Trial in Locally Advanced and Metastatic Adrenocortical Carcinoma Treatment (FIRM-ACT)

NCT00094497 | Completed Phase 3 Results DMC

• 1 other identifier: CO-ACT-001
• Study Type: interventional
• Target: 304
• Locations: 7 countries
• Sites: 31

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.

Conditions

Carcinoma, Adrenal Cortical

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  participants who died among those randomized to first-line therapy

  every 8 weeks until death up to 5 years

Secondary Outcomes (4)

• Progression-free Survival

  every 8 weeks until progression or death up to 5 years

• Change in Quality of Life as Measured by QLQ-C30

  baseline and 8 weeks

• Best Overall Response Rate

  every 8 weeks up to 5 years

• Number of Disease-free Patients

  every 8 weeks until progression (up to 5 years)

Other Outcomes (3)

• TTP of Both Regimens as Second Line Treatment in Case of Failure of the Other Initial Regime

  every 8 weeks until progression or until Dec 2010

• Pharmakinetics of Mitotane (Substudy)

  11 time points in the first 12 weeks

• Impact of Reaching Mitotane Blood Levels Between 14-20 mg/l in Both Arms on Survival and Overall Response Rate

  every 8 weeks until progression or until Dec 2010

Study Arms (2)

EDP-M

ACTIVE COMPARATOR

etopodide, doxorubicin, cisplatin and mitotane

Drug: Etoposide; Drug: Doxorubicin; Drug: Cisplatin; Drug: Mitotane

Sz-M

ACTIVE COMPARATOR

streptozotocin and mitotane

Drug: Streptozotocin; Drug: Mitotane

Interventions

Etoposide DRUG

EDP-M

Doxorubicin DRUG

EDP-M

Cisplatin DRUG

EDP-M

Streptozotocin DRUG

Sz-M

Mitotane DRUG

EDP-M; Sz-M

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Collaborative Group for Adrenocortical Carcinoma Treatment: lead
• German Federal Ministry of Education and Research: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (32)

National Cancer Institute - Center for Cancer Research

Bethesda, Maryland, United States

Location

University of Michigan, Department of Internal Medicine

Ann Arbor, Michigan, 48109, United States

Location

Royal Adelaide Hospital

Adelaide, SA 5000, Australia

Location

University of Graz

Graz, 8036, Austria

Location

Clinique Marc Linquette

Lille, France

Location

Centre Leon Berard

Lyon, France

Location

Hospital de Marseille la timone

Marseille, 13385, France

Location

Cochin Hospital

Paris, 75679, France

Location

Hospital Bordeaux haut leveque

Pessac, 33600, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Charité-University, Dept. of Endocrinology; Campus Benjamin Franklin

Berlin, Germany

Location

Charité-Universitätsmedizin Berlin - Campus Mitte

Berlin, Germany

Location

Dept. of Medicine III

Dresden, Germany

Location

University of Duesseldorf, Dept. of Endocrrinology

Düsseldorf, 40001, Germany

Location

Zentrum für Innere Medizin - Endokrinologie des Universitätsklinikum Essen

Essen, Germany

Location

Endokrinologie Medizinische Hochschule Hannover

Hanover, Germany

Location

Otto-von-Guericke University; Dept. of Endocrinology

Magdeburg, 39120, Germany

Location

Dept of Medicine I

Mainz, Germany

Location

University of Munich, Dept. of Internal Medicine (Innenstadt)

Munich, 80336, Germany

Location

University of Wuerzburg - Dept. of Medicine

Würzburg, 97080, Germany

Location

University of Turin, Dept of Internal Medicine

Orbassano, 10043, Italy

Location

Clinica Endocrinologica, Università di Padova, Azienda Ospedaliera di Padova

Padua, Italy

Location

Vrije Universiteit Medisch Centrum

Amsterdam, 1007, Netherlands

Location

Academisch Medisch Centrum; Dept. of Endocrinology

Amsterdam, 1105 AZ, Netherlands

Location

Maxima Medisch Centrum; Dept. of Internal Medicine

Eindhoven, 5631 BM, Netherlands

Location

University Hospital Groningen; Dept. of Internal Medine

Groningen, 9700, Netherlands

Location

Leiden University Medical Center

Leiden, Netherlands

Location

Department of Oncology, Sahlgrenska University Hospital

Gothenburg, Sweden

Location

Department of Oncology, Linköping University Hospital

Linköping, Sweden

Location

Department of Medicine, The Jubileum Institute, Lund University

Lund, Sweden

Location

Dept of Surgery, Karolinska Hospital, Stockholm

Stockholm, Sweden

Location

Uppsala University Hospital - Dept of Medical Sciences

Uppsala, 751 85, Sweden

Location

Related Publications (1)

• Fassnacht M, Terzolo M, Allolio B, Baudin E, Haak H, Berruti A, Welin S, Schade-Brittinger C, Lacroix A, Jarzab B, Sorbye H, Torpy DJ, Stepan V, Schteingart DE, Arlt W, Kroiss M, Leboulleux S, Sperone P, Sundin A, Hermsen I, Hahner S, Willenberg HS, Tabarin A, Quinkler M, de la Fouchardiere C, Schlumberger M, Mantero F, Weismann D, Beuschlein F, Gelderblom H, Wilmink H, Sender M, Edgerly M, Kenn W, Fojo T, Muller HH, Skogseid B; FIRM-ACT Study Group. Combination chemotherapy in advanced adrenocortical carcinoma. N Engl J Med. 2012 Jun 7;366(23):2189-97. doi: 10.1056/NEJMoa1200966. Epub 2012 May 2.

  PMID: 22551107 RESULT

Related Links

• Click here for more information about this study: First International Randomized trial in locally advanced and Metastatic Adrenocortical Carcinoma Treatment (FIRM-ACT)

MeSH Terms

Conditions

Adrenocortical Carcinoma

Interventions

Etoposide; Doxorubicin; Cisplatin; Streptozocin; Mitotane

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adrenal Cortex Neoplasms; Adrenal Gland Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Adrenal Cortex Diseases; Adrenal Gland Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Daunorubicin; Anthracyclines; Naphthacenes; Aminoglycosides; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Nitrosourea Compounds; Urea; Amides; Nitroso Compounds; Hydrocarbons, Chlorinated; Hydrocarbons, Halogenated

Results Point of Contact

• Title: Martin Fassnacht
• Organization: University Hospital of Wuerzburg, Germany

fassnacht_m@ukw.de

+49-931-201-39021

Study Officials

• Britt Skogseid, MD

  Uppsala University Hospital

  STUDY CHAIR

• Martin Fassnacht, MD

  University of Würzburg

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Co-PI

Study Record Dates

• First Submitted: October 19, 2004
• First Posted: October 20, 2004
• Study Start: June 1, 2004
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2010
• Last Updated: September 21, 2016
• Results First Posted: September 21, 2016

Record last verified: 2016-09

Locations

DE (10); IT (2); US (2); FR (6); AU (1); SE (5); NL (5)