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Comparison Between Fotemustin to Intensive Surveillance in Patients With High Risk Uveal Melanoma

Randomized Phase III Study Comparing an Adjuvant Chemotherapy With Fotemustin to Intensive Surveillance in Patients With High Risk Uveal Melanoma

Status
Completed
Phases
Phase 3
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT02843386
Acronym
FOTEADJ
Enrollment
302
Registered
2016-07-25
Start date
2009-06-23
Completion date
2020-06-12
Last updated
2022-08-31

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Uveal Melanoma

Keywords

Uveal melanoma, High risk of metastasis, Genomic high risk signature, Adjuvant chemotherapy

Brief summary

After the local treatment of the primary tumor (protonbeam-therapy, enucleation, external radiotherapy) patients with high risk of metastasis are randomized between: * Adjuvant chemotherapy with Fotemustin. * Observation Both groups are followed during 3 years for Metastasis- Free Survival, safety and tolerance of Fotemustin, quality of life, and Overall Survival.

Detailed description

High risk uveal melanoma is defined by : * Clinical criteria: Largest Tumor Diameter ≥ 15 mm with extra scleral extension and/or retinal detachment or Largest Tumor Diameter ≥ 18 mm AND/ OR * Genomic high risk signature (aCGH +/-LOH): Monosomy 3 or partial deletion of 3p associated with any 8 gain. Treatment schedule : * Induction: Fotemustin 100 mg/m², D1-D8-D15, 1 hour IV infusion, 1 cycle * Maintenance : restart on D50, Fotemustine : 100 mg/m², 1 hour IV infusion, D1 D21, 5 cycles. Both groups are followed during 3 years for Metastasis- Free Survival, safety and tolerance of Fotemustin, quality of life, and Overall Survival. Note :Based on the second interim analysis showing futility, and no chance to observe any significant statistical difference at the end of the study, the Independent Data Monitoring Committee recommended to stop randomization and amend the protocol to propose an interventional surveillance to high-risk patients as per protocol (April 2016).

Interventions

DRUGAdjuvant chemotherapy by Fotemustin

Fotemustin is given for 6 cycles : * One Induction cycle: Fotemustin 100 mg/m², 1 hour IV infusion, D1D8D15, 5 week rest period, restart on D50. * Five Maintenance cycles: Fotemustin 100 mg/m², 1 hour IV infusion, D1-D21.

OTHERIntensive surveillance

Intensive surveillance * Total duration: 3 years. * liver functional tests/3 months, - liver MRI or CT-scan/6 months, - whole body CT-scan/12 months.

Sponsors

Servier
CollaboratorINDUSTRY
UNICANCER
CollaboratorOTHER
Institut Curie
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

Inclusion criteria

1. High risk uveal melanoma, defined by : * Clinical criteria: Largest Tumor Diameter ≥ 15 mm with extrascleral extension and/or retinal detachment or Largest Tumor Diameter ≥ 18 mm AND/OR * Genomic high risk signature (cCGH +/- LOH) : Monosomy 3 or partial deletion of 3p and any 8 gain, from enucleation, transscleral or transvitreal samples 2. Age ≥ 18 years and ECOG Performance Status ≤ 2 3. No prior chemotherapy or history of invasive cancer \< 5years 4. No metastases 5. Local treatment for the primary tumour (surgery and/or radiotherapy) achieved ≤ 30 days from randomization, chemotherapy to begin within 15 days. 6 - Contraception in women of child-bearing potential 7- Written informed consent 8- Patients with French Social Security in compliance with the French law relating to biomedical research. Non-Inclusion Criteria: 1. Largest Tumor Diameter \< 15 mm or Largest Tumor Diameter 15-18 mm without extrascleral extension and/or retinal detachment, in the absence of genomic alteration as defined per protocol or in the absence of Fine Needle Aspiration biopsy for genomic risk assessment. 2. Contraindication to Fotemustine administration 3. Hematological function : Hb \< 10g/dL, absolute neutrophil count \< 2,000/mm3, and platelets \< 100,000/mm3 4. Biochemistry results :Total bilirubin and AST/ALT \> 1,5 UNL (Upper Normal Limit) 5. Creatinine \> 1,5 UNL (Upper Normal Limit) 6. Pregnant and/or breastfeeding women. 8 - Previous history of cancer excepting in situ cervical carcinoma or cutaneous basal carcinoma. 7- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, viral or other hepatitis or cirrhosis, or psychiatric illness/social situation that would interfere with the protocol or limit compliance with study requirements.

Design outcomes

Primary

MeasureTime frameDescription
Metastasis-Free survival3 yearsTime between patient randomization and metastases occurrence or death

Secondary

MeasureTime frameDescription
Overall Survival3 yearsTime between patient randomization and death
Safety : incidence of Adverse Events and Serious Adverse Events and laboratory abnormalities3 yearsusing National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) V3
Quality of life assessmentBaseline, 6 months and 3 yearsUsing QLQ-C30 questionary.

Countries

France, Switzerland

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 26, 2026