Carcinoma, Adrenal CorticalPhase 3NCT00094497
Trial in Locally Advanced and Metastatic Adrenocortical Carcinoma Treatment (FIRM-ACT)
A Phase 3 study testing Etoposide, Doxorubicin and Cisplatin in people with Carcinoma, Adrenal Cortical, run by Collaborative Group for Adrenocortical Carcinoma Treatment at 32 sites in 8 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Adrenal Cortical
- What is being tested?
- Etoposide, Doxorubicin and Cisplatin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 304 participants
- Where
- 32 sitesin 8 countries
- Study dates
- Jun 2004to Dec 2010
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
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- 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
Trial locations and contacts
32 sites in 8 countries.
32 sites in 8 countries
Germany10 sites
Charité-University, Dept. of Endocrinology; Campus Benjamin Franklin
Berlin
Charité-Universitätsmedizin Berlin - Campus Mitte
Berlin
Dept. of Medicine III
Dresden
University of Duesseldorf, Dept. of Endocrrinology
Düsseldorf, 40001
Zentrum für Innere Medizin - Endokrinologie des Universitätsklinikum Essen
Essen
Endokrinologie Medizinische Hochschule Hannover
Hanover
Otto-von-Guericke University; Dept. of Endocrinology
Magdeburg, 39120
Dept of Medicine I
Mainz
University of Munich, Dept. of Internal Medicine (Innenstadt)
Munich, 80336
University of Wuerzburg - Dept. of Medicine
Würzburg, 97080
France6 sites
Clinique Marc Linquette
Lille
Centre Leon Berard
Lyon
Hospital de Marseille la timone
Marseille, 13385
Cochin Hospital
Paris, 75679
Hospital Bordeaux haut leveque
Pessac, 33600
Institut Gustave Roussy
Villejuif, 94805
Netherlands5 sites
Vrije Universiteit Medisch Centrum
Amsterdam, 1007
Academisch Medisch Centrum; Dept. of Endocrinology
Amsterdam, 1105 AZ
Maxima Medisch Centrum; Dept. of Internal Medicine
Eindhoven, 5631 BM
University Hospital Groningen; Dept. of Internal Medine
Groningen, 9700
Leiden University Medical Center
Leiden
Sweden5 sites
Department of Oncology, Sahlgrenska University Hospital
Gothenburg
Department of Oncology, Linköping University Hospital
Linköping
Department of Medicine, The Jubileum Institute, Lund University
Lund
Dept of Surgery, Karolinska Hospital, Stockholm
Stockholm
Uppsala University Hospital - Dept of Medical Sciences
Uppsala, 751 85
United States2 sites
University of Michigan, Department of Internal Medicine
Ann Arbor, Michigan, 48109
National Cancer Institute - Center for Cancer Research
Bethesda, Maryland
Italy2 sites
University of Turin, Dept of Internal Medicine
Orbassano, 10043
Clinica Endocrinologica, Università di Padova, Azienda Ospedaliera di Padova
Padova
About this study
Official title: 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.
Read the 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.
- Conditions
- Carcinoma, Adrenal Cortical
- Being tested
- Etoposide, Doxorubicin, Cisplatin, Streptozotocin, Mitotane
- Medical subject headings
- Adrenocortical Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EtoposideDrug
DoxorubicinDrug
CisplatinDrug
StreptozotocinDrug
MitotaneDrug
| Study group | Role | What they receive |
|---|---|---|
| EDP-M | Active comparator | etopodide, doxorubicin, cisplatin and mitotane Receives: Drug: Etoposide; Drug: Doxorubicin; Drug: Cisplatin; Drug: Mitotane |
| Sz-M | Active comparator | streptozotocin and mitotane Receives: Drug: Streptozotocin; Drug: Mitotane |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival
participants who died among those randomized to first-line therapy
Measured: every 8 weeks until death up to 5 years
Secondary outcomes (4)
Progression-free Survival
Measured: every 8 weeks until progression or death up to 5 years
Change in Quality of Life as Measured by QLQ-C30
scale ranged from 0 to 100 with higher score meaning greater quality of life
Measured: baseline and 8 weeks
Best Overall Response Rate
RECIST 1.0 was used to evaluate response
Measured: every 8 weeks up to 5 years
Number of Disease-free Patients
complete response or disease-free by time of surgery
Measured: every 8 weeks until progression (up to 5 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2004 (estimated)
- Study startJun 2004
- Primary completionDec 2010
- Study completionDec 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Carcinoma, Adrenal CorticalStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 304 participants (actual)
Sponsor and investigators
- Lead sponsor
- Collaborative Group for Adrenocortical Carcinoma Treatment
- Sponsor type
- University, hospital or other
- Collaborators
- German Federal Ministry of Education and Research, National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Martin Fassnacht, Collaborative Group for Adrenocortical Carcinoma Treatment
- Investigators
- Britt Skogseid, MD, Study chair, Uppsala University HospitalMartin Fassnacht, MD, Principal investigator, University of Würzburg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00094497
- Sponsor's protocol ID
- CO-ACT-001
- Status last verified
- Sep 2016
- First submitted
- 19 Oct 2004
- Last updated
- 21 Sep 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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 Fouchardiere C, Schlumberger M, Mantero F, Weismann D, Beuschlein F, Gelderblom H, Wilmink H, Sender M, Edgerly M, Kenn W, Fojo T, Muller 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.
PubMed 22551107
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- First International Randomized Trial in Locally Advanced and Metastatic Adrenocortical Carcinoma Treatment
- ClinicalTrials.gov ID
- NCT00094497
- Acronym / sponsor ID
- CO-ACT-001
- Conditions
- Carcinoma, Adrenal Cortical
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 304 participants (actual)
- Lead sponsor
- Collaborative Group for Adrenocortical Carcinoma TreatmentUniversity, hospital or other
- Collaborators
- German Federal Ministry of Education and Research, National Cancer Institute (NCI)
- Study start
- Jun 2004
- Primary completion
- Dec 2010 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 20 Oct 2004 (estimated)
- Results
- Posted 21 Sep 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| EDP-M | Active comparator | Drug: Etoposide, Drug: Doxorubicin, Drug: Cisplatin, Drug: Mitotaneetopodide, doxorubicin, cisplatin and mitotane |
| Sz-M | Active comparator | Drug: Streptozotocin, Drug: Mitotanestreptozotocin and mitotane |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Etoposide | Drug | EDP-M |
| Doxorubicin | Drug | EDP-M |
| Cisplatin | Drug | EDP-M |
| Streptozotocin | Drug | Sz-M |
| Mitotane | Drug | EDP-M, Sz-M |
Primary outcome
Overall Survival
Time frame: every 8 weeks until death up to 5 years
participants who died among those randomized to first-line therapy
4 secondary outcomes
Progression-free Survival
Time frame: every 8 weeks until progression or death up to 5 years
Change in Quality of Life as Measured by QLQ-C30
Time frame: baseline and 8 weeks
Best Overall Response Rate
Time frame: every 8 weeks up to 5 years
Number of Disease-free Patients
Time frame: every 8 weeks until progression (up to 5 years)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22551107Fassnacht 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 Fouchardiere C, Schlumberger M, Mantero F, Weismann D, Beuschlein F, Gelderblom H, Wilmink H, Sender M, Edgerly M, Kenn W, Fojo T, Muller 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Britt Skogseid, MD study chair
Uppsala University Hospital
Martin Fassnacht, MD principal investigator
University of Würzburg
32 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Etoposide, Doxorubicin and Cisplatin in people with Carcinoma, Adrenal Cortical, run by Collaborative Group for Adrenocortical Carcinoma Treatment at 32 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 32 sites in Germany, France, Netherlands, Sweden, United States and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Sep 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (time frame: every 8 weeks until death up to 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00094497, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2016.