Adrenocortical CarcinomaPhase 2CabACCNCT03257891
Cabazitaxel Activity in Patients With Advanced AdrenoCortical-Carcinoma Progressing After Previous Chemotherapy Lines
A Phase 2 study testing Cabazitaxel in people with Adrenocortical Carcinoma, run by Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia at 1 site in Italy.
Trial summary
Adrenocortical cancer (ACC) is a rare aggressive tumor. The treatment of metastatic ACC is challenging and the current available treatments are mitotane, chemotherapy or the combination of both. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adrenocortical Carcinoma
- What is being tested?
- Cabazitaxel
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteItaly
- Study dates
- 25 Jan 2018to 24 Jan 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed diagnosis of ACC
- Locally advanced or metastatic disease not amenable to radical surgery resection
- Radiologically monitorised disease
- Progressing disease after one to three cytotoxic chemotherapy regimes (including a platin-based protocol)
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Life expectancy ≥ 3 months
Show all 12Show fewer
- Age ≥ 18 years
- Adequate bone marrow reserve (neutrophils ≥ 1500/mm³ and platelets > 100.000/mm³)
- Effective contraception in pre-menopausal female and male patients
- Patient´s written informed consent
- Ability to comply with the protocol procedures
- Mitotane intake should be stopped one months before the study entry
Who cannot join
- History of prior malignancy, except for cured non-melanoma skin cancer, cured in situ cervical carcinoma, or other treated malignancies with no evidence of disease for at least three years.
- Serum creatinine > 1.5 x ULN or hepatic insufficiency, Hemoglobin <10.0 g/dL;
- Total bilirubin >1x ULN, Creatinine < 1.5 ULN;
- Decompensated heart failure (ejection fraction <45%), myocardial infarction or revascularization procedure during the last 6 months, unstable angina pectoris, uncontrolled cardiac arrhythmia
- Pregnancy or breast feeding
- Any other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration, or which, in the judgment of the investigator, would make the patient inappropriate for entry into this study
Show all 11Show fewer
- Patients with serum levels of mitotane (evaluated one week before the study start) in the therapeutic range (14-20 mcg/ml).History of severe hypersensitivity reaction (≥grade 3) to docetaxel
- History of severe hypersensitivity reaction (≥grade 3) to polysorbate 80 containing drugs
- Uncontrolled severe illness or medical condition (including uncontrolled diabetes mellitus)
- Concurrent or planned treatment with strong inhibitors or strong inducers of cytochrome P450 3A4/5 (a one week wash-out period is necessary for patients who are already on these treatments) (see Annex 1 and Annex 2)
- Concomitant vaccination with yellow fever vaccine
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Azienda Ospedaliera Spedali Civili di Brescia
Brescia, 25123
About this study
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
Adrenocortical cancer (ACC) is a rare aggressive tumor. The treatment of metastatic ACC is challenging and the current available treatments are mitotane, chemotherapy or the combination of both. Prognosis in locally advanced inoperable and metastatic ACC patients still remains poor, the 5-year overall survival being <15%. New treatment strategies are therefore needed. The taxanes are a class of drugs targeting the microtubules that have shown to be effective in the treatment of several malignancies but have not been fully developed in patients with ACC. Cabazitaxel is a new taxoid which promotes the tubulin assembly in vitro and stabilizes microtubules against cold-induced depolymerization as efficiently as docetaxel. Cabazitaxel was selected for development based on a better antiproliferative activity on resistant cell lines than docetaxel. The activity of the drug against several malignancies is currently tested in ongoing prospective studies, but to our knowledge neither preclinical nor clinical studies are currently testing cabaztaxel in ACC. This study is aimed to demonstrate that cabazitaxel is active in ACC, but the drug was never tested before in this clinical setting. A prospective, non-randomized, multicentre, open label, single arm, phase II study will be conducted in patients with advanced ACC. The phase II study will be conducted in 2 different Italian Institutions that are reference centers for ACC.
Read the detailed description
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.
- Conditions
- Adrenocortical Carcinoma
- Being tested
- Cabazitaxel
- Keywords
- Adrenocortical Carcinoma, Cabazitaxel
- Medical subject headings
- Adrenocortical Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CabazitaxelDrug
Cabazitaxel will be administered every 21 days
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | patients with advanced Adrenocortical- Carcinoma progressing after previous chemotherapy lines will be treated with Cabazitaxel Receives: Drug: Cabazitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess the clinical benefit after 4 months of the cabazitaxel in patients with locally advanced or metastatic ACC who progressed after cytotoxic therapy.
CT scan evaluated according to RECIST 1.1 criteria
Measured: 4 months
Secondary outcomes (5)
Assessment of Objective Response Rates (ORR)
ORR evaluated by RECIST criteria
Measured: Every cycle (21 days) for a maximum of 6 cycles and for 6 months follow up. Total 1 year
Assessment of overall survival
defined as the time from the date of the study start to date of death due to any cause
Measured: Every cycle (21 days) for a maximum of 6 cycles and for 6 months follow up. Total 1 year
Assessment of quality of life
EORTC quality of life questionnaire (QLQ)-C30 will be administered to patients
Measured: Every cycle (21 days) for a maximum of 6 cycles and for 6 months follow up. Total 1 year
Assessment of toxicity
evaluated by NCI CTCAE V4.03 criteria
Measured: Every cycle (21 days) for a maximum of 6 cycles and for 6 months follow up. Total 1 year
Assessment of hormone response
Evaluation of adrenocorticotropic hormone (ACTH), Testosterone, Progesterone, Cortisol, (Deidroepiandrosterone) DHEA-S, 17-hydroxide- progesterone, Androstenedione in serum. Evaluation of 24 hours urinary cortisol.
Measured: Every cycle (21 days) for a maximum of 6 cycles and for 6 months follow up. Total 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2017
- Study start25 Jan 2018
- Primary completion24 Jan 2021 (estimated)
- Study completion24 Jan 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for Adrenocortical CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- 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)
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
- Sponsor type
- University, hospital or other
- Collaborators
- San Luigi Gonzaga Hospital
- Responsible party
- Principal investigator, Alfredo Berruti, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
- Investigators
- Alfredo Berruti, MD, Principal investigator, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03257891
- Sponsor's protocol ID
- NP2729
- Acronym
- CabACC
- Status last verified
- Apr 2018
- First submitted
- 17 Aug 2017
- Last updated
- 11 Apr 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Berruti A, Ferrero A, Sperone P, Daffara F, Reimondo G, Papotti M, Dogliotti L, Angeli A, Terzolo M. Emerging drugs for adrenocortical carcinoma. Expert Opin Emerg Drugs. 2008 Sep;13(3):497-509. doi: 10.1517/14728214.13.3.497.
PubMed 18764725Fassnacht M, Terzolo M, Allolio B, Baudin E, Haak H, Berruti A, Welin S, Schade-Brittinger C, Lacroix A, Jarzab B, Sorbye H, Torpy DJ, Stepan V, Schteingart DE, Arlt W, Kroiss M, Leboulleux S, Sperone P, Sundin A, Hermsen I, Hahner S, Willenberg HS, Tabarin A, Quinkler M, de la Fouchardiere C, Schlumberger M, Mantero F, Weismann D, Beuschlein F, Gelderblom H, Wilmink H, Sender M, Edgerly M, Kenn W, Fojo T, Muller HH, Skogseid B; FIRM-ACT Study Group. Combination chemotherapy in advanced adrenocortical carcinoma. N Engl J Med. 2012 Jun 7;366(23):2189-97. doi: 10.1056/NEJMoa1200966. Epub 2012 May 2.
PubMed 22551107Bates SE, Shieh CY, Mickley LA, Dichek HL, Gazdar A, Loriaux DL, Fojo AT. Mitotane enhances cytotoxicity of chemotherapy in cell lines expressing a multidrug resistance gene (mdr-1/P-glycoprotein) which is also expressed by adrenocortical carcinomas. J Clin Endocrinol Metab. 1991 Jul;73(1):18-29. doi: 10.1210/jcem-73-1-18.
PubMed 1675220Chen KG, Sikic BI. Molecular pathways: regulation and therapeutic implications of multidrug resistance. Clin Cancer Res. 2012 Apr 1;18(7):1863-9. doi: 10.1158/1078-0432.CCR-11-1590. Epub 2012 Feb 16.
PubMed 22344233Berruti A, Sperone P, Ferrero A, Germano A, Ardito A, Priola AM, De Francia S, Volante M, Daffara F, Generali D, Leboulleux S, Perotti P, Baudin E, Papotti M, Terzolo M. Phase II study of weekly paclitaxel and sorafenib as second/third-line therapy in patients with adrenocortical carcinoma. Eur J Endocrinol. 2012 Mar;166(3):451-8. doi: 10.1530/EJE-11-0918. Epub 2011 Dec 21.
PubMed 22189997Gradishar WJ, Tjulandin S, Davidson N, Shaw H, Desai N, Bhar P, Hawkins M, O'Shaughnessy J. Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. J Clin Oncol. 2005 Nov 1;23(31):7794-803. doi: 10.1200/JCO.2005.04.937. Epub 2005 Sep 19.
PubMed 16172456Demeure MJ, Stephan E, Sinari S, Mount D, Gately S, Gonzales P, Hostetter G, Komorowski R, Kiefer J, Grant CS, Han H, Von Hoff DD, Bussey KJ. Preclinical investigation of nanoparticle albumin-bound paclitaxel as a potential treatment for adrenocortical cancer. Ann Surg. 2012 Jan;255(1):140-6. doi: 10.1097/SLA.0b013e3182402d21.
PubMed 22156929Mita AC, Figlin R, Mita MM. Cabazitaxel: more than a new taxane for metastatic castrate-resistant prostate cancer? Clin Cancer Res. 2012 Dec 15;18(24):6574-9. doi: 10.1158/1078-0432.CCR-12-1584. Epub 2012 Oct 22.
PubMed 23091116Montoya M, Brown JW, Fishman LM. Comparative effects of chemotherapeutic agents on the growth and survival of human adrenal carcinoma cells in culture. Horm Metab Res. 2008 May;40(5):302-5. doi: 10.1055/s-2008-1073139.
PubMed 18491247Kroiss M, Quinkler M, Lutz WK, Allolio B, Fassnacht M. Drug interactions with mitotane by induction of CYP3A4 metabolism in the clinical management of adrenocortical carcinoma. Clin Endocrinol (Oxf). 2011 Nov;75(5):585-91. doi: 10.1111/j.1365-2265.2011.04214.x.
PubMed 21883349Hasegawa E, Nakagawa S, Sato M, Tachikawa E, Yamato S. Effect of polyphenols on production of steroid hormones from human adrenocortical NCI-H295R cells. Biol Pharm Bull. 2013;36(2):228-37. doi: 10.1248/bpb.b12-00627.
PubMed 23370353Arrighi N, Bodei S, Lucente A, Michel MC, Zani D, Simeone C, Cunico SC, Spano P, Sigala S. Muscarinic receptors stimulate cell proliferation in the human urothelium-derived cell line UROtsa. Pharmacol Res. 2011 Oct;64(4):420-5. doi: 10.1016/j.phrs.2011.06.009. Epub 2011 Jun 28.
PubMed 21718784Simon R. Optimal two-stage designs for phase II clinical trials. Control Clin Trials. 1989 Mar;10(1):1-10. doi: 10.1016/0197-2456(89)90015-9.
PubMed 2702835Berruti A, Terzolo M, Sperone P, Pia A, Della Casa S, Gross DJ, Carnaghi C, Casali P, Porpiglia F, Mantero F, Reimondo G, Angeli A, Dogliotti L. Etoposide, doxorubicin and cisplatin plus mitotane in the treatment of advanced adrenocortical carcinoma: a large prospective phase II trial. Endocr Relat Cancer. 2005 Sep;12(3):657-66. doi: 10.1677/erc.1.01025.
PubMed 16172198Lagana M, Grisanti S, Ambrosini R, Cosentini D, Abate A, Zamparini M, Ferrari VD, Gianoncelli A, Turla A, Canu L, Terzolo M, Tiberio GAM, Sigala S, Berruti A. Phase II study of cabazitaxel as second-third line treatment in patients with metastatic adrenocortical carcinoma. ESMO Open. 2022 Apr;7(2):100422. doi: 10.1016/j.esmoop.2022.100422. Epub 2022 Mar 7.
PubMed 35272132
Study at a glance
From the registry record, last updated by the sponsor on 11 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03257891
- Acronym / sponsor ID
- CabACC / NP2729
- Conditions
- Adrenocortical Carcinoma
- Keywords
- Adrenocortical Carcinoma, Cabazitaxel
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- Azienda Socio Sanitaria Territoriale degli Spedali Civili di BresciaUniversity, hospital or other
- Collaborators
- San Luigi Gonzaga Hospital
- Study start
- 25 Jan 2018 (actual)
- Primary completion
- 24 Jan 2021 (estimated)
- Study completion
- 24 Jan 2022 (estimated)
- First posted
- 22 Aug 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Adrenocortical cancer (ACC) is a rare aggressive tumor. The treatment of metastatic ACC is challenging and the current available treatments are mitotane, chemotherapy or the combination of both. Prognosis in locally advanced inoperable and metastatic ACC patients still remains poor, the 5-year overall survival being <15%. New treatment strategies are therefore needed. The taxanes are a class of drugs targeting the microtubules that have shown to be effective in the treatment of several malignancies but have not been fully developed in patients with ACC. Cabazitaxel is a new taxoid which promotes the tubulin assembly in vitro and stabilizes microtubules against cold-induced depolymerization as efficiently as docetaxel. Cabazitaxel was selected for development based on a better antiproliferative activity on resistant cell lines than docetaxel. The activity of the drug against several malignancies is currently tested in ongoing prospective studies, but to our knowledge neither preclinical nor clinical studies are currently testing cabaztaxel in ACC. This study is aimed to demonstrate that cabazitaxel is active in ACC, but the drug was never tested before in this clinical setting. A prospective, non-randomized, multicentre, open label, single arm, phase II study will be conducted in patients with advanced ACC. The phase II study will be conducted in 2 different Italian Institutions that are reference centers for ACC.
Detailed description
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- 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
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: Cabazitaxelpatients with advanced Adrenocortical- Carcinoma progressing after previous chemotherapy lines will be treated with Cabazitaxel |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Histologically confirmed diagnosis of ACC
- Locally advanced or metastatic disease not amenable to radical surgery resection
- Radiologically monitorised disease
- Progressing disease after one to three cytotoxic chemotherapy regimes (including a platin-based protocol)
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Key exclusion criteria (11 listed)
- History of prior malignancy, except for cured non-melanoma skin cancer, cured in situ cervical carcinoma, or other treated malignancies with no evidence of disease for at least three years.
- Serum creatinine > 1.5 x ULN or hepatic insufficiency, Hemoglobin <10.0 g/dL;
- Total bilirubin >1x ULN, Creatinine < 1.5 ULN;
- Decompensated heart failure (ejection fraction <45%), myocardial infarction or revascularization procedure during the last 6 months, unstable angina pectoris, uncontrolled cardiac arrhythmia
- Pregnancy or breast feeding
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CabazitaxelCabazitaxel will be administered every 21 days | Drug | Arm 1 |
Primary outcome
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
5 secondary outcomes
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
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
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
Assessment of toxicity
Time frame: Every cycle (21 days) for a maximum of 6 cycles and for 6 months follow up. Total 1 year
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Apr 2018.
- Results publication: PubMed 18764725Berruti A, Ferrero A, Sperone P, Daffara F, Reimondo G, Papotti M, Dogliotti L, Angeli A, Terzolo M. Emerging drugs for adrenocortical carcinoma. Expert Opin Emerg Drugs. 2008 Sep;13(3):497-509. doi: 10.1517/14728214.13.3.497.
- Results publication: PubMed 22551107Fassnacht M, Terzolo M, Allolio B, Baudin E, Haak H, Berruti A, Welin S, Schade-Brittinger C, Lacroix A, Jarzab B, Sorbye H, Torpy DJ, Stepan V, Schteingart DE, Arlt W, Kroiss M, Leboulleux S, Sperone P, Sundin A, Hermsen I, Hahner S, Willenberg HS, Tabarin A, Quinkler M, de la Fouchardiere C, Schlumberger M, Mantero F, Weismann D, Beuschlein F, Gelderblom H, Wilmink H, Sender M, Edgerly M, Kenn W, Fojo T, Muller HH, Skogseid B; FIRM-ACT Study Group. Combination chemotherapy in advanced adrenocortical carcinoma. N Engl J Med. 2012 Jun 7;366(23):2189-97. doi: 10.1056/NEJMoa1200966. Epub 2012 May 2.
- Results publication: PubMed 1675220Bates SE, Shieh CY, Mickley LA, Dichek HL, Gazdar A, Loriaux DL, Fojo AT. Mitotane enhances cytotoxicity of chemotherapy in cell lines expressing a multidrug resistance gene (mdr-1/P-glycoprotein) which is also expressed by adrenocortical carcinomas. J Clin Endocrinol Metab. 1991 Jul;73(1):18-29. doi: 10.1210/jcem-73-1-18.
- Results publication: PubMed 22344233Chen KG, Sikic BI. Molecular pathways: regulation and therapeutic implications of multidrug resistance. Clin Cancer Res. 2012 Apr 1;18(7):1863-9. doi: 10.1158/1078-0432.CCR-11-1590. Epub 2012 Feb 16.
- Results publication: PubMed 22189997Berruti A, Sperone P, Ferrero A, Germano A, Ardito A, Priola AM, De Francia S, Volante M, Daffara F, Generali D, Leboulleux S, Perotti P, Baudin E, Papotti M, Terzolo M. Phase II study of weekly paclitaxel and sorafenib as second/third-line therapy in patients with adrenocortical carcinoma. Eur J Endocrinol. 2012 Mar;166(3):451-8. doi: 10.1530/EJE-11-0918. Epub 2011 Dec 21.
- Results publication: PubMed 16172456Gradishar WJ, Tjulandin S, Davidson N, Shaw H, Desai N, Bhar P, Hawkins M, O'Shaughnessy J. Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. J Clin Oncol. 2005 Nov 1;23(31):7794-803. doi: 10.1200/JCO.2005.04.937. Epub 2005 Sep 19.
- Results publication: PubMed 22156929Demeure MJ, Stephan E, Sinari S, Mount D, Gately S, Gonzales P, Hostetter G, Komorowski R, Kiefer J, Grant CS, Han H, Von Hoff DD, Bussey KJ. Preclinical investigation of nanoparticle albumin-bound paclitaxel as a potential treatment for adrenocortical cancer. Ann Surg. 2012 Jan;255(1):140-6. doi: 10.1097/SLA.0b013e3182402d21.
- Results publication: PubMed 23091116Mita AC, Figlin R, Mita MM. Cabazitaxel: more than a new taxane for metastatic castrate-resistant prostate cancer? Clin Cancer Res. 2012 Dec 15;18(24):6574-9. doi: 10.1158/1078-0432.CCR-12-1584. Epub 2012 Oct 22.
- Results publication: PubMed 18491247Montoya M, Brown JW, Fishman LM. Comparative effects of chemotherapeutic agents on the growth and survival of human adrenal carcinoma cells in culture. Horm Metab Res. 2008 May;40(5):302-5. doi: 10.1055/s-2008-1073139.
- Results publication: PubMed 21883349Kroiss M, Quinkler M, Lutz WK, Allolio B, Fassnacht M. Drug interactions with mitotane by induction of CYP3A4 metabolism in the clinical management of adrenocortical carcinoma. Clin Endocrinol (Oxf). 2011 Nov;75(5):585-91. doi: 10.1111/j.1365-2265.2011.04214.x.
- Results publication: PubMed 23370353Hasegawa E, Nakagawa S, Sato M, Tachikawa E, Yamato S. Effect of polyphenols on production of steroid hormones from human adrenocortical NCI-H295R cells. Biol Pharm Bull. 2013;36(2):228-37. doi: 10.1248/bpb.b12-00627.
- Results publication: PubMed 21718784Arrighi N, Bodei S, Lucente A, Michel MC, Zani D, Simeone C, Cunico SC, Spano P, Sigala S. Muscarinic receptors stimulate cell proliferation in the human urothelium-derived cell line UROtsa. Pharmacol Res. 2011 Oct;64(4):420-5. doi: 10.1016/j.phrs.2011.06.009. Epub 2011 Jun 28.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alfredo Berruti, MD principal investigator
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cabazitaxel in people with Adrenocortical Carcinoma, run by Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 11 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Alfredo Berruti, MD (030399 ext. 5410, alfredo.berruti@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03257891, which also lists 15 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Apr 2018.