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

• ClinicalTrials.gov Identifier: NCT02843386
• Recruitment Status: Active, not recruiting
• First Posted: July 25, 2016
• Last Update Posted: April 28, 2017
• Sponsor: Institut Curie
• Collaborators: Servier; UNICANCER
• Information provided by (Responsible Party): Institut Curie

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Uveal Melanoma	Drug: Adjuvant chemotherapy by Fotemustin; Other: Intensive surveillance	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 302 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized Phase III Study Comparing an Adjuvant Chemotherapy With Fotemustin to Intensive Surveillance in Patients With High Risk Uveal Melanoma
• Actual Study Start Date: June 23, 2009
• Estimated Primary Completion Date: May 2020
• Estimated Study Completion Date: November 2020

Arms and Interventions

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 Name: Fotemustin
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 Name: Surveillance

Outcome Measures

Primary Outcome Measures :

1. Metastasis-Free survival [ Time Frame: 3 years ]
   Time between patient randomization and metastases occurrence or death

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

France

Centre Jean Perrin

Clermont-ferrand, France, 63011

Centre Léon Bérard

Lyon, France, 69373

CHU Nice

Nice, France, 06003

Centre Antoine Lacassagne

Nice, France, 06189

Institut Curie

Paris, France, 75005

Switzerland

Centre Hospitalier Universitaire Vaudois

Lausanne, Switzerland, 1011

Sponsors and Collaborators

Institut Curie

Servier

UNICANCER

Investigators

• Principal Investigator: Sophie PIPERNO-NEUMANN, MD; Institut Curie

More Information

• Responsible Party: Institut Curie
• ClinicalTrials.gov Identifier: NCT02843386
• Other Study ID Numbers: IC 2008-03
• First Posted: July 25, 2016
• Last Update Posted: April 28, 2017
• Last Verified: April 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Institut Curie:

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

Additional relevant MeSH terms:

Melanoma; Uveal Neoplasms; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases