Efficacy and Safety of Imatinib in Chordoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00150072
First received: September 7, 2005
Last updated: August 6, 2012
Last verified: August 2012
  Purpose

Preliminary response data, observed by Casali (Cancer, 2004) with imatinib 800 mg/day in patients affected by chordoma, need to be confirmed by a Phase II study, whose primary endpoint will be the formal assessment of clinical and pathological response. Aim of the study will be to explore treatment's activity, but also the potential impact of tumor response, the feasibility and outcome of subsequent surgery and radiotherapy. In addition, patterns of tumour response need to be investigated as well, given the peculiar patterns of response shown with molecular-targeted therapy in solid tumors.


Condition Intervention Phase
Chordoma
Drug: imatinib
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Imatinib Mesylate in Chordoma

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Tumor response [ Time Frame: Every 3 months for 2 years ] [ Designated as safety issue: No ]
    objective response according to RECIST and clinical response


Secondary Outcome Measures:
  • Overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    from the first day of sudy treatment to the day of death for any cause

  • Progression free survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    from the first day of sudy treatment to the day of death for any cause or documented progression

  • Safety and tolerability [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    frequency of adverse events, abnormal lab values, bone pain, use of analgesic medication

  • proportion of patients undergoing complete surgery [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    number of pts undergoing complete surgery vs the one of pts not amenable to complete surgery at enrolment


Enrollment: 55
Study Start Date: October 2004
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: imatinib Drug: imatinib

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histological diagnosis of chordoma.
  2. Biomolecular or immunohistochemical evidence of Imatinib mesylate target (PDGFRβ activation and/or presence of PDGFB). Biomolecular assessment of PDGFRβ activation should be made whenever possible. To this end, if frozen material is not available, obtaining of, fresh material is encouraged, if it should be obtained with no major distress for the patient, preferably through an incisional biopsy (to allow immunoprecipitation) or, if this is not feasible, a Trucut biopsy (to allow Western Blot assessment). However, if frozen or fresh material cannot be obtained, paraffined material is also acceptable.

    The biomolecular assessment will be centralized to the reference centers (to be defined).

  3. Measurable or evaluable disease
  4. Surgical resection of local disease unfeasible radically, or unaccepted by the patient, or amenable to become less demolitive, or easier, or likely more feasible, after cytoreduction, and/or metastatic disease. Debulking surgery before enrolment is allowed. In this case, enrolment should occur at least one month after surgery
  5. Performance status 0, 1, 2 or 3 (ECOG) (see § 8.1).
  6. Adequate end organ function, defined as the following: total bilirubin <1.5 x ULN, SGOT and SGPT <2.5 x UNL (or <5 x ULN if hepatic metastases are present), creatinine <1.5 x ULN.
  7. Adequate bone marrow function, defined as the following: ANC >1.5 x 10^9/L, platelets >100 x 10^9/L, Hb >9 g/dL. Blood transfusions are allowed to reach the baseline requested Hb level.
  8. Female patients of child-bearing potential must have negative pregnancy test within 7 days before initiation of study drug dosing. Post menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Male and female patients of reproductive potential must agree to employ an effective method of birth control throughout the study and for up to 3 months following discontinuation of study drug.
  9. Written, voluntary, informed consent.

Exclusion Criteria:

  1. Previous treatment with any other investigational or not investigational agents within 28 days of first day of study drug dosing.
  2. Other primary malignancy with <5 years clinically assessed disease-free interval, except basal cell skin cancer, cervical carcinoma in situ, or other neoplasms judged to entail a low risk of relapse.
  3. Grade III/IV cardiac problems as defined by the New York Heart Association Criteria (i.e., congestive heart failure, myocardial infarction within 6 months of study)
  4. Severe and/or uncontrolled medical disease (i.e., uncontrolled diabetes, chronic renal disease, or active uncontrolled infection).
  5. Known brain metastasis.
  6. Known chronic liver disease (i.e., chronic active hepatitis, and cirrhosis).
  7. Known diagnosis of human immunodeficiency virus (HIV) infection.
  8. Previous radiotherapy to >=25 % of the bone marrow.
  9. Major surgery within 2 weeks prior to study entry.
  10. Expected non-compliance to medical regimens.
  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: NCT00150072

Locations
Italy
Novartis Investigative Site
Aviano, Italy
Novartis Investigative Site
Bologna, Italy
Novartis Investigative Site
Candiolo, Italy
Novartis Investigative Site
Firenze, Italy
Novartis Investigative Site
Milano, Italy
Novartis Investigative Site
Napoli, Italy
Novartis Investigative Site
Padova, Italy
Novartis Investigative Site
Pisa, Italy
Novartis Investigative Site
Roma, Italy
Novartis Investigative Site
Rozzano, Italy
Novartis Investigative Site
Torino, Italy
Switzerland
Novartis Investigative Site
Lausanne, Switzerland
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00150072     History of Changes
Other Study ID Numbers: CSTI571BIT15
Study First Received: September 7, 2005
Last Updated: August 6, 2012
Health Authority: Italy: National Monitoring Centre for Clinical Trials - Ministry of Health

Keywords provided by Novartis:
chordoma
imatinib
PDGFR

Additional relevant MeSH terms:
Chordoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Imatinib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014