- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00094497
Trial in Locally Advanced and Metastatic Adrenocortical Carcinoma Treatment (FIRM-ACT)
First International Randomized Trial in Locally Advanced and Metastatic Adrenocortical Carcinoma Treatment
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The Firm-ACT trial is the first ever conducted randomized controlled phase III trial in adrenocortical carcinoma (ACC), a rare malignancy with poor prognosis. It will provide results leading to the establishment of an urgently needed gold standard chemotherapy regimen for patients with locally advanced or metastatic ACC. To this end the trial compares the two most promising drug combinations investigated in phase II trials, considered by the "International Consensus Conference on Adrenal Cancer" (Ann Arbor/USA, 2003) as valuable first line treatments for advanced ACC. The first regimen consists of etoposide, doxorubicin, cisplatin plus mitotane (EDP-M), the second regiment employs streptozotocin plus mitotane (Sz-M). Over a period of five years this international trial will include 300 patients with advanced ACC from different European countries. Blood mitotane concentrations will be monitored, aiming at drug levels between 14 - 20 mg/L. Patients not responding to the first line treatment will be switched to the alternative regimen. The primary objective of this trial is to investigate whether EDP-M given as first line treatment will prolong survival as compared to Sz-M. Secondary endpoints are quality of life, time to progression, best overall response rate and duration of response. In addition, the trial evaluates the role of reaching therapeutic mitotane serum concentrations for survival and tumour response and assesses the value of the two alternative treatment regimens as second line therapy in advanced ACC. Moreover, the FIRM-ACT trial will generate a lasting structural basis for successful future trials in ACC.
In a substudy of 40 patients a detailed analysis of the pharmacokinetics of oral mitotane will be analysed. Two different mitotane treatment regimens ("low dose" vs. "high dose") will be compared.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Adelaide, Australia, SA 5000
- Royal Adelaide Hospital
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Graz, Austria, 8036
- University of Graz
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Lille, France
- Clinique Marc Linquette
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Lyon, France
- Centre Léon Berard
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Marseille, France, 13385
- Hospital de Marseille la timone
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Paris, France, 75679
- Cochin Hospital
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Pessac, France, 33600
- Hospital Bordeaux haut leveque
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Villejuif, France, 94805
- Institut Gustave Roussy
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Berlin, Germany
- Charité-University, Dept. of Endocrinology; Campus Benjamin Franklin
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Berlin, Germany
- Charité-Universitätsmedizin Berlin - Campus Mitte
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Dresden, Germany
- Dept. of Medicine III
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Duesseldorf, Germany, 40001
- University of Duesseldorf, Dept. of Endocrrinology
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Essen, Germany
- Zentrum für Innere Medizin - Endokrinologie des Universitätsklinikum Essen
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Hannover, Germany
- Endokrinologie Medizinische Hochschule Hannover
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Magdeburg, Germany, 39120
- Otto-von-Guericke University; Dept. of Endocrinology
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Mainz, Germany
- Dept of Medicine I
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Munich, Germany, 80336
- University of Munich, Dept. of Internal Medicine (Innenstadt)
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Wuerzburg, Germany, 97080
- University of Wuerzburg - Dept. of Medicine
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Orbassano, Italy, 10043
- University of Turin, Dept of Internal Medicine
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Padova, Italy
- Clinica Endocrinologica, Università di Padova, Azienda Ospedaliera di Padova
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Amsterdam, Netherlands, 1007
- Vrije Universiteit Medisch Centrum
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Amsterdam, Netherlands, 1105 AZ
- Academisch Medisch Centrum; Dept. of Endocrinology
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Eindhoven, Netherlands, 5631 BM
- Maxima Medisch Centrum; Dept. of Internal Medicine
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Groningen, Netherlands, 9700
- University Hospital Groningen; Dept. of Internal Medine
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Leiden, Netherlands
- Leiden University Medical Center
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Gothenburg, Sweden
- Department of Oncology, Sahlgrenska University Hospital
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Linköping, Sweden
- Department of Oncology, Linköping University Hospital
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Lund, Sweden
- Department of Medicine, The Jubileum Institute, Lund University
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Stockholm, Sweden
- Dept of Surgery, Karolinska Hospital, Stockholm
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Uppsala, Sweden, 751 85
- Uppsala University Hospital - Dept of Medical Sciences
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Maryland
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Bethesda, Maryland, United States
- National Cancer Institute - Center for Cancer Research
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Michigan
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Ann Arbor, Michigan, United States, 48109
- University of Michigan, Department of Internal Medicine
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Histologically confirmed diagnosis of adrenocortical carcinoma
- Locally advanced or metastatic disease not amenable to radical surgery resection (Stage III-IV)
- Radiologically monitorable disease
- ECOG performance status 0-2
- Life expectancy > 3 months
- 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 (including availability for follow-up visits)
- Previous palliative surgery, radiotherapy or radiofrequency ablation is acceptable as long as radiologically monitorable disease is verifiable afterwards.
Exclusion Criteria:
- History of prior malignancy, except for cured non-melanoma skin cancer, curatively in situ cervical carcinoma, or other cancers treated with no evidence of disease for at least five years.
- Previous cytotoxic chemotherapy for adrenocortical carcinoma
- Renal insufficiency (serum creatinine ≥2 mg/dl or creatinine clearance ≤ 50 ml/min)
- Hepatic insufficiency (serum bilirubin ≥2 x the institutional upper limit of normal range and/or serum transaminases ≥ 3 x the institutional upper limit of normal range; exception: in patients on mitotane, transaminase levels up to 5 x the institutional upper limit of normal range are acceptable)
- Pregnancy or breast feeding
- Known hypersensitivity to any drug included in the treatment protocol
- Presence of active infection
- Any other severe clinical condition that in the judgment of the local investigator would place the patient at undue risk or interfere with the study completion
- Decompensated heart failure (ejection fraction <50%), myocardial infarction or revascularization procedure during the last 6 months, unstable angina pectoris, and uncontrolled cardiac arrhythmia
- Current treatment with other experimental drugs and/or previous participation in clinical trials with other experimental agents for adrenocortical carcinoma
- Prisoners
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Active Comparator: EDP-M
etopodide, doxorubicin, cisplatin and mitotane
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Active Comparator: Sz-M
streptozotocin and mitotane
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Overall Survival
Time Frame: every 8 weeks until death up to 5 years
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participants who died among those randomized to first-line therapy
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every 8 weeks until death up to 5 years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression-free Survival
Time Frame: every 8 weeks until progression or death up to 5 years
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every 8 weeks until progression or death up to 5 years
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Change in Quality of Life as Measured by QLQ-C30
Time Frame: baseline and 8 weeks
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scale ranged from 0 to 100 with higher score meaning greater quality of life
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baseline and 8 weeks
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Best Overall Response Rate
Time Frame: every 8 weeks up to 5 years
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RECIST 1.0 was used to evaluate response
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every 8 weeks up to 5 years
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Number of Disease-free Patients
Time Frame: every 8 weeks until progression (up to 5 years)
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complete response or disease-free by time of surgery
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every 8 weeks until progression (up to 5 years)
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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TTP of Both Regimens as Second Line Treatment in Case of Failure of the Other Initial Regime
Time Frame: every 8 weeks until progression or until Dec 2010
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every 8 weeks until progression or until Dec 2010
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Pharmakinetics of Mitotane (Substudy)
Time Frame: 11 time points in the first 12 weeks
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To study the relationship between mitotane dose (daily and cumulative) and mitotane plasma concentrations using one of two pre-defined treatment regimens (high-dose and low-dose).
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11 time points in the first 12 weeks
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Impact of Reaching Mitotane Blood Levels Between 14-20 mg/l in Both Arms on Survival and Overall Response Rate
Time Frame: every 8 weeks until progression or until Dec 2010
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every 8 weeks until progression or until Dec 2010
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Collaborators and Investigators
Investigators
- Study Chair: Britt Skogseid, MD, Uppsala University Hospital
- Principal Investigator: Martin Fassnacht, MD, University of Würzburg
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Adenocarcinoma
- Neoplasms, Glandular and Epithelial
- Endocrine System Diseases
- Endocrine Gland Neoplasms
- Adrenal Gland Diseases
- Adrenal Cortex Neoplasms
- Adrenal Gland Neoplasms
- Adrenal Cortex Diseases
- Carcinoma
- Adrenocortical Carcinoma
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Antineoplastic Agents, Hormonal
- Antineoplastic Agents, Phytogenic
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Antibiotics, Antineoplastic
- Etoposide
- Doxorubicin
- Mitotane
- Streptozocin
Other Study ID Numbers
- CO-ACT-001
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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