Sunitinib in Refractory Adrenocortical Carcinoma (SIRAC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00453895
Recruitment Status : Unknown
Verified July 2010 by University of Wuerzburg.
Recruitment status was:  Active, not recruiting
First Posted : March 29, 2007
Last Update Posted : July 7, 2010
Information provided by:
University of Wuerzburg

Brief Summary:

Although a first randomized trial in patients with advanced ACC leading to the establishment of a first line cytotoxic chemotherapy is ongoing (FIRM-ACT), the failure rate even of this FIRM-ACT study is most likely clearly above 50%. Therefore, the majority of participating patients urgently need a new treatment option. However, up to date there is no evidence for a single regimen that might be promising in these treatment-refractory patients with ACC.

Sunitinib is an oral multitargeted tyrosine kinase inhibitor with anti-tumor and antiangiogenic activities, which is successfully tested in the treatment of patients with metastatic renal cell carcinoma, gastrointestinal stromal and neuroendocrine tumors after failure of standard cytotoxic chemotherapy.

The primary objective of this trial is to estimate the response (defined as progression-free survival of ≥ 12 weeks) rate associated with Sunitinib treatment in patients advanced ACC progressing after cytotoxic chemotherapy.

Condition or disease Intervention/treatment Phase
Adrenocortical Carcinoma Drug: Sunitinib Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Sunitinib in Refractory Adrenocortical-Carcinoma Patients Progressing After Cytotoxic Chemotherapy
Study Start Date : July 2007
Estimated Primary Completion Date : October 2010
Estimated Study Completion Date : June 2011

Primary Outcome Measures :
  1. Assessment of clinical benefit as measured by non progressing rate after 12 weeks of treatment with Sunitinib

Secondary Outcome Measures :
  1. Assessment of Objective Response Rates (ORR) and duration of response (DR)
  2. Assessment of progression-free survival
  3. Assessment of overall survival
  4. Assessment of the relationship between specific "biomarker" and cancer- and treatment-related outcomes
  5. Assessment of quality of life by EORTC QLQ-C30
  6. Assessment of toxicity

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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 ACC
  • Locally advanced or metastatic disease not amenable to radical surgery resection
  • Radiologically monitorable disease
  • Progressing disease after one to three cytotoxic chemotherapy regimes including a platin-based protocol
  • ECOG performance status 0-2
  • Life expectancy ≥ 3 months
  • Age ≥ 18 years
  • Adequate bone marrow reserve (neutrophils ≥ 1500/mm³ and platelets ≥100.000/mm³) and haemoglobin ≥ 9 g/dl
  • Negative pregnancy test and effective contraception in pre-menopausal female and male patients
  • Patient´s written informed consent
  • Ability to comply with the protocol procedures
  • If patients have been participated in another clinical trial evaluating treatment options for ACC (e.g. FIRM-ACT), the patient can only be included in the SIRAC trial, if:

    • the patient has discontinued study treatment of the previous trial according to the protocol
    • or the study chair of the previous trial gives written approval for inclusion of this individual patient in the SIRAC trial.

Exclusion Criteria:

  • History of prior malignancy, except for cured non-melanoma skin cancer, cured in situ cervical carcinoma, or other treated malignancies with no evidence of disease for at least three years.
  • Severe renal (serum creatinine > 2.5 x ULN) or hepatic insufficiency (ALT / AST > 2.5 x ULN or ALT/AST >5 x ULN if liver function abnormalities are due to the underlying malignancy and/or total serum bilirubin > 2.0 x ULN) and/or serum albumin < 3g/dl
  • Any of the following within the 8 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, or other severe thromboembolic event.
  • Ongoing cardiac dysrhythmias of NCI CTCAE grade 2, acute atrial fibrillation of any grade, or prolongation of the QTc interval to >470 msec for females
  • Left ventricular ejection fraction (LVEF) <45% as measured by echocardiogram
  • NCI CTCAE Grade 3 hemorrhage within 4 weeks of starting study treatment
  • Hypertension that cannot be controlled by medications (>160/100 mmHg despite optimal medical therapy)
  • Pregnancy or breast feeding
  • Previous treatment with Sunitinib or any other VEGF- or PDGF-pathway directed agent.
  • Current treatment with strong CYP3A4 inhibitors or -inducers
  • Current treatment with another investigational drug
  • Current treatment with another anti-cancer drug
  • Patients with ileus within the last 28 days
  • Major surgery, radiation therapy, or systemic therapy within 3 weeks of first study treatment. At least 7 days should elapse from the time of minor surgical procedure including placement of an access device or fine needle aspiration before start of study treatment
  • Serious wounds that have not completely healed, active ulcer(s), or significant bone fracture(s).
  • Prior radiation therapy to >25% of the bone marrow.
  • Cachectic patients with a body mass index < 18 kg/m2
  • Any other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration, or which, in the judgment of the investigator, would make the patient inappropriate for entry into this study.

Information from the National Library of Medicine

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 identifier (NCT number): NCT00453895

Charite Berlin
Berlin, Germany
Dept. of Medicine I, University of Wuerzburg
Wuerzburg, Germany, 97080
Sponsors and Collaborators
University of Wuerzburg
Principal Investigator: Martin Fassnacht, MD University of Wuerzburg Identifier: NCT00453895     History of Changes
Other Study ID Numbers: SIRAC-1
First Posted: March 29, 2007    Key Record Dates
Last Update Posted: July 7, 2010
Last Verified: July 2010

Keywords provided by University of Wuerzburg:
Adrenal cancer refractory to cytotoxic therapy
Multitargeted tyrosine-kinase inhibitor

Additional relevant MeSH terms:
Adrenocortical Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Adrenal Cortex Neoplasms
Adrenal Gland Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Adrenal Cortex Diseases
Adrenal Gland Diseases
Endocrine System Diseases
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors