I-MVAC +/- Panitumumab as First-line Treatment of Advanced Urothelial Carcinoma Without H-Ras Nor K-Ras Mutations (GETUG-AFU19)

Intensified Methotrexate, Vinblastine, Doxorubicin and Cisplatin +/-Panitumumab as First-line Treatment of Advanced Urothelial Carcinoma in Patients Without Harvey Nor Kirsten Rat Sarcoma Viral Oncogene Homolog Mutations. Phase II Study

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

Study Overview

• Status: Completed
• Conditions: KRAS Gene Mutation; Infiltrating Urothelial Carcinoma
• Intervention / Treatment: Drug: Chemotherapy; Drug: Panitumumab

• Study Type: Interventional
• Enrollment (Actual): 133
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Bordeaux, France, 33076
    • Institut Bergonié
  • Bordeaux, France, 33075
    • Hôpital Saint André
  • Caen, France, 14076
    • Centre François Baclesse
  • Creteil, France, 94010
    • Hopital Henri Mondor
  • Lyon, France, 69008
    • Centre Leon Bérard
  • Marseille, France, 13273
    • Institut Paoli Calmettes
  • Nancy, France, 54511
    • Centre Alexis Vautrin
  • Nantes, France, 44800
    • Centre Rene Gauducheau
  • Nimes, France, 30029
    • CHU de Nîmes
  • Paris, France, 75005
    • Institut Curie
  • Paris, France, 75013
    • Pitie Salpetriere
  • Paris, France, 75012
    • Diaconesses - Croix St Simon
  • Pierre Benite, France, 69495
    • Centre Hospitalier Lyon Sud
  • St Priest En Jarez, France, 42270
    • Institut Cancerologie de La Loire
  • Strasbourg, France, 67091
    • Hopitaux Universitaires
  • Toulouse, France, 31052
    • Institut Claudius Regaud
  • Villejuif, France, 94805
    • Institut Gustave Roussy

Participation Criteria

Eligibility Criteria

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

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Chemotherapy; Intensified- Methotrexate Vinblastin Doxorubicin Cisplatin	Drug: 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; Other Names: Intensified-Methotrexate Vinblastine Doxorubicin Cisplatin; I-MVAC
Experimental: Arm B: chemotherapy + panitumumab; Intensified- Methotrexate Vinblastin Doxorubicin Cisplatin +/- panitumumab	Drug: 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; Other Names: Intensified-Methotrexate Vinblastine Doxorubicin Cisplatin; I-MVAC; Drug: Panitumumab; PANITUMUMAB: 6 mg/kg on day 2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to progression	Progression-Free Survival at 9 months post-treatment	9 months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: UNICANCER

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2010
• Primary Completion (Actual): September 1, 2016
• Study Completion (Actual): September 1, 2017

Study Registration Dates

• First Submitted: November 29, 2011
• First Submitted That Met QC Criteria: June 29, 2016
• First Posted (Estimate): June 30, 2016

Study Record Updates

• Last Update Posted (Actual): March 9, 2021
• Last Update Submitted That Met QC Criteria: March 4, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Transitional Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Dermatologic Agents; Antibiotics, Antineoplastic; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Cisplatin; Doxorubicin; Methotrexate; Panitumumab; Vinblastine
• Other Study ID Numbers: GETUG-AFU 19/0903; 2009-011882-10 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No