Clinical trial NCT02818725: I-MVAC +/- Panitumumab as First-line Treatment of Advanced Urothelial Carcinoma Without H-Ras Nor K-Ras Mutations
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Infiltrating Urothelial Carcinoma
KRAS Gene Mutation
Lead sponsor: UNICANCER
Sponsor class: OTHER
First posted: 2016-06-30
Enrollment: 133
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


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.

Primary outcomes:
measure: Time to progression
timeFrame: 9 months
Secondary outcomes:
measure: Toxicities assessment
timeFrame: 24 months
measure: Evaluation of response
timeFrame: 24 months
measure: Evaluation of overall survival
timeFrame: 24 months
measure: Evaluation of time to progression
timeFrame: 24 months
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Hopital Saint Andre
city: Bordeaux
country: France
facility: Institut Bergonie
city: Caen
country: France
facility: Centre Francois Baclesse
city: Creteil
country: France
facility: Hopital Henri Mondor
city: Lyon
country: France
facility: Centre Leon Berard
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Nancy
country: France
facility: Centre Alexis Vautrin
city: Nantes
country: France
facility: Centre Rene Gauducheau
city: Nimes
country: France
facility: Chu de Nimes
city: Paris
country: France
facility: Institut Curie
city: Paris
country: France
facility: Diaconesses - Croix St Simon
city: Paris
country: France
facility: Pitie Salpetriere
city: Pierre Benite
country: France
facility: Centre Hospitalier Lyon Sud
city: St Priest En Jarez
country: France
facility: Institut Cancerologie de La Loire
city: Strasbourg
country: France
facility: Hopitaux Universitaires
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
References: