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

This study has been completed.
Sponsor:
Collaborators:
German Federal Ministry of Education and Research
Information provided by:
Collaborative Group for Adrenocortical Carcinoma Treatment
ClinicalTrials.gov Identifier:
NCT00094497
First received: October 19, 2004
Last updated: May 14, 2012
Last verified: May 2012

October 19, 2004
May 14, 2012
June 2004
December 2010   (final data collection date for primary outcome measure)
Overall survival [ Time Frame: At the final analysis ] [ Designated as safety issue: No ]
Overall survival
Complete list of historical versions of study NCT00094497 on ClinicalTrials.gov Archive Site
  • Time to progression (TTP) [ Time Frame: At each evaluation (every 8 weeks) ] [ Designated as safety issue: No ]
  • Quality of life as measured by QLQ-C30 [ Time Frame: at each evaluation ] [ Designated as safety issue: Yes ]
  • Best overall response rate and duration of response [ Time Frame: At each evaluation (every 8 weeks) ] [ Designated as safety issue: No ]
  • Number of disease-free patients [ Designated as safety issue: No ]
  • Impact of reaching mitotane blood levels between 14-20 mg/l in both arms on survival and overall response rate [ Designated as safety issue: No ]
  • TTP of both regimens as second line treatment in case of failure of the other initial regime [ Designated as safety issue: No ]
  • Pharmakinetics of mitotane (substudy) [ Time Frame: 11 time points in the first 12 weeks ] [ Designated as safety issue: No ]
    To study the relationship between mitotane dose (daily and cumulative) and mitotane plasma concentrations using one of two pre-defined treatment regimens (high-dose and low-dose).
  • 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
Not Provided
Not Provided
 
Trial in Locally Advanced and Metastatic Adrenocortical Carcinoma Treatment (FIRM-ACT)
First International Randomized Trial in Locally Advanced and Metastatic Adrenocortical Carcinoma Treatment

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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Carcinoma, Adrenal Cortical
  • Drug: Etoposide
  • Drug: Doxorubicin
  • Drug: Cisplatin
  • Drug: Streptozotocin
  • Drug: Mitotane
Not Provided
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 Fouchardière C, Schlumberger M, Mantero F, Weismann D, Beuschlein F, Gelderblom H, Wilmink H, Sender M, Edgerly M, Kenn W, Fojo T, Müller 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
300
December 2010
December 2010   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Netherlands,   France,   Germany,   Italy,   Sweden,   United States,   Australia,   Austria
 
NCT00094497
CO-ACT-001
Yes
Martin Fassnacht + Britt Skogseid, University of Würzburg + University of Uppsala
Collaborative Group for Adrenocortical Carcinoma Treatment
  • German Federal Ministry of Education and Research
  • National Cancer Institute (NCI)
Study Chair: Britt Skogseid, MD Uppsala University Hospital
Principal Investigator: Martin Fassnacht, MD University of Würzburg
Collaborative Group for Adrenocortical Carcinoma Treatment
May 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP