A Study of Ispinesib in Metastatic Breast Cancer

This study has been completed.
Sponsor:
Information provided by:
Cytokinetics
ClinicalTrials.gov Identifier:
NCT00607841
First received: January 22, 2008
Last updated: January 14, 2010
Last verified: January 2010
  Purpose

Phase I is a dose-escalation study designed to assess safety and tolerability in patients with metastatic breast cancer. Phase II will measure response rate in patients with metastatic breast cancer.


Condition Intervention Phase
Breast Neoplasms
Drug: Ispinesib (SB-715992)
Phase 1
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: A Phase I/II Non-Randomized, Open-Label, Dose-Finding Study of Ispinesib (SB-715992) Followed By a Fixed-Dose Study in Chemotherapy-Naïve Patients With Metastatic Breast Cancer (MBC).

Resource links provided by NLM:


Further study details as provided by Cytokinetics:

Primary Outcome Measures:
  • Safety and tolerability in patients with metastatic breast cancer. [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Assessment of response rate based on RECIST in patients with metastatic breast cancer [ Time Frame: 28 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: December 2007
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1

Phase I dose escalation to determine maximum tolerated dose (MTD).

Phase II using fixed dose determined in Phase I portion of study.

Drug: Ispinesib (SB-715992)
Phase I: Dose escalation of I.V. injection starting at 10mg/m2 on Days 1 and 15 of a 28 day cycle.
Drug: Ispinesib (SB-715992)
Phase II: Fixed dose to be determined based on Phase I findings on Days 1 and 15 of a 28 day cycle

Detailed Description:

The Phase I dose-escalation portion of the trial will determine the Dose Limiting Toxicities (DLT) and Maximum Tolerated Dose (MTD) of Ispinesib (SB-715992) monotherapy when administered as a one-hour infusion on Days 1 and 15 of a 28-day cycle in female patients with locally advanced or metastatic breast cancer. The Phase II regimen will evaluate the MTD determined in Phase I in chemotherapy-naïve female patients with measurable, locally advanced or metastatic breast cancer. Phase II will assess the overall response rate (ORR) derived from individual patient assessments of complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) based on RECIST, as determined by independent review.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically or cytologically confirmed locally advanced (Stage IIIb) or metastatic (Stage IV) adenocarcinoma of the breast. Staging is determined according to the American Joint Committee on Cancer, Cancer Staging Manual, Sixth Edition
  2. Has not received prior cytotoxic chemotherapy for breast cancer and is not currently receiving other anti-cancer therapy, including trastuzumab or other cytostatics, hormonal therapy, radiotherapy, immunotherapy, biologic or investigational agent(s).

    Note: Prior therapy does not include (a) previous surgery and/or radiotherapy (if less than 25% of pelvic bone marrow), (b) adjuvant and/or palliative hormonal therapy, (c) gefitinib (Iressa®) or trastuzumab (Herceptin®) given as monotherapy.

  3. Phase I only: Patients who have previously received anthracycline therapy in either the adjuvant or neoadjuvant setting may participate, provided a minimum of one year has elapsed since last treatment.
  4. Phase I only: Must have evaluable, but not necessarily measurable disease by imaging.
  5. Phase II only: Must have at least one unidimensionally measurable lesion evaluable by RECIST criteria. The lesion(s) must be documented by photography, radiography, direct measurement, or palpation.
  6. ECOG Performance Status of 0-1.
  7. Female patients, 18 years of age or older.
  8. A female is eligible to enter and participate in the study if she is of:

    1. Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who:

      • Has had a hysterectomy,
      • Has had a bilateral oophorectomy (ovariectomy),
      • Has had a bilateral tubal ligation, or
      • Is post-menopausal (a demonstration of total cessation of menses for ≥ 1 year.
    2. Childbearing potential, has a negative serum pregnancy test at screening, and agrees to one of the following:

      • Intrauterine Device (IUD),
      • Vasectomized partner who is sterile prior to the female patient's entry and is the sole sexual partner for that female,
      • Complete abstinence from sexual intercourse for two weeks before exposure to investigational product, throughout the clinical trial, and for at least one week after the last dose of investigational product, or
      • Double barrier contraception (condom with spermicidal jelly, foam, suppository, or film, diaphragm with spermicide, or male condom and diaphragm).
      • Progesterone based contraceptive with a failure rate of < 1%.
  9. A signed and dated written informed consent is obtained from the patient or the patient's legally acceptable representative prior to screening.

Exclusion Criteria:

  1. Receipt of prior cytotoxic chemotherapy except in an adjuvant or neo adjuvant setting
  2. Has not recovered from prior therapy including any major surgery, radiotherapy, immunotherapy, biologic or investigational agent(s).
  3. Absolute neutrophil count (ANC) <1,500/mm3.
  4. Platelets < 100,000/mm3.
  5. Creatinine clearance ≤ 40 mL/min as calculated by the Cockcroft-Gault Formula.
  6. Total bilirubin greater than or equal to 1.5 x ULN
  7. Alanine aminotransferase (ALT) greater than 2 times the upper limit of normal (ULN) in the absence of liver metastases (patients with serum transaminase levels up to 5 times ULN in the presence of liver metastases may be enrolled following approval by Cytokinetics Medical Monitor).
  8. Alkaline Phosphate (ALP) greater than or equal to 5 x ULN
  9. Female patients who are pregnant or lactating.
  10. Women of reproductive potential who do not agree to use an effective contraceptive method.
  11. Any unstable, pre-existing major medical condition or history of other malignancies (except excised cervical or basal skin/squamous cell carcinoma).
  12. Psychological, familial, sociological or geographical conditions that do not permit compliance with the study protocol.
  13. Evidence of central nervous system (CNS) metastases or leptomeningeal disease
  14. Evidence of any other malignancy
  15. Previous exposure to any Investigational Agent
  16. Radiation therapy within 28 days, or within 3 months if BUN is ≥20mg/dl
  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: NCT00607841

Locations
Peru
Instituto Nacional de Enfermedades Neoplásicas
Lima, Peru
Hospital Nacional Edgardo Rebagliati Martins
Lima, Peru
Hospital Nacional Alberto Sabogal Sologúren
Lima, Peru
Sponsors and Collaborators
Cytokinetics
  More Information

No publications provided

Responsible Party: Andrew Wolff, M.D., F.A.C.C., Chief Medical Officer, Cytokinetics, Inc.
ClinicalTrials.gov Identifier: NCT00607841     History of Changes
Other Study ID Numbers: CY 3121
Study First Received: January 22, 2008
Last Updated: January 14, 2010
Health Authority: Peru: Ministry of Health
United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases

ClinicalTrials.gov processed this record on July 29, 2014