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

Uveal Melanoma Clinical Trial

— FOTEADJ  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02843386
• Other study ID #: IC 2008-03
• Status: Completed
• Phase: Phase 3
• Start date: June 23, 2009
• Est. completion date: June 12, 2020

Study information

• Verified date: August 2022
• Source: Institut Curie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 302
• Est. completion date: June 12, 2020
• Est. primary completion date: June 12, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Melanoma
• Uveal Melanoma
• Uveal Neoplasms

Intervention

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:
• 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.

Locations

Country	Name	City	State
France	Centre Jean Perrin	Clermont-ferrand
France	Centre Léon Bérard	Lyon
France	Centre Antoine Lacassagne	Nice
France	CHU Nice	Nice
France	Institut Curie	Paris
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne

Sponsors (3)

Lead Sponsor	Collaborator
Institut Curie	Servier, UNICANCER

Countries where clinical trial is conducted

France,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Metastasis-Free survival	Time between patient randomization and metastases occurrence or death	3 years
Secondary	Overall Survival	Time between patient randomization and death	3 years
Secondary	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
Secondary	Quality of life assessment	Using QLQ-C30 questionary.	Baseline, 6 months and 3 years