First International Randomized Trial in Locally Advanced and Metastatic Adrenocortical Carcinoma Treatment
18 Years
N/A
Both
Carcinoma, Adrenal Cortical
Trial Information
First International Randomized Trial in Locally Advanced and Metastatic Adrenocortical Carcinoma Treatment
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.
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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Overall survival
Outcome Time Frame:
At the final analysis
Safety Issue:
No
Principal Investigator
Britt Skogseid, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Uppsala University Hospital
Authority:
Germany: Federal Institute for Drugs and Medical Devices
Study ID:
CO-ACT-001
NCT ID:
NCT00094497
Start Date:
June 2004
Completion Date:
December 2010
Related Keywords:
- Carcinoma, Adrenal Cortical
- Carcinoma
- Adrenocortical Carcinoma
Name | Location |
|---|---|
| National Cancer Institute - Center for Cancer Research | Bethesda, Maryland |
| University of Michigan, Department of Internal Medicine | Ann Arbor, Michigan 48109 |
