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.

Condition	Treatment or Intervention	Phase
Carcinoma, Adrenal Cortical	Drug: Etoposide  Drug: Doxorubicin  Drug: Cisplatin  Drug: Streptozotocin  Drug: Mitotane	Phase III

Further Study Details: 

Primary Outcomes: Overall survival
Secondary Outcomes: 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
Expected Total Enrollment:  300

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  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

Britt Skogseid, MD      +46 18 611 00 00    Britt.skogseid@medsci.uu.se
Martin Fassnacht, MD      +49-931-201-0  Ext. 36788    Fassnacht@medizin.uni-wuerzburg.de

Australia
      Royal Adelaide Hospital, Adelaide,  SA 5000,  Australia; Recruiting
France
      Institut Gustave Roussy, Villejuif,  94805,  France; Not yet recruiting
Germany
      University of Wuerzburg - Dept. of Medicine, Wuerzburg,  97080,  Germany; Recruiting
      University of Duesseldorf, Dept. of Endocrrinology, Duesseldorf,  40001,  Germany; Recruiting
      University of Munich, Dept. of Internal Medicine (Innenstadt), Munich,  80336,  Germany; Recruiting
      Otto-von-Guericke University; Dept. of Endocrinology, Magdeburg,  39120,  Germany; Recruiting
      Charité-University, Dept. of Endocrinology, Berlin,  Germany; Recruiting
Italy
      University of Turin, Dept of Internal Medicine, Orbassano,  10043,  Italy; Recruiting
Netherlands
      Maxima Medisch Centrum; Dept. of Internal Medicine, Eindhoven,  5631 BM,  Netherlands; Recruiting
      Academisch Medisch Centrum; Dept. of Endocrinology, Amsterdam,  1105 AZ,  Netherlands; Recruiting
      Leiden University Medical Center, Leiden,  Netherlands; Not yet recruiting
      University Hospital Groningen; Dept. of Internal Medine, Groningen,  9700,  Netherlands; Not yet recruiting
      Vrije Universiteit Medisch Centrum, Amsterdam,  1007,  Netherlands; Not yet recruiting
Sweden
      Uppsala University Hospital - Dept of Medical Sciences, Uppsala,  751 85,  Sweden; Recruiting
      Department of Medicine, The Jubileum Institute, Lund University, Lund,  Sweden; Recruiting
      Department of Oncology, Sahlgrenska University Hospital, GOTHENBURG,  Sweden; Recruiting
      Department of Oncology, Linköping University Hospital, Linköping,  Sweden; Recruiting
      Dept of Surgery, Karolinska Hospital, Stockholm, Stockholm,  Sweden; Not yet recruiting

Study chairs or principal investigators

Britt Skogseid, MD,  Study Chair,  Uppsala University Hospital   

Study ID Numbers:  CO-ACT-001
Record last reviewed:  December 2004
Last Updated:  December 20, 2004
Record first received:  October 19, 2004
ClinicalTrials.gov Identifier:  NCT00094497
Health Authority: Germany: Federal Institute for Drugs and Medicinal Devices (Awaiting confirmation); Sweden: Medical Products Agency (Awaiting confirmation); France: Afssaps - French Health Products Safety Agency (Awaiting confirmation); Italy: Ministry of Health (Awaiting confirmation); Netherlands: Independent Ethics Committee (Awaiting confirmation); Australia: Department of Health and Ageing Therapeutic Goods Administration (Awaiting confirmation)
ClinicalTrials.gov processed this record on 2005-04-08