Trial in Locally Advanced and Metastatic Adrenocortical Carcinoma Treatment (FIRM-ACT)
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| ClinicalTrials.gov Identifier: NCT00094497 |
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Recruitment Status :
Completed
First Posted : October 20, 2004
Results First Posted : September 21, 2016
Last Update Posted : September 21, 2016
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Carcinoma, Adrenal Cortical | Drug: Etoposide Drug: Doxorubicin Drug: Cisplatin Drug: Streptozotocin Drug: Mitotane | Phase 3 |
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 Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 304 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | First International Randomized Trial in Locally Advanced and Metastatic Adrenocortical Carcinoma Treatment |
| Study Start Date : | June 2004 |
| Actual Primary Completion Date : | December 2010 |
| Actual Study Completion Date : | December 2010 |
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: EDP-M
etopodide, doxorubicin, cisplatin and mitotane
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Drug: Etoposide Drug: Doxorubicin Drug: Cisplatin Drug: Mitotane |
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Active Comparator: Sz-M
streptozotocin and mitotane
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Drug: Streptozotocin Drug: Mitotane |
- Overall Survival [ Time Frame: every 8 weeks until death up to 5 years ]participants who died among those randomized to first-line therapy
- 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 ]scale ranged from 0 to 100 with higher score meaning greater quality of life
- Best Overall Response Rate [ Time Frame: every 8 weeks up to 5 years ]RECIST 1.0 was used to evaluate response
- Number of Disease-free Patients [ Time Frame: every 8 weeks until progression (up to 5 years) ]complete response or disease-free by time of surgery
- TTP of Both Regimens as Second Line Treatment in Case of Failure of the Other Initial Regime [ Time Frame: every 8 weeks until progression or until Dec 2010 ]
- Pharmakinetics of Mitotane (Substudy) [ Time Frame: 11 time points in the first 12 weeks ]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).
- Impact of Reaching Mitotane Blood Levels Between 14-20 mg/l in Both Arms on Survival and Overall Response Rate [ Time Frame: every 8 weeks until progression or until Dec 2010 ]
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00094497
Show 32 study locations
| Study Chair: | Britt Skogseid, MD | Uppsala University Hospital | |
| Principal Investigator: | Martin Fassnacht, MD | University of Würzburg |
Publications of Results:
| Responsible Party: | Martin Fassnacht, Co-PI, Collaborative Group for Adrenocortical Carcinoma Treatment |
| ClinicalTrials.gov Identifier: | NCT00094497 |
| Obsolete Identifiers: | NCT00924144 |
| Other Study ID Numbers: |
CO-ACT-001 |
| First Posted: | October 20, 2004 Key Record Dates |
| Results First Posted: | September 21, 2016 |
| Last Update Posted: | September 21, 2016 |
| Last Verified: | September 2016 |
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Carcinoma Adrenocortical Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Adenocarcinoma Adrenal Cortex Neoplasms Adrenal Gland Neoplasms Endocrine Gland Neoplasms Neoplasms by Site Adrenal Cortex Diseases Adrenal Gland Diseases Endocrine System Diseases |
Doxorubicin Etoposide Mitotane Streptozocin Antineoplastic Agents Antibiotics, Antineoplastic Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents, Phytogenic Antineoplastic Agents, Hormonal |