Cabazitaxel Activity in Patients With Advanced AdrenoCortical-Carcinoma Progressing After Previous Chemotherapy Lines (CabACC)
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|ClinicalTrials.gov Identifier: NCT03257891|
Recruitment Status : Recruiting
First Posted : August 22, 2017
Last Update Posted : April 11, 2018
|Condition or disease||Intervention/treatment||Phase|
|Adrenocortical Carcinoma||Drug: Cabazitaxel||Phase 2|
CABAZITAXEL ADMINISTRATION Cabazitaxel will be administered at dose of 25 mg/m2 every 3 weeks, administered by IV route in 1 hour, for a maximum of 6 total cycles. The drug will be provided by Sanofi -Aventis S.p.A. Concomitant mitotane therapy will not be permitted however mitotane will be maintained in patients with hormone secreting tumors. Cycle length for cabazitaxel is 3 weeks. New cycles of therapy may not begin until Absolute Neutrophil Count (ANC) ≥1500/mm3, platelet count ≥75 000/mm3, and non-hematological toxicities (except alopecia) have recovered to baseline.
A maximum of 2 weeks delay is allowed between 2 treatment cycles.
PHARMACOKINETIC STUDY Another study aims will be to assess the toxicity of cabazitaxel therapy in ACC patients. As mitotane notoriously interfere with the metabolism of several drugs (11), an ancillary study will be conducted to assess the pharmacokinetic profile of cabazitaxel in the patient population with hormone secreting tumors that will maintain mitotane administration vs patients with non secreting ACC in which mitotane will be stopped. Blood samples will be collected in lithium heparinized tubes at fixed time points before and after drug infusion: Cycles 1 on Day 1 just before infusion, 30 min after start of infusion, 5 min before the end of 1-hour infusion (Tmax), 24 h, 48h and 96 h post-infusion. Cabazitaxel serum concentrations will be measured in plasma using a validated liquid chromatography-tandem mass spectrometry method: the Agilent 1260 Infinity LC equipped with an Agilent 6460 Triple Quadrupole Mass Spectrometer (QQQ) in electrospray mode systems.
STATISTICAL ANALYSIS All data collected at baseline, including recorded and derived variables will be described on all patients by means of summary descriptive statistics: mean, standard deviation, median, min, max, 25th and 75th percentiles for continuous variables; absolute and relative frequency for categorical variables. The relative frequencies will be calculated on the total patients with and without missing data. Whenever possible the data will be described by visit.
Chi square ore Fisher test, when applicable will be employed to compare categorical variables. Student T-test and analysis of variance for parametric or Wilcoxon's matched pairs signed-rank test and Friedman analysis of variance for non parametric data will be used to compare paired data. Simple correlation analysis will be performed by Spearman rho (coefficient of Spearman's rank correlation) for nonparametric distribution. Two-tailed tests will be used for all comparisons and p <0.05. All survival functions will computed using the Kaplan-Meier method. Survival curves will be compared with the log rank test.
CONCOMITANT MEDICATION Concurrent treatment with strong inhibitors and strong inducers of cytochrome P450 3A4 is not permitted. For patients who were receiving treatment with such agents, a 2-week washout period is required prior to randomization. Concurrent participation in another clinical trial or treatment with any other anti-cancer therapy is also not permitted. The Investigator may prescribe any other concomitant medications as deemed necessary.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||25 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||A prospective, non-randomized, multicentre, open label, single arm, phase II study will be conducted in patients with advanced ACC treated with Cabazitaxel|
|Masking:||None (Open Label)|
|Official Title:||Multicenter, Prospective, Non-randomized, Phase II Trial Designed to Evaluate the Activity of Cabazitaxel in Patients With Advanced Adreno-Cortical- Carcinoma Progressing After Previous Chemotherapy Lines|
|Actual Study Start Date :||January 25, 2018|
|Estimated Primary Completion Date :||January 24, 2021|
|Estimated Study Completion Date :||January 24, 2022|
Experimental: Arm 1
patients with advanced Adrenocortical- Carcinoma progressing after previous chemotherapy lines will be treated with Cabazitaxel
Cabazitaxel will be administered every 21 days
- To assess the clinical benefit after 4 months of the cabazitaxel in patients with locally advanced or metastatic ACC who progressed after cytotoxic therapy. [ Time Frame: 4 months ]CT scan evaluated according to RECIST 1.1 criteria
- Assessment of Objective Response Rates (ORR) [ Time Frame: Every cycle (21 days) for a maximum of 6 cycles and for 6 months follow up. Total 1 year ]ORR evaluated by RECIST criteria
- Assessment of overall survival [ Time Frame: Every cycle (21 days) for a maximum of 6 cycles and for 6 months follow up. Total 1 year ]defined as the time from the date of the study start to date of death due to any cause
- Assessment of quality of life [ Time Frame: Every cycle (21 days) for a maximum of 6 cycles and for 6 months follow up. Total 1 year ]EORTC quality of life questionnaire (QLQ)-C30 will be administered to patients
- Assessment of toxicity [ Time Frame: Every cycle (21 days) for a maximum of 6 cycles and for 6 months follow up. Total 1 year ]evaluated by NCI CTCAE V4.03 criteria
- Assessment of hormone response [ Time Frame: Every cycle (21 days) for a maximum of 6 cycles and for 6 months follow up. Total 1 year ]Evaluation of adrenocorticotropic hormone (ACTH), Testosterone, Progesterone, Cortisol, (Deidroepiandrosterone) DHEA-S, 17-hydroxide- progesterone, Androstenedione in serum. Evaluation of 24 hours urinary cortisol.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03257891
|Contact: Alfredo Berruti, MD||030399 ext firstname.lastname@example.org|
|Contact: Salvatore Grisanti, MD, PhD||030399 ext email@example.com|
|Azienda Ospedaliera Spedali Civili di Brescia||Recruiting|
|Brescia, Italy, 25123|
|Principal Investigator:||Alfredo Berruti, MD||Azienda Ospedaliera Spedali Civili di Brescia|