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

Primary Purpose

Uveal Melanoma

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Adjuvant chemotherapy by Fotemustin

Intensive surveillance

About this trial

This is an interventional treatment trial for Uveal Melanoma focused on measuring Uveal melanoma, High risk of metastasis, Genomic high risk signature, Adjuvant chemotherapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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
Age ≥ 18 years and ECOG Performance Status ≤ 2
No prior chemotherapy or history of invasive cancer < 5years
No metastases
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:

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.
Contraindication to Fotemustine administration
Hematological function : Hb < 10g/dL, absolute neutrophil count < 2,000/mm3, and platelets < 100,000/mm3
Biochemistry results :Total bilirubin and AST/ALT > 1,5 UNL (Upper Normal Limit)
Creatinine > 1,5 UNL (Upper Normal Limit)
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.

Sites / Locations

Centre Jean Perrin
Centre Léon Bérard
CHU Nice
Centre Antoine Lacassagne
Institut Curie
Centre Hospitalier Universitaire Vaudois

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Other

Arm Label

A : Chemotherapy

B : Surveillance

Arm Description

Adjuvant chemotherapy by Fotemustin 100mg/m²

Intensive surveillance

Outcomes

Primary Outcome Measures

Metastasis-Free survival

Time between patient randomization and metastases occurrence or death

Secondary Outcome Measures

Overall Survival

Time between patient randomization and death

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

Quality of life assessment

Using QLQ-C30 questionary.

Full Information

NCT ID

NCT02843386

First Posted

July 21, 2016

Last Updated

August 30, 2022

Sponsor

Institut Curie

Collaborators

Servier, UNICANCER

1. Study Identification

Unique Protocol Identification Number

NCT02843386

Brief Title

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

Acronym

FOTEADJ

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2022

Overall Recruitment Status

Completed

Study Start Date

June 23, 2009 (Actual)

Primary Completion Date

June 12, 2020 (Actual)

Study Completion Date

June 12, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Institut Curie

Collaborators

Servier, UNICANCER

4. Oversight

Data Monitoring Committee

Yes

5. 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.

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Uveal Melanoma

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

302 (Actual)

8. Arms, Groups, and Interventions

Arm Title

A : Chemotherapy

Arm Type

Experimental

Arm Description

Adjuvant chemotherapy by Fotemustin 100mg/m²

Arm Title

B : Surveillance

Arm Type

Other

Arm Description

Intensive surveillance

Intervention Type

Drug

Intervention Name(s)

Adjuvant chemotherapy by Fotemustin

Other Intervention Name(s)

Fotemustin

Intervention Description

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.

Intervention Type

Other

Intervention Name(s)

Intensive surveillance

Other Intervention Name(s)

Surveillance

Intervention Description

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

Primary Outcome Measure Information:

Title

Metastasis-Free survival

Description

Time between patient randomization and metastases occurrence or death

Time Frame

3 years

Secondary Outcome Measure Information:

Title

Overall Survival

Description

Time between patient randomization and death

Time Frame

3 years

Title

Safety : incidence of Adverse Events and Serious Adverse Events and laboratory abnormalities

Description

using National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) V3

Time Frame

3 years

Title

Quality of life assessment

Description

Using QLQ-C30 questionary.

Time Frame

Baseline, 6 months and 3 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Age ≥ 18 years and ECOG Performance Status ≤ 2 No prior chemotherapy or history of invasive cancer < 5years No metastases 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: 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. Contraindication to Fotemustine administration Hematological function : Hb < 10g/dL, absolute neutrophil count < 2,000/mm3, and platelets < 100,000/mm3 Biochemistry results :Total bilirubin and AST/ALT > 1,5 UNL (Upper Normal Limit) Creatinine > 1,5 UNL (Upper Normal Limit) 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Sophie PIPERNO-NEUMANN, MD

Organizational Affiliation

Institut Curie

Official's Role

Principal Investigator

Facility Information:

Facility Name

Centre Jean Perrin

City

Clermont-ferrand

ZIP/Postal Code

63011

Country

France

Facility Name

Centre Léon Bérard

City

Lyon

ZIP/Postal Code

69373

Country

France

Facility Name

CHU Nice

City

Nice

ZIP/Postal Code

06003

Country

France

Facility Name

Centre Antoine Lacassagne

City

Nice

ZIP/Postal Code

06189

Country

France

Facility Name

Institut Curie

City

Paris

ZIP/Postal Code

75005

Country

France

Facility Name

Centre Hospitalier Universitaire Vaudois

City

Lausanne

ZIP/Postal Code

1011

Country

Switzerland

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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