Clinical trial NCT01745757: Cohort Study of Prospective Validation of Predictive Factors and Biological Imaging of Response to Bevacizumab and Paclitaxel in Patients With Metastatic Breast Cancer
Official title: Cohort Study of Prospective Validation of Predictive Factors and Biological Imaging of Response to Bevacizumab (AVASTIN ®) in Combination With Weekly Paclitaxel Chemotherapy in First Line Treatment Patients With Metastatic Breast Cancer
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Metastatic
Breast Cancer
Lead sponsor: UNICANCER
Sponsor class: OTHER
First posted: 2012-12-10
Enrollment: 510
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: metastatic breast cancer

Brief summary: Bevacizumab plus chemotherapy improves response rates and prolongs PFS when used as first- and second-line therapy for advanced breast cancer. However, bevacizumab has not improved OS in the individual studies currently reported. In Europe, EMA has maintained its indication associated with weekly paclitaxel in first line metastatic breast cancer and more recently with capecitabine based on RIBBON 1 trial's results.

The identification of patient subsets that receive the most clinical benefit would enable more specific treatment administration of bevacizumab and allow patients unlikely to benefit the opportunity to seek other treatment modalities. Unfortunately, despite efforts to identify patient subsets with a differential benefit from bevacizumab, no validated biomarkers have been defined.

The Avastin cohort is a unique opportunity to investigate various biological and imaging parameters which could be related to clinical benefit of the combination of bevacizumab and weekly paclitaxel in first line metastatic breast cancer in a homogeneously treated population in French cancer centers. This trial will gather the expertise of several translational research platforms of different cancer centers from the UNICANCER consortium.


Eligibility criteria: Inclusion Criteria:

* Male or female ≥18 years old.
* Histologically confirmed breast adenocarcinoma, metastatic (measurable or unmeasurable lesion), HER2 negative (on the last tumor tissue analyzed), Patient to receive first-line chemotherapy paclitaxel and bevacizumab in a weekly manner as recommended by the EMEA.
* Hormone receptor status known
* Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
* Life expectancy ≥12 weeks.
* Women of childbearing age (except amenorrhea of at least 24 months) must have a negative pregnancy test serum within 28 days before starting treatment. In the absence of serum test, a urine pregnancy test (within 7 days before the first dose of bevacizumab) is required.
* Informed consent form duly signed and dated by patient

Exclusion Criteria:

* Prior chemotherapy for metastatic disease ;
* Concomitant hormone therapy
* The patient must not have undergone radiation therapy for the treatment of metastatic disease (except cases of analgesic radiotherapy for bone pain due to metastases).
* Pregnant or nursing woman or woman of childbearing age (except amenorrhea for at least 24 months) who does not use an effective nonhormonal contraceptive method (intrauterine device, barrier method associated with the use of a spermicidal gel or surgical castration) for the duration of the study and 6 months after paclitaxel administration and / or bevacizumab.
* Man who does not accept to use effective contraception during the study period and 6 months after paclitaxel administration and / or bevacizumab.
* Known hypersensitivity to paclitaxel and / or to bevacizumab or to any excipients.
* Patient unable to undergo medical test for geographical, social or psychological reasons.
* Patient deprived of liberty or placed under the authority of a tutor

Primary outcomes:
measure: Measure of the initial rates and changes in CEC / CLC (Biological study) and measure of the visceral fat (imaging study) as predictors of progression-free survival (PFS) and response to bevacizumab and paclitaxel
timeFrame: 2 years
Secondary outcomes:
measure: Identification of new biomarkers as predictive factors of progression free survival (PFS), overall survival (OS) and of response to bevacizumab and paclitaxel.
timeFrame: 2 years
measure: Quality of Life assessment
timeFrame: 2 years
measure: The Biomarkers selected from our biological, proteomic and pharmacogenetic studies will be correlated to the safety.
timeFrame: 2 years
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Institut Bergonie
city: Caen
country: France
facility: Centre Francois Baclesse
city: Clermont Ferrand
country: France
facility: Centre Jean Perrin
city: Dijon
country: France
facility: Centre Georges Francois Leclerc
city: Grenoble
country: France
facility: CHU Grenoble
city: Lyon
country: France
facility: Centre Leon Berard
city: Marseille
country: France
facility: Hôpital Européen
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Montpellier
country: France
facility: Centre Val d'Aurelle
city: Nantes
country: France
facility: Centre Catherine de Sienne
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Paris
country: France
facility: Institut Curie
city: Reims
country: France
facility: Institut Jean Godinot
city: Roanne
country: France
facility: Centre Hospitalier
city: Saint Cloud
country: France
facility: Institut Curie
city: Strasbourg
country: France
facility: Centre Paul Strauss
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Vandoeuvre les Nancy
country: France
facility: Centre Alexis Vautrin
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: Institut Curie Paris
name: Jean-Yves PIERGA, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bortolini Silveira A, Bidard FC, Tanguy ML, Girard E, Tredan O, Dubot C, Jacot W, Goncalves A, Debled M, Levy C, Ferrero JM, Jouannaud C, Rios M, Mouret-Reynier MA, Dalenc F, Hego C, Rampanou A, Albaud B, Baulande S, Berger F, Lemonnier J, Renault S, Desmoulins I, Proudhon C, Pierga JY. Multimodal liquid biopsy for early monitoring and outcome prediction of chemotherapy in metastatic breast cancer. NPJ Breast Cancer. 2021 Sep 9;7(1):115. doi: 10.1038/s41523-021-00319-4.
citation: Gal J, Milano G, Brest P, Ebran N, Gilhodes J, Llorca L, Dubot C, Romieu G, Desmoulins I, Brain E, Goncalves A, Ferrero JM, Cottu PH, Debled M, Tredan O, Chamorey E, Merlano MC, Lemonnier J, Etienne-Grimaldi MC, Pierga JY. VEGF-Related Germinal Polymorphisms May Identify a Subgroup of Breast Cancer Patients with Favorable Outcome under Bevacizumab-Based Therapy-A Message from COMET, a French Unicancer Multicentric Study. Pharmaceuticals (Basel). 2020 Nov 23;13(11):414. doi: 10.3390/ph13110414.
citation: Vasseur A, Cabel L, Tredan O, Chevrier M, Dubot C, Lorgis V, Jacot W, Goncalves A, Debled M, Levy C, Ferrero JM, Jouannaud C, Luporsi E, Mouret-Reynier MA, Dalenc F, Lemonnier J, Savignoni A, Tanguy ML, Bidard FC, Pierga JY. Prognostic value of CEC count in HER2-negative metastatic breast cancer patients treated with bevacizumab and chemotherapy: a prospective validation study (UCBG COMET). Angiogenesis. 2020 May;23(2):193-202. doi: 10.1007/s10456-019-09697-7. Epub 2019 Nov 26.