Trial in Locally Advanced and Metastatic Adrenocortical Carcinoma Treatment (FIRM-ACT)
- Conditions
- Carcinoma, Adrenal Cortical
- Interventions
- Registration Number
- NCT00094497
- Lead Sponsor
- Collaborative Group for Adrenocortical Carcinoma Treatment
- Brief Summary
The purpose of this study is to determine whether treatment with etoposide, doxorubicin, cisplatin and mitotane (EDP/M) prolongs survival as compared to streptozotocin and mitotane (Sz/M) in patients with advanced adrenocortical carcinoma (ACC) whose disease is not amenable to complete surgical resection.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 304
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Sz-M Streptozotocin streptozotocin and mitotane Sz-M Mitotane streptozotocin and mitotane EDP-M Etoposide etopodide, doxorubicin, cisplatin and mitotane EDP-M Doxorubicin etopodide, doxorubicin, cisplatin and mitotane EDP-M Cisplatin etopodide, doxorubicin, cisplatin and mitotane EDP-M Mitotane etopodide, doxorubicin, cisplatin and mitotane
- Primary Outcome Measures
Name Time Method Overall Survival every 8 weeks until death up to 5 years participants who died among those randomized to first-line therapy
- Secondary Outcome Measures
Name Time Method Best Overall Response Rate every 8 weeks up to 5 years RECIST 1.0 was used to evaluate response
Number of Disease-free Patients every 8 weeks until progression (up to 5 years) complete response or disease-free by time of surgery
Change in Quality of Life as Measured by QLQ-C30 baseline and 8 weeks scale ranged from 0 to 100 with higher score meaning greater quality of life
Progression-free Survival every 8 weeks until progression or death up to 5 years
Trial Locations
- Locations (32)
National Cancer Institute - Center for Cancer Research
🇺🇸Bethesda, Maryland, United States
University of Michigan, Department of Internal Medicine
🇺🇸Ann Arbor, Michigan, United States
Royal Adelaide Hospital
🇦🇺Adelaide, Australia
University of Graz
🇦🇹Graz, Austria
Institut Gustave Roussy
🇫🇷Villejuif, France
Hospital Bordeaux haut leveque
🇫🇷Pessac, France
Endokrinologie Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Charité-Universitätsmedizin Berlin - Campus Mitte
🇩🇪Berlin, Germany
Dept. of Medicine III
🇩🇪Dresden, Germany
Dept of Medicine I
🇩🇪Mainz, Germany
University of Duesseldorf, Dept. of Endocrrinology
🇩🇪Duesseldorf, Germany
University of Wuerzburg - Dept. of Medicine
🇩🇪Wuerzburg, Germany
Academisch Medisch Centrum; Dept. of Endocrinology
🇳🇱Amsterdam, Netherlands
Maxima Medisch Centrum; Dept. of Internal Medicine
🇳🇱Eindhoven, Netherlands
University of Turin, Dept of Internal Medicine
🇮🇹Orbassano, Italy
Clinica Endocrinologica, Università di Padova, Azienda Ospedaliera di Padova
🇮🇹Padova, Italy
Vrije Universiteit Medisch Centrum
🇳🇱Amsterdam, Netherlands
Department of Oncology, Sahlgrenska University Hospital
🇸🇪Gothenburg, Sweden
University Hospital Groningen; Dept. of Internal Medine
🇳🇱Groningen, Netherlands
Leiden University Medical Center
🇳🇱Leiden, Netherlands
Department of Oncology, Linköping University Hospital
🇸🇪Linköping, Sweden
Department of Medicine, The Jubileum Institute, Lund University
🇸🇪Lund, Sweden
Dept of Surgery, Karolinska Hospital, Stockholm
🇸🇪Stockholm, Sweden
Uppsala University Hospital - Dept of Medical Sciences
🇸🇪Uppsala, Sweden
Clinique Marc Linquette
🇫🇷Lille, France
Centre Leon Berard
🇫🇷Lyon, France
Cochin Hospital
🇫🇷Paris, France
Hospital de Marseille la timone
🇫🇷Marseille, France
Zentrum für Innere Medizin - Endokrinologie des Universitätsklinikum Essen
🇩🇪Essen, Germany
University of Munich, Dept. of Internal Medicine (Innenstadt)
🇩🇪Munich, Germany
Otto-von-Guericke University; Dept. of Endocrinology
🇩🇪Magdeburg, Germany
Charité-University, Dept. of Endocrinology; Campus Benjamin Franklin
🇩🇪Berlin, Germany