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

Phase 3

Completed

• Conditions: Infiltrating Urothelial Carcinoma; KRAS Gene Mutation
• Interventions: Drug: Chemotherapy; Drug: Panitumumab

• Registration Number: NCT02818725
• Lead Sponsor: UNICANCER

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

Detailed Description

Not available

Study Timeline

• Study Start: 2010-06
• Study First Submitted: 2011-11-29
• Study First Submitted QC: 2016-06-29
• Study First Posted: 2016-06-30
• Primary Completion: 2016-09
• Study Completion: 2017-09
• Status Verified: 2021-03
• Last Update Submitted: 2021-03-04
• Last Update Posted: 2021-03-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 133

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Chemotherapy	Chemotherapy	Intensified- Methotrexate Vinblastin Doxorubicin Cisplatin
Arm B: chemotherapy + panitumumab	Chemotherapy	Intensified- Methotrexate Vinblastin Doxorubicin Cisplatin +/- panitumumab
Arm B: chemotherapy + panitumumab	Panitumumab	Intensified- Methotrexate Vinblastin Doxorubicin Cisplatin +/- panitumumab

Primary Outcome Measures

Name	Time	Method
Time to progression	9 months	Progression-Free Survival at 9 months post-treatment

Secondary Outcome Measures

Name	Time	Method
Evaluation of time to progression	24 months
Toxicities assessment	24 months	toxicity (CTC AE v4.0) after end of treatment
Evaluation of response	24 months	Recist 1.1
Evaluation of overall survival	24 months

Trial Locations

Locations (17)

Chu de Nimes; 🇫🇷 Nimes, France

Institut Paoli Calmettes; 🇫🇷 Marseille, France

Hopital Saint Andre; 🇫🇷 Bordeaux, France

Institut Bergonie; 🇫🇷 Bordeaux, France

Centre Hospitalier Lyon Sud; 🇫🇷 Pierre Benite, France

Centre Leon Berard; 🇫🇷 Lyon, France

Diaconesses - Croix St Simon; 🇫🇷 Paris, France

Institut Gustave Roussy; 🇫🇷 Villejuif, France

Institut Curie; 🇫🇷 Paris, France

Hopitaux Universitaires; 🇫🇷 Strasbourg, France

Institut Cancerologie de La Loire; 🇫🇷 St Priest En Jarez, France

Institut Claudius Regaud; 🇫🇷 Toulouse, France

Centre Alexis Vautrin; 🇫🇷 Nancy, France

Hopital Henri Mondor; 🇫🇷 Creteil, France

Centre Francois Baclesse; 🇫🇷 Caen, France

Centre Rene Gauducheau; 🇫🇷 Nantes, France

Pitie Salpetriere; 🇫🇷 Paris, France