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

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

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.

Study Overview

• Status: Completed
• Conditions: Uveal Melanoma
• Intervention / Treatment: Drug: Adjuvant chemotherapy by Fotemustin; Other: Intensive surveillance

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).

• Study Type: Interventional
• Enrollment (Actual): 302
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Clermont-ferrand, France, 63011
    • Centre Jean Perrin
  • Lyon, France, 69373
    • Centre LEON BERARD
  • Nice, France, 06189
    • Centre Antoine Lacassagne
  • Nice, France, 06003
    • CHU Nice
  • Paris, France, 75005
    • Institut Curie
• Switzerland
  • Lausanne, Switzerland, 1011
    • Centre Hospitalier Universitaire Vaudois

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A : Chemotherapy; Adjuvant chemotherapy by Fotemustin 100mg/m²	Drug: Adjuvant 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.; Other Names: Fotemustin
Other: B : Surveillance; Intensive surveillance	Other: Intensive 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.; Other Names: Surveillance

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metastasis-Free survival	Time between patient randomization and metastases occurrence or death	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Time between patient randomization and death	3 years
Safety : incidence of Adverse Events and Serious Adverse Events and laboratory abnormalities	using National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) V3	3 years
Quality of life assessment	Using QLQ-C30 questionary.	Baseline, 6 months and 3 years

Collaborators and Investigators

• Sponsor: Institut Curie
• Collaborators: Servier; UNICANCER

Study record dates

Study Major Dates

• Study Start (Actual): June 23, 2009
• Primary Completion (Actual): June 12, 2020
• Study Completion (Actual): June 12, 2020

Study Registration Dates

• First Submitted: July 21, 2016
• First Submitted That Met QC Criteria: July 22, 2016
• First Posted (Estimate): July 25, 2016

Study Record Updates

• Last Update Posted (Actual): August 31, 2022
• Last Update Submitted That Met QC Criteria: August 30, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Adjuvant chemotherapy; Uveal melanoma; High risk of metastasis; Genomic high risk signature
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Eye Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Uveal Diseases; Neuroendocrine Tumors; Nevi and Melanomas; Eye Neoplasms; Melanoma; Uveal Neoplasms
• Other Study ID Numbers: IC 2008-03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No