Trial in Locally Advanced and Metastatic Adrenocortical Carcinoma Treatment (FIRM-ACT)
Condition: Carcinoma, Adrenal Cortical
MeSH terms: Carcinoma; Adrenocortical Carcinoma
Intervention: Etoposide; Doxorubicin; Cisplatin; Streptozotocin; Mitotane
Intervention MeSH terms: Doxorubicin; Etoposide; Mitotane; Streptozocin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 304.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

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