FIRM-ACT: First International Randomised trial in Locally Advanced and Metastatic Adrenocortical Cancer Treatment - Etoposide, Doxorubicin, Cisplatin and Mitotane versus Streptozotocin and Mitotane

Inclusion criteria:
1. Histologically confirmed diagnosis of adrenocortical carcinoma
2. Locally advanced or metastatic disease not amenable to radical surgical resection (Stage III-IV)
3. Radiologically monitorable disease
4. Eastern Cooperative Oncology Group (ECOG) performance status zero to two
5. Life expectancy more than three months
6. Age above 18 years
7. Adequate bone marrow reserve (neutrophils more than or equal to 1500/mm^3 and platelets more than or equal to 100,000/mm^3)
8. Effective contraception in pre-menopausal female and male patients
9. Patient’s written informed consent
10. Ability to comply with the protocol procedures (including availability for follow-up visits)
11. Previous palliative surgery, radiotherapy or radiofrequency ablation is acceptable as long as radiologically monitorable disease is verifiable afterwards.

Exclusion criteria:
1. History of prior malignancy, except for cured non-melanoma skin cancer, cured in situ cervical carcinoma, or other cancers treated with no evidence of disease for at least five years
2. Previous cytotoxic chemotherapy (prior therapy with mitotane is allowed) for adrenocortical carcinoma
3. Renal insufficiency (serum creatinine more than or equal to 2 mg/dl or creatinine clearance less than or equal to 50 ml/min)
4. Hepatic insufficiency (serum bilirubin more than or equal to two times the institutional upper limit of normal range and/or serum transaminases more than or equal to three times the institutional upper limit of normal range; exception: in patients on mitotane transaminase levels up to five times the institutional upper limit of normal range are acceptable)
5. Pregnancy or breast feeding
6. Known hypersensitivity to any drug included in the treatment protocol
7. Presence of active infection
8. 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
9. Decompensated heart failure (ejection fraction less than 50%), myocardial infarction or revascularization procedure during the last six months, unstable angina pectoris, and uncontrolled cardiac arrhythmia
10. Current treatment with other experimental drugs and/or previous participation in clinical trials with other experimental agents for adrenocortical carcinoma 
11. Prisoners

• US trials at ordinary hospitals: routine care is billed

  In the US a sponsor funds the study drug and study-specific scans, but the routine care around them is billed to insurance. Without US cover that bill falls on you.

  Cost is documented as the barrier that stops roughly 45 percent of US patients joining trials, before any question of being a non-resident. Eligibility on paper does not make a US site reachable. One email to the study coordinator asking what a non-resident without US insurance would be billed settles it either way.

  Verify with: The study coordinator listed on the registry record

  Ask first; potentially very high

• Free patient navigation

  myTomorrows (Amsterdam) provides medically trained, multilingual patient navigators who search ClinicalTrials.gov, EU CTIS and ISRCTN and can support a doctor through an expanded-access application. Free to patients and families.

  A navigator keeps searching after any single page stops being current. Use it alongside this site, not instead of your oncologist.

  Verify with: myTomorrows for patients

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