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

KRAS Gene Mutation Clinical Trial

— GETUG-AFU19  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02818725
• Other study ID #: GETUG-AFU 19/0903
• Secondary ID: 2009-011882-10
• Status: Completed
• Phase: Phase 3
• Start date: June 2010
• Est. completion date: September 2017

Study information

• Verified date: March 2021
• Source: UNICANCER
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 133
• Est. completion date: September 2017
• Est. primary completion date: September 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Transitional Cell
• Infiltrating Urothelial Carcinoma
• KRAS Gene Mutation

Intervention

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
• Panitumumab
PANITUMUMAB: 6 mg/kg on day 2

Locations

Country	Name	City	State
France	Hopital Saint Andre	Bordeaux
France	Institut Bergonie	Bordeaux
France	Centre Francois Baclesse	Caen
France	Hopital Henri Mondor	Creteil
France	Centre Leon Berard	Lyon
France	Institut Paoli Calmettes	Marseille
France	Centre Alexis Vautrin	Nancy
France	Centre Rene Gauducheau	Nantes
France	Chu de Nimes	Nimes
France	Diaconesses - Croix St Simon	Paris
France	Institut Curie	Paris
France	Pitie Salpetriere	Paris
France	Centre Hospitalier Lyon Sud	Pierre Benite
France	Institut Cancerologie de La Loire	St Priest En Jarez
France	Hopitaux Universitaires	Strasbourg
France	Institut Claudius Regaud	Toulouse
France	Institut Gustave Roussy	Villejuif

Sponsors (1)

Lead Sponsor	Collaborator
UNICANCER

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to progression	Progression-Free Survival at 9 months post-treatment	9 months
Secondary	Toxicities assessment	toxicity (CTC AE v4.0) after end of treatment	24 months
Secondary	Evaluation of response	Recist 1.1	24 months
Secondary	Evaluation of overall survival		24 months
Secondary	Evaluation of time to progression		24 months