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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

Page last updated: August 23, 2015

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