMT) of the ovary).
4. FIGO (1988) stage IC or above, which may be based on clinical and radiological assessment in patients who have not undergone immediate primary surgery
5. Confirmed high-risk histological subtype for patients with FIGO (1988) stage IC/IIA disease, namely:
5.1. High grade serous carcinoma
5.2. Clear cell carcinoma
5.3. Other histological subtype considered poorly differentiated/grade 3
6. ECOG Performance Status (PS) 0-2
7. Life expectancy >12 weeks
8. Adequate bone marrow function:
8.1. Absolute Neutrophil Count (ANC) =1.5 x 10(9)/l
8.2. Platelets (Plt) =100 x 10(9)/l
8.3. Haemoglobin (Hb) =9 g/dl (can be post transfusion)
9. Adequate liver function:
9.1. Serum bilirubin (BR) =1.5 x ULN
9.2. Serum transaminases =3 x ULN in the absence of parenchymal liver metastases or =5 x ULN in the presence of parenchymal liver metastases
10.Adequate renal function as defined by:
10.1. Directly measured GFR (Glomerular Filtration Rate) = 30 ml/min, or
10.2. Calculated creatinine clearance =60 ml/min
11.Able to start chemotherapy within 8 weeks after immediate primary surgery (where applicable)

Previous ICON8 inclusion criteria:
1. Females aged 18 years and above
2. Signed informed consent and ability to comply with the protocol
3. Histologically confirmed, with core biopsy from a disease site as minimum requirement (cytology alone is insufficient for diagnosis):
3.1. Epithelial ovarian carcinoma
3.2. Primary peritoneal carcinoma of Müllerian histological type
3.3. Fallopian tube carcinoma
4. FIGO stage IC or above, which may be based on clinical and radiological assessment in patients who have not undergone immediate primary surgery
5. Confirmed high-risk histological subtype for patients with FIGO stage IC/IIA disease, namely:
5.1. High grade serous carcinoma
5.2. Clear cell carcinoma
5.3. Other histological subtype considered poorly differentiated/grade 3
6. ECOG Performance Status (PS) 02
7. Life expectancy >12 weeks
8. Adequate bone marrow function:
8.1. Absolute Neutrophil Count > 1.5 x 10^9/l
8.2. Platelets (Plt) > 100 x 10^9/l
8.3. Haemoglobin (Hb) > 9g/dl (can be post transfusion)
9. Adequate liver function (within 28 days prior to randomisation)
9.1. Serum bilirubin = 1.5 x ULN
9.2. Serum transaminases = 3 x ULN in the absence of parenchymal liver metastases or = 5 x ULN in the presence of parenchymal liver metastases
10. Adequate renal function as defined by GFR (Glomerular Filtration Rate) = 30ml/min
11. Target gender: female
12. Lower age limit 18 years

Current ICON8B inclusion criteria as of 12/09/2018:
1. Females aged =18 years
2. Signed informed consent and ability to comply with the protocol
3. Histologically confirmed, with core biopsy from a disease site as minimum requirement (cytology alone is insufficient for diagnosis):
3.1. Epithelial ovarian carcinoma
3.2. Primary peritoneal carcinoma of Müllerian histological type
3.3. Fallopian tube carcinoma
3.4. Ovarian carcinosarcoma (malignant mixed Müllerian tumour (MMMT) of the ovary)
4. Hi

Exclusion Criteria

Current ICON8 exclusion criteria as of 12/09/2018:
1. Non-epithelial ovarian cancer
2. Peritoneal cancer that is not of Müllerian origin, including mucinous histology
3. Borderline tumours (tumours of low malignant potential)
4. Prior systemic anti-cancer therapy for ovarian cancer (for example chemotherapy, monoclonal antibody therapy, tyrosine kinase inhibitor therapy or hormonal therapy)
5. Previous malignancies within 5 years prior to randomisation apart from:
5.1. adequately treated carcinoma in-situ of the cervix, breast ductal carcinoma in-situ, non-melanomatous skin cancer; or
5.2. previous/synchronous early-stage endometrial cancer defined as stage IA (FIGO 2009) grade 1 or 2 endometrioid cancers with no lymphovascular space invasion
6. Pre-existing sensory or motor neuropathy grade =2
7. 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
8. Planned intraperitoneal cytotoxic chemotherapy
9. Planned maintenance treatment with systemic anti-cancer therapy following completion of protocol treatment and prior to protocol defined progression
10. Any previous radiotherapy to the abdomen or pelvis
11. Sexually active women of childbearing potential not willing to use adequate contraception (eg. 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
12. Pregnant or lactating women who are currently breastfeeding
13. Treatment with any other investigational agent prior to protocol defined progression
14. Known hypersensitivity to carboplatin, paclitaxel or their excipients (including cremophor)
15. 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.

Previous ICON8 exclusion criteria:
1. Non-epithelial ovarian cancer, including malignant mixed Müllerian tumours (carcinosarcomas)
2. Peritoneal cancer that is not of Müllerian origin, including mucinous histology
3. Borderline tumours (tumours of low malignant potential)
4. Prior systemic anticancer therapy for ovarian cancer (for example chemotherapy, monoclonal antibody therapy, tyrosine kinase inhibitor therapy or hormonal therapy)
5. Previous malignancies within 5 years prior to randomisation apart from: adequately treated carcinoma insitu of the cervix, breast ductal carcinoma insitu, nonmelanomatous 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
6. Preexisting sensory or motor neuropathy grade =2
7. Evidence of any other disease/metabolic dysfunction that in the opinion of the investigator would put the subject at highrisk of treatment-related complications or prevent compliance with the trial protocol
8. Planned intraperitoneal cytotoxic chemotherapy
9. Any previous radiotherapy to the abdomen or pelvis
10. Sexually active women of childbearing potential not willing to use adequate contraception (eg. oral contraceptives, intrauterine device or barrier method of contraception in conjunction with spermicidal jelly or surgicall

Study & Design

• Study Type: Interventional
• Study Design: Not specified