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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: First International Randomized Trial in Locally Advanced and Metastatic Adrenocortical Carcinoma Treatment

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 Summary:

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.


Sponsor: Collaborative Group for Adrenocortical Carcinoma Treatment

Current 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


Original Primary Outcome: Overall Survival

Current Secondary Outcome:

  • 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


Original Secondary Outcome:

  • Time to progression (TTP)
  • Quality of life as measured by QLQ-C30
  • Best overall response rate and duration of response
  • Number of Disease-free Patients
  • Impact of reaching mitotane blood levels between 14-20
  • mg/l in both arms on survival and overall response rate
  • TTP of both regimens as second line treatment in case of failure of the other initial regime


Information By: Collaborative Group for Adrenocortical Carcinoma Treatment

Dates:
Date Received: October 19, 2004
Date Started: June 2004
Date Completion:
Last Updated: September 19, 2016
Last Verified: September 2016