Trial in Locally Advanced and Metastatic Adrenocortical Carcinoma Treatment (FIRM-ACT)
Information source: Collaborative Group for Adrenocortical Carcinoma Treatment
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Carcinoma, Adrenal Cortical
Intervention: Etoposide (Drug); Doxorubicin (Drug); Cisplatin (Drug); Streptozotocin (Drug); Mitotane (Drug)
Phase: Phase 3
Status: Completed
Sponsored by: Collaborative Group for Adrenocortical Carcinoma Treatment Official(s) and/or principal investigator(s): Britt Skogseid, MD, Study Chair, Affiliation: Uppsala University Hospital Martin Fassnacht, MD, Principal Investigator, Affiliation: University of Würzburg
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.
Clinical Details
Official title: First International Randomized Trial in Locally Advanced and Metastatic Adrenocortical Carcinoma Treatment
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Overall survival
Secondary outcome: Time to progression (TTP)Quality of life as measured by QLQ-C30 Best overall response rate and duration of response Number of disease-free patients Impact of reaching mitotane blood levels between 14-20 mg/l in both arms on survival and overall response rate TTP of both regimens as second line treatment in case of failure of the other initial regime Pharmakinetics of mitotane (substudy)
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.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
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
Locations and Contacts
Royal Adelaide Hospital, Adelaide SA 5000, Australia
University of Graz, Graz 8036, Austria
Clinique Marc Linquette, Lille, France
Centre Leon Berard, Lyon, France
Hospital de Marseille la timone, Marseille 13385, France
Cochin Hospital, Paris 75679, France
Hospital Bordeaux haut leveque, Pessac 33600, France
Institut Gustave Roussy, Villejuif 94805, France
Charité-University, Dept. of Endocrinology; Campus Benjamin Franklin, Berlin, Germany
Charité-Universitätsmedizin Berlin - Campus Mitte, Berlin, Germany
Dept. of Medicine III, Dresden, Germany
University of Duesseldorf, Dept. of Endocrrinology, Duesseldorf 40001, Germany
Zentrum für Innere Medizin - Endokrinologie des Universitätsklinikum Essen, Essen, Germany
Endokrinologie Medizinische Hochschule Hannover, Hannover, Germany
Otto-von-Guericke University; Dept. of Endocrinology, Magdeburg 39120, Germany
Dept of Medicine I, Mainz, Germany
University of Munich, Dept. of Internal Medicine (Innenstadt), Munich 80336, Germany
University of Wuerzburg - Dept. of Medicine, Wuerzburg 97080, Germany
University of Turin, Dept of Internal Medicine, Orbassano 10043, Italy
Clinica Endocrinologica, Università di Padova, Azienda Ospedaliera di Padova, Padova, Italy
Academisch Medisch Centrum; Dept. of Endocrinology, Amsterdam 1105 AZ, Netherlands
Vrije Universiteit Medisch Centrum, Amsterdam 1007, Netherlands
Maxima Medisch Centrum; Dept. of Internal Medicine, Eindhoven 5631 BM, Netherlands
University Hospital Groningen; Dept. of Internal Medine, Groningen 9700, Netherlands
Leiden University Medical Center, Leiden, Netherlands
Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden
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 751 85, Sweden
National Cancer Institute - Center for Cancer Research, Bethesda, Maryland, United States
University of Michigan, Department of Internal Medicine, Ann Arbor, Michigan 48109, United States
Additional Information
Click here for more information about this study: First International Randomized trial in locally advanced and Metastatic Adrenocortical Carcinoma Treatment (FIRM-ACT)
Starting date: June 2004
Last updated: May 14, 2012
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