First International Randomised trial in Locally Advanced and Metastatic Adrenocortical Cancer Treatment - Etoposide, Doxorubicin, Cisplatin and Mitotane versus Streptozotocin and Mitotane

ISRCTN	ISRCTN94256573
DOI	https://doi.org/10.1186/ISRCTN94256573
Secondary identifying numbers	CO-ACT-001

Submission date: 22/08/2005
Registration date: 16/09/2005
Last edited: 20/08/2008

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Study website

Contact information

Prof Britt Skogseid
Scientific

University Hospital Uppsala
Entrance 40, 5th floor
Uppsala
75185
Sweden

Phone	+46 186113768
Email	britt.skogseid@medsci.uu.se

Study information

Study design	Randomised controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Not specified
Study type	Treatment
Scientific title
Study acronym	FIRM-ACT
Study objectives	Primary objective of this trial is to investigate whether Etoposide, Doxorubicin, Cisplatin plus Mitotane (EDP-M) as first line treatment will prolong survival as compared to Streptozotocin plus Mitotane (Sz-M) as first line treatment for advanced Adrenocortical Carcinoma (ACC).
Ethics approval(s)	Not provided at time of registration
Health condition(s) or problem(s) studied	Adrenocortical Carcinoma
Intervention	Etoposide, Doxorubicin, Cisplatin plus Mitotane (EDP/M) or Streptozotocin plus Mitotane (Sz/M) as first line treatment. The syudy protocol is available on http://www.firm-act.org/documents/FIRM_ACT_Synopsis.pdf and http://www.firm-act.org/documents/FIRM_ACT_protocol_final.pdf
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Etoposide, Doxorubicin, Cisplatin and Mitotane versus Streptozotocin and Mitotane
Primary outcome measure	Overall survival
Secondary outcome measures	1. Quality of life as measured by EORTC QLQ-C30 2. Time to progression 3. Best overall response rate and duration of response 4. Number of disease-free patients 5. Impact of reaching mitotane blood levels between 14-20 mg/l in both arms on survival and best overall response rate 6. Best overall response rate of both regimens as second line treatment in case of failure of the initial other regime
Overall study start date	01/07/2004
Completion date	31/12/2011

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	300
Key inclusion criteria	1. Histologically confirmed diagnosis of adrenocortical carcinoma 2. Locally advanced or metastatic disease not amenable to radical surgical resection (Stage III-IV) 3. Radiologically monitorable disease 4. Eastern Cooperative Oncology Group (ECOG) performance status zero to two 5. Life expectancy more than three months 6. Age above 18 years 7. Adequate bone marrow reserve (neutrophils more than or equal to 1500/mm^3 and platelets more than or equal to 100,000/mm^3) 8. Effective contraception in pre-menopausal female and male patients 9. Patients written informed consent 10. Ability to comply with the protocol procedures (including availability for follow-up visits) 11. Previous palliative surgery, radiotherapy or radiofrequency ablation is acceptable as long as radiologically monitorable disease is verifiable afterwards.
Key exclusion criteria	1. History of prior malignancy, except for cured non-melanoma skin cancer, cured in situ cervical carcinoma, or other cancers treated with no evidence of disease for at least five years 2. Previous cytotoxic chemotherapy (prior therapy with mitotane is allowed) for adrenocortical carcinoma 3. Renal insufficiency (serum creatinine more than or equal to 2 mg/dl or creatinine clearance less than or equal to 50 ml/min) 4. Hepatic insufficiency (serum bilirubin more than or equal to two times the institutional upper limit of normal range and/or serum transaminases more than or equal to three times the institutional upper limit of normal range; exception: in patients on mitotane transaminase levels up to five times the institutional upper limit of normal range are acceptable) 5. Pregnancy or breast feeding 6. Known hypersensitivity to any drug included in the treatment protocol 7. Presence of active infection 8. 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 9. Decompensated heart failure (ejection fraction less than 50%), myocardial infarction or revascularization procedure during the last six months, unstable angina pectoris, and uncontrolled cardiac arrhythmia 10. Current treatment with other experimental drugs and/or previous participation in clinical trials with other experimental agents for adrenocortical carcinoma 11. Prisoners
Date of first enrolment	01/07/2004
Date of final enrolment	31/12/2011

Locations

Countries of recruitment

Australia
France
Germany
Italy
Netherlands
Sweden
United States of America

Study participating centre

University Hospital Uppsala

Uppsala
75185
Sweden

Sponsor information

Collaborative group for Adrenocortical Carcinoma Therapy (CO-ACT) (Germany)
Research organisation

c/o University Hospital Uppsala (Sweden) and University Hospital Wuerzburg (Germany)
Josef-Schneider-Str. 2
Wuerzburg
97080
Germany

Phone	+49 (0) 931 201 36507
Email	Fassnacht_m@medizin.uni-wuerzburg.de
Website	http://www.firm-act.org

Funders

Funder type

Hospital/treatment centre

Investigator funded trial (CO-ACT)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan