Trial in Locally Advanced and Metastatic Adrenocortical Carcinoma Treatment (FIRM-ACT)
Overview[ - collapse ][ - ]
| Purpose | 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 | Carcinoma, Adrenal Cortical |
| Intervention | Drug: Etoposide Drug: Doxorubicin Drug: Cisplatin Drug: Streptozotocin Drug: Mitotane |
| Phase | Phase 3 |
| Sponsor | Collaborative Group for Adrenocortical Carcinoma Treatment |
| Responsible Party | Collaborative Group for Adrenocortical Carcinoma Treatment |
| ClinicalTrials.gov Identifier | NCT00094497 |
| First Received | October 19, 2004 |
| Last Updated | May 14, 2012 |
| Last verified | May 2012 |
Tracking Information[ + expand ][ + ]
| First Received Date | October 19, 2004 |
|---|---|
| Last Updated Date | May 14, 2012 |
| Start Date | June 2004 |
| Estimated Primary Completion Date | December 2010 |
| Current Primary Outcome Measures | Overall survival [Time Frame: At the final analysis] [Designated as safety issue: No] |
| Current Secondary Outcome Measures |
|
Descriptive Information[ + expand ][ + ]
| Brief Title | Trial in Locally Advanced and Metastatic Adrenocortical Carcinoma Treatment (FIRM-ACT) |
|---|---|
| Official Title | First International Randomized Trial in Locally Advanced and Metastatic 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. |
| Study Type | Interventional |
| Study Phase | Phase 3 |
| Study Design | Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment |
| Condition | Carcinoma, Adrenal Cortical |
| Intervention | Drug: Etoposide Drug: Doxorubicin Drug: Cisplatin Drug: Streptozotocin Drug: Mitotane |
| Study Arm (s) | Not Provided |
Recruitment Information[ + expand ][ + ]
| Recruitment Status | Completed |
|---|---|
| Estimated Enrollment | 300 |
| Estimated Completion Date | December 2010 |
| Estimated Primary Completion Date | December 2010 |
| Eligibility 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 |
| Gender | Both |
| Ages | 18 Years |
| Accepts Healthy Volunteers | No |
| Contacts | Not Provided |
| Location Countries | United States, Australia, Austria, France, Germany, Italy, Netherlands, Sweden |
Administrative Information[ + expand ][ + ]
| NCT Number | NCT00094497 |
|---|---|
| Other Study ID Numbers | CO-ACT-001 |
| Has Data Monitoring Committee | Yes |
| Information Provided By | Collaborative Group for Adrenocortical Carcinoma Treatment |
| Study Sponsor | Collaborative Group for Adrenocortical Carcinoma Treatment |
| Collaborators | German Federal Ministry of Education and Research National Cancer Institute (NCI) |
| Investigators | Study Chair: Britt Skogseid, MD Uppsala University HospitalPrincipal Investigator: Martin Fassnacht, MD University of Würzburg |
| Verification Date | May 2012 |
Locations[ + expand ][ + ]
| National Cancer Institute - Center for Cancer Research | Bethesda, Maryland, United States |
|---|---|
| University of Michigan, Department of Internal Medicine | Ann Arbor, Michigan, United States, 48109 |
| Royal Adelaide Hospital | Adelaide, Australia, SA 5000 |
| University of Graz | Graz, Austria, 8036 |
| Clinique Marc Linquette | Lille, France |
| Centre Leon Berard | Lyon, France |
| Hospital de Marseille la timone | Marseille, France, 13385 |
| Cochin Hospital | Paris, France, 75679 |
| Hospital Bordeaux haut leveque | Pessac, France, 33600 |
| Institut Gustave Roussy | Villejuif, France, 94805 |
| 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, Germany, 40001 |
| Zentrum für Innere Medizin - Endokrinologie des Universitätsklinikum Essen | Essen, Germany |
| Endokrinologie Medizinische Hochschule Hannover | Hannover, Germany |
| Otto-von-Guericke University; Dept. of Endocrinology | Magdeburg, Germany, 39120 |
| Dept of Medicine I | Mainz, Germany |
| University of Munich, Dept. of Internal Medicine (Innenstadt) | Munich, Germany, 80336 |
| University of Wuerzburg - Dept. of Medicine | Wuerzburg, Germany, 97080 |
| University of Turin, Dept of Internal Medicine | Orbassano, Italy, 10043 |
| Clinica Endocrinologica, Università di Padova, Azienda Ospedaliera di Padova | Padova, Italy |
| Academisch Medisch Centrum; Dept. of Endocrinology | Amsterdam, Netherlands, 1105 AZ |
| Vrije Universiteit Medisch Centrum | Amsterdam, Netherlands, 1007 |
| Maxima Medisch Centrum; Dept. of Internal Medicine | Eindhoven, Netherlands, 5631 BM |
| University Hospital Groningen; Dept. of Internal Medine | Groningen, Netherlands, 9700 |
| 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, Sweden, 751 85 |