Sorafenib Plus Paclitaxel in Adreno-Cortical-Cancer Patients (PAXO)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2009 by University of Turin, Italy.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
University of Turin, Italy
ClinicalTrials.gov Identifier:
NCT00786110
First received: November 5, 2008
Last updated: February 23, 2009
Last verified: February 2009
  Purpose

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 and progressing to cytotoxic chemotherapy will receive Sorafenib plus metronomic chemotherapy as treatment.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.


Condition Intervention Phase
Adrenocortical Carcinoma
Drug: Sorafenib
Drug: Paclitaxel
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Sorafenib Plus Paclitaxel Metronomic Chemotherapy in Adreno-Cortical-Carcinoma Patients Progressing After 1st or 2nd Line Cytotoxic Chemotherapy

Resource links provided by NLM:


Further study details as provided by University of Turin, Italy:

Primary Outcome Measures:
  • Disease free survival [ Time Frame: 4 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: 4 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: April 2008
Estimated Study Completion Date: October 2010
Estimated Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 arm only

One arm only with Sorafenib plus Paclitaxel Patients enrolled will undergo strict follow-up

Intervention: Sorafenib plus Paclitaxel

Drug: Sorafenib
Treatment scheme consisted of oral Sorafenib 400 mg p.o. bid until disease progression.
Drug: Paclitaxel
Intravenous Paclitaxel 60 mg/mq/weekly i.v., until disease progression.

Detailed Description:

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.

STUDY OBJECTIVES

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

ENDPOINTS

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 anti-epileptics)
  • 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 recommended
  • 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 trial
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00786110

Contacts
Contact: Fulvia Daffara +390119026 ext Ext. 992 fulviaclaudia@libero.it
Contact: Sperone Sperone +390119026 ext Ext. 017 paola.sperone@email.it

Locations
Italy
Department of Clinical and Biological Sciences, University of Turin Recruiting
Orbassano, Italy
Contact: Paola Perotti    : +390119026 ext Ext. 017      
Principal Investigator: Alfredo Berruti         
Azienda Ospedaliera di Padova Not yet recruiting
Padova, Italy
Contact: Franco Mantero         
Sub-Investigator: Franco Mantero         
Azienda Ospedaliera Università di Palermo Not yet recruiting
Palermo, Italy
Sub-Investigator: Vittorio Gebbia         
Policlinico Universitario Campus Biomedico- Roma Not yet recruiting
Roma, Italy
Contact: Daniele Santini         
Sub-Investigator: Daniele Santini         
Ist. Clin.Humanitas Not yet recruiting
Rozzano, Italy
Contact: Carlo Carnaghi         
Sub-Investigator: Carlo Carnaghi         
Sponsors and Collaborators
University of Turin, Italy
Investigators
Study Chair: Alfredo Berruti MD Internal Medicine, Department of Clinical and Biological Sciences, University of Turin, Italy
Study Director: Eric Baudin Oncologie Endocrinienne et Médecine Nucléaire, Institut Gustave Roussy, Villejuif, France.
Principal Investigator: Massimo Terzolo, MD Internal Medicine, Department of Clinical and Biological Sciences, University of Turin, Italy
Study Director: Sophie Leboulleux Service de Médecine Nucléaire et de Cancérologie Endocrinienne, Institut Gustave-
  More Information

Publications:
Responsible Party: Alfredo Berruti, Dipartimento di Scienze Cliniche e Biologiche Università di Torino
ClinicalTrials.gov Identifier: NCT00786110     History of Changes
Other Study ID Numbers: EudraCT 2008-000759-91
Study First Received: November 5, 2008
Last Updated: February 23, 2009
Health Authority: Italy: The Italian Medicines Agency

Keywords provided by University of Turin, Italy:
Sorafenib
Paclitaxel
Disease free survival

Additional relevant MeSH terms:
Adrenocortical Carcinoma
Carcinoma
Adenocarcinoma
Adrenal Cortex Diseases
Adrenal Cortex Neoplasms
Adrenal Gland Diseases
Adrenal Gland Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Paclitaxel
Sorafenib
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on October 22, 2014