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Sorafenib Plus Paclitaxel Metronomic Chemotherapy in Adreno-Cortical-Carcinoma Patients Progressing After 1st or 2nd Line Cytotoxic Chemotherapy

Phase 2
18 Years
70 Years
Open (Enrolling)
Adrenocortical Carcinoma

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Trial Information

Sorafenib Plus Paclitaxel Metronomic Chemotherapy in Adreno-Cortical-Carcinoma Patients Progressing After 1st or 2nd Line Cytotoxic Chemotherapy

The study is designed as a Phase II, prospective, non randomized, open-label, single arm,
multicenter trial, in which patients with locally advanced or metastatic ACC not amenable to
complete surgical resection.


The aim of this phase II trial is to evaluate the clinical benefit and toxicity of the
combination of Sorafenib plus metronomic chemotherapy in patients with locally advanced or
metastatic ACC who progressed after first or second line chemotherapy.

Primary objective

To assess the clinical benefit as measured by a non progressing rate after 4 months of the
combination of Sorafenib plus weekly Paclitaxel in patients with locally advanced or
metastatic ACC who progressed after first or second line chemotherapy.

Secondary objectives

- Assessment of Objective (Complete and Partial) Response Rates

- Assessment of Duration of Response

- Assessment of Hormonal Response

- Assessment of Progression-Free Survival

- Assessment of Overall Survival

- Assessment of the relationship between specific "biomarkers" and cancer- and
treatment-related outcomes

- Assessment of Quality of Life by EORTC QLQ-C30

- Assessment of Toxicity


The first disease assessment will be performed after 8-weeks, subsequent assessments will be
performed every 12 weeks until end of the study.

Primary endpoint

- Progression-Free Survival rate ≥ 40% after 4 months

Secondary endpoints

- Response rate evaluation will be performed according to the RECIST criteria. The same
methods of measurement and the same technique should be used to characterize each
identified and reported lesion at baseline and during study.

TREATMENT SCHEME Treatment scheme consisted of oral Sorafenib 400 mg p.o. bid plus
intravenous Paclitaxel 60 mg/mq/weekly i.v., until disease progression.

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 or two cytotoxic chemotherapy regimens (including a
platin-based protocol)

- ECOG performance status 0-2

- Life expectancy ≥ 3 months

- Subjects with at least one uni-dimensional(for RECIST) or bi-dimensional(for WHO)
measurable lesion. Lesions must be measured by CT-scan or MRI

- Age ≥ 18 years

- Adequate bone marrow reserve (neutrophils ≥ 1500/mm³ and platelets ≥ 80.000/mm³)

- Hemoglobin > 9.0 g/dl

- Total bilirubin < 1.5 times the upper limit of normal

- PT-INR/PTT < 1.5 x upper limit of normal [Patients who are being therapeutically
anticoagulated with an agent such as coumadin or heparin will be allowed to
participate provided that no prior evidence of underlying abnormality in these
parameters exists.]

- Serum creatinine < 1.5 x upper limit of normal

- Effective contraception in pre-menopausal female and male patients

- Patient´s written informed consent

- Ability to comply with the protocol procedures

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.

- History of HIV infection or chronic hepatitis B or C (This criteria should be
modified to allow Hepatitis B or C in protocols looking at HCC patient population)

- Active clinically serious infections (> grade 2 NCI-CTC version 3.0)

- Symptomatic metastatic brain or meningeal tumors (unless the patient is > 6 months
from definitive therapy, has a negative imaging study within 4 weeks of study entry
and is clinically stable with respect to the tumor at the time of study entry)

- Patients with seizure disorder requiring medication (such as steroids or

- History of organ allograft The organ allograft may be allowed as protocol specific

- 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 > 2.5 x ULN)

- Concomitant Rifampicin

- Concomitant St. John's Wort (Hypericum perforatum)

- Warfarin is allowed; however, close monitoring of Prothrombin Time (PT) is

- Decompensated heart failure (ejection fraction <45%), myocardial infarction or
revascularization procedure during the last 6 months, unstable angina pectoris,
uncontrolled cardiac arrhythmia

- Hypertension that cannot be controlled by medications (>160/100 mmHg despite optimal
medical therapy)

- Patients with recent or active bleeding diathesis

- Pregnant or breast-feeding patients. Women of childbearing potential must have a
negative pregnancy test performed within 7 days of the start of treatment.

- Both men and women enrolled in this trial must use adequate barrier birth control
measures during the course of the trial and three months after the completion of

- Previous treatment with Sorafenib or other anticancer chemotherapy or immunotherapy
during the study or within 4 weeks of study entry

- Radiotherapy during study or within 3 weeks of start of study drug. (Palliative
radiotherapy will be allowed).

- Major surgery within 4 weeks of start of study

- Autologous bone marrow transplant or stem cell rescue within 4 months of study

- Use of biologic response modifiers, such as G-CSF, within 3 week of study entry.
[G-CSF and other hematopoietic growth factors may be used in the management of acute
toxicity such as febrile neutropenia when clinically indicated or at the discretion
of the investigator, however they may not be substituted for a required dose
reduction.] [Patients taking chronic erythropoietin are permitted provided no dose
adjustment is undertaken within 2 months prior to the study or during the study]

- Current treatment with another investigational drug

- 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.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Disease free survival

Outcome Time Frame:

4 months

Safety Issue:


Principal Investigator

Alfredo Berruti MD

Investigator Role:

Study Chair

Investigator Affiliation:

Internal Medicine, Department of Clinical and Biological Sciences, University of Turin, Italy


Italy: The Italian Medicines Agency

Study ID:

EudraCT 2008-000759-91



Start Date:

April 2008

Completion Date:

October 2010

Related Keywords:

  • Adrenocortical Carcinoma
  • Sorafenib
  • Paclitaxel
  • Disease free survival
  • Carcinoma
  • Adrenocortical Carcinoma
  • Adrenal Cortex Neoplasms