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

Carcinoma, Adrenal Cortical Clinical Trial

Official title:

First International Randomized Trial in Locally Advanced and Metastatic Adrenocortical Carcinoma Treatment

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00094497
• Other study ID #: CO-ACT-001
• Status: Completed
• Phase: Phase 3
• First received: October 19, 2004
• Last updated: September 19, 2016
• Start date: June 2004
• Est. completion date: December 2010

Study information

• Verified date: September 2016
• Source: Collaborative Group for Adrenocortical Carcinoma Treatment
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical DevicesSweden: Medical Products AgencyFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Italy: Ministry of HealthNetherlands: Independent Ethics CommitteeAustralia: Department of Health and Ageing Therapeutic Goods Administration
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00924144

Recruitment information / eligibility

• Status: Completed
• Enrollment: 304
• Est. completion date: December 2010
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adrenocortical Carcinoma
• Carcinoma
• Carcinoma, Adrenal Cortical

Intervention

Drug:
• Etoposide

• Doxorubicin

• Cisplatin

• Streptozotocin

• Mitotane

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide
Austria	University of Graz	Graz
France	Clinique Marc Linquette	Lille
France	Centre Leon Berard	Lyon
France	Hospital de Marseille la timone	Marseille
France	Cochin Hospital	Paris
France	Hospital Bordeaux haut leveque	Pessac
France	Institut Gustave Roussy	Villejuif
Germany	Charité-Universitätsmedizin Berlin - Campus Mitte	Berlin
Germany	Charité-University, Dept. of Endocrinology; Campus Benjamin Franklin	Berlin
Germany	Dept. of Medicine III	Dresden
Germany	University of Duesseldorf, Dept. of Endocrrinology	Duesseldorf
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
Germany	Dept of Medicine I	Mainz
Germany	University of Munich, Dept. of Internal Medicine (Innenstadt)	Munich
Germany	University of Wuerzburg - Dept. of Medicine	Wuerzburg
Italy	University of Turin, Dept of Internal Medicine	Orbassano
Italy	Clinica Endocrinologica, Università di Padova, Azienda Ospedaliera di Padova	Padova
Netherlands	Academisch Medisch Centrum; Dept. of Endocrinology	Amsterdam
Netherlands	Vrije Universiteit Medisch Centrum	Amsterdam
Netherlands	Maxima Medisch Centrum; Dept. of Internal Medicine	Eindhoven
Netherlands	University Hospital Groningen; Dept. of Internal Medine	Groningen
Netherlands	Leiden University Medical Center	Leiden
Sweden	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
United States	University of Michigan, Department of Internal Medicine	Ann Arbor	Michigan
United States	National Cancer Institute - Center for Cancer Research	Bethesda	Maryland

Sponsors (3)

Lead Sponsor	Collaborator
Collaborative Group for Adrenocortical Carcinoma Treatment	German Federal Ministry of Education and Research, National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Australia,  Austria,  France,  Germany,  Italy,  Netherlands,  Sweden, 

References & 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, Tabar — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	No
Other	Pharmakinetics of Mitotane (Substudy)	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).	11 time points in the first 12 weeks	No
Other	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	No
Primary	Overall Survival	participants who died among those randomized to first-line therapy	every 8 weeks until death up to 5 years	No
Secondary	Progression-free Survival		every 8 weeks until progression or death up to 5 years	No
Secondary	Change in Quality of Life as Measured by QLQ-C30	scale ranged from 0 to 100 with higher score meaning greater quality of life	baseline and 8 weeks	Yes
Secondary	Best Overall Response Rate	RECIST 1.0 was used to evaluate response	every 8 weeks up to 5 years	No
Secondary	Number of Disease-free Patients	complete response or disease-free by time of surgery	every 8 weeks until progression (up to 5 years)	No

External Links

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