I-MVAC +/- Panitumumab as First-line Treatment of Advanced Urothelial Carcinoma Without H-Ras Nor K-Ras Mutations

NCT ID: NCT02818725

Last Updated: 2021-03-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 133 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-06-30
• Study Completion Date: 2017-09-30

Brief Summary

OBJECTIVES OF THE TRIAL

Primary objective

Evaluation of efficacy in terms of progression-free survival at 9 months of the combination of intensified methotrexate, vinblastine, doxorubicin and cisplatin with or without panitumumab as first-line treatment of advanced urothelial carcinoma in patients without Harvey nor Kirsten rat sarcoma viral oncogene homolog mutations.

Secondary objectives

• To assess toxicity
• To assess response rate
• To assess overall survival
• To assess time to progression
• To study the correlation between response rate, time to progression, overall survival and biological parameters

Conditions

Infiltrating Urothelial Carcinoma; KRAS Gene Mutation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Chemotherapy

Intensified- Methotrexate Vinblastin Doxorubicin Cisplatin

Group Type: ACTIVE_COMPARATOR

Chemotherapy

Intervention Type: DRUG

METHOTREXATE: 30 mg/m² on day 1 VINBLASTINE: 3 mg/m² on day 2 DOXORUBICIN: 30 mg/m² on day 2 CISPLATIN: 70 mg/m² on day 2

Arm B: chemotherapy + panitumumab

Intensified- Methotrexate Vinblastin Doxorubicin Cisplatin +/- panitumumab

Group Type: EXPERIMENTAL

Chemotherapy

Intervention Type: DRUG

METHOTREXATE: 30 mg/m² on day 1 VINBLASTINE: 3 mg/m² on day 2 DOXORUBICIN: 30 mg/m² on day 2 CISPLATIN: 70 mg/m² on day 2

Panitumumab

Intervention Type: DRUG

PANITUMUMAB: 6 mg/kg on day 2

Interventions

Chemotherapy

METHOTREXATE: 30 mg/m² on day 1 VINBLASTINE: 3 mg/m² on day 2 DOXORUBICIN: 30 mg/m² on day 2 CISPLATIN: 70 mg/m² on day 2

Intervention Type: DRUG

Panitumumab

PANITUMUMAB: 6 mg/kg on day 2

Intervention Type: DRUG

Other Intervention Names

Intensified-Methotrexate Vinblastine Doxorubicin Cisplatin; I-MVAC

Eligibility Criteria

Inclusion Criteria

1. Primary tumour of the bladder or upper urinary tract

2. Histologically confirmed infiltrating urothelial carcinoma (epidermoid and/or glandular forms are accepted)

3. Patients without Harvey and Kirsten-rat sarcoma viral oncogene homolog mutations

4. Advanced disease defined by a locally advanced stage (T4 and/or N+) ineligible for surgical resection, or a metastatic stage (M1)

5. Patients with at least 1 evaluable lesion as per Response evaluation criteria in solid tumors version 1.1 (RECIST v1.1)

6. 18 ≤ age ≤ 75 years

7. General condition 0 or 1 as per the WHO scale

8. Absence of previous chemotherapy for advanced disease (chemotherapy with gemcitabine and platinum salt delivered as an adjuvant is accepted if this ended more than a year ago)

9. Haematological function: Haemoglobin >11 g/dl, neutrophils ≥1500/mm³, platelets ≥100,000/mm³

10. Liver function: Grade* 0 Aspartate aminotransferase and Alanine aminotransferase (< grade* 3 for liver metastases), grade* 0 alkaline phosphatases, normal bilirubin

11. Renal function: calculated (or measured) creatinine clearance >60 ml/min

12. Patients covered by a social security scheme

13. Patient having read the information sheet and signed the informed consent form.

Exclusion Criteria

1. Pure adenocarcinoma or pure epidermoid carcinoma or mixed or pure small-cell neuroendocrine carcinoma

2. Previous treatment with one of the following molecules: methotrexate, vinblastine, doxorubicin or Epidermal Growth Factor inhibitor

3. History of interstitial pneumonitis or pulmonary fibrosis

4. History of cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, uncontrolled serious cardiac arrhythmia) in the year prior to randomisation (≤1 year)

5. Ventricular ejection fraction <50%

6. Blood calcium and/or magnesium ≥ grade* 1

7. History of cancer in the 5 years prior to entry in the trial other than basal cell skin cancer or in situ epithelioma of the cervix,

8. Treatment with radiotherapy for analgesic purposes (unless treatment was discontinued at least 15 days prior to inclusion in the trial)

9. Potential allergy to panitumumab

10. Male or female patients not agreeing to use an effective method of contraception throughout the duration of treatment and for 6 months after treatment discontinuation

11. Pregnant women, or female subjects liable to become pregnant or currently breast-feeding,

12. Patient already included in another therapeutic trial on an investigational medicinal product,

13. Persons deprived of their freedom or under judicial protection (including guardianship),

14. Unable to receive medical follow-up during the trial owing to geographical, social or psychological reasons.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

UNICANCER

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Hopital Saint Andre

Bordeaux, , France

Institut Bergonie

Bordeaux, , France

Centre Francois Baclesse

Caen, , France

Hopital Henri Mondor

Créteil, , France

Centre Leon Berard

Lyon, , France

Institut Paoli Calmettes

Marseille, , France

Centre Alexis Vautrin

Nancy, , France

Centre Rene Gauducheau

Nantes, , France

Chu de Nimes

Nîmes, , France

Institut Curie

Paris, , France

Diaconesses - Croix St Simon

Paris, , France

Pitie Salpetriere

Paris, , France

Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

Institut Cancerologie de La Loire

Saint-Priest-en-Jarez, , France

Hopitaux Universitaires

Strasbourg, , France

Institut Claudius Regaud

Toulouse, , France

Institut Gustave Roussy

Villejuif, , France

Countries

France

Other Identifiers

2009-011882-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GETUG-AFU 19/0903

Identifier Type: -

Identifier Source: org_study_id