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NCT00094497 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE3
Status at capture
COMPLETED
Registry last update
2016-09-21

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Overall Survival

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outcome · POSTED

Progression-free Survival

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outcome · POSTED

Change in Quality of Life as Measured by QLQ-C30

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outcome · POSTED

Best Overall Response Rate

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outcome · POSTED

Number of Disease-free Patients

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outcome · NOT POSTED

TTP of Both Regimens as Second Line Treatment in Case of Failure of the Other Initial Regime

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outcome · NOT POSTED

Pharmakinetics of Mitotane (Substudy)

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outcome · NOT POSTED

Impact of Reaching Mitotane Blood Levels Between 14-20 mg/l in Both Arms on Survival and Overall Response Rate

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
eligibility Criteria
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
healthy Volunteers
false
minimum Age
18 Years
sex
ALL
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    etopodide, doxorubicin, cisplatin and mitotane
    intervention Names
    1. Drug: Etoposide
    2. Drug: Doxorubicin
    3. Drug: Cisplatin
    4. Drug: Mitotane
    label
    EDP-M
    type
    ACTIVE_COMPARATOR
  2. description
    streptozotocin and mitotane
    intervention Names
    1. Drug: Streptozotocin
    2. Drug: Mitotane
    label
    Sz-M
    type
    ACTIVE_COMPARATOR
interventions
  1. arm Group Labels
    1. EDP-M
    name
    Etoposide
    type
    DRUG
  2. arm Group Labels
    1. EDP-M
    name
    Doxorubicin
    type
    DRUG
  3. arm Group Labels
    1. EDP-M
    name
    Cisplatin
    type
    DRUG
  4. arm Group Labels
    1. Sz-M
    name
    Streptozotocin
    type
    DRUG
  5. arm Group Labels
    1. EDP-M
    2. Sz-M
    name
    Mitotane
    type
    DRUG
Study design
allocation
RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
304
type
ACTUAL
Registered outcome plans (not posted results)
other Outcomes
  1. measure
    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
  2. description
    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).
    measure
    Pharmakinetics of Mitotane (Substudy)
    time Frame
    11 time points in the first 12 weeks
  3. measure
    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
primary Outcomes
  1. description
    participants who died among those randomized to first-line therapy
    measure
    Overall Survival
    time Frame
    every 8 weeks until death up to 5 years
secondary Outcomes
  1. measure
    Progression-free Survival
    time Frame
    every 8 weeks until progression or death up to 5 years
  2. description
    scale ranged from 0 to 100 with higher score meaning greater quality of life
    measure
    Change in Quality of Life as Measured by QLQ-C30
    time Frame
    baseline and 8 weeks
  3. description
    RECIST 1.0 was used to evaluate response
    measure
    Best Overall Response Rate
    time Frame
    every 8 weeks up to 5 years
  4. description
    complete response or disease-free by time of surgery
    measure
    Number of Disease-free Patients
    time Frame
    every 8 weeks until progression (up to 5 years)
Full study description
brief 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.
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.
Source references
references
  1. citation
    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.
    pmid
    22551107
    type
    RESULT
Source notices and limitations
    Discovery and provenance
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      1. context exact
        ozotocin or mitotane plus etoposide, doxorubicin, and cisplatin may be effective and has been compared in a phase III clinical trial (<a href="/clinicaltrials/NCT00924144">NCT00924144</a>) (under clinical evaluation).[<a href="#cit/section_6.2">2</a>]</li></ol></div><p id="_231" tabindex="-1">Many patients with functioning tumor
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      2. context exact
        itotane plus etoposide, doxorubicin, and cisplatin may be effective and has been compared in a phase III clinical trial (<a href="/clinicaltrials/NCT00924144">NCT00924144</a>) (under clinical evaluation).[<a href="#cit/section_6.2">2</a>]</li></ol></div><p id="_231" tabindex="-1">Many patients with functioning tumors who receive
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        exact text
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      3. context exact
        e.</li><li>Chemotherapy with mitotane plus streptozotocin or mitotane plus etoposide, doxorubicin, and cisplatin, as evidenced by the <a href="/clinicaltrials/NCT00924144">NCT00924144</a> phase III clinical trial.[<a href="#cit/section_7.1">1</a>]</li><li>Radiation therapy to bone metastases.</li><li> Surgical removal of localiz
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      4. context exact
        emotherapy with mitotane plus streptozotocin or mitotane plus etoposide, doxorubicin, and cisplatin, as evidenced by the <a href="/clinicaltrials/NCT00924144">NCT00924144</a> phase III clinical trial.[<a href="#cit/section_7.1">1</a>]</li><li>Radiation therapy to bone metastases.</li><li> Surgical removal of localized metastases
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      source title
      Adrenocortical Carcinoma Treatment (PDQ®)–Health Professional Version
      source update dates
      1. context
        Updated: December 13, 2024
        datetime
        2024-12-13T12:00:00Z
        display
        December 13, 2024

    Preserved source evidence · Not medical advice