A Phase 2, Open-Label Study of Amuvatinib in Combination With Platinum-Etoposide Chemotherapy in Small Cell Lung Cancer (ESCAPE)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2012 by Astex Pharmaceuticals.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by (Responsible Party):
Astex Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01357395
First received: May 17, 2011
Last updated: October 17, 2012
Last verified: September 2012
  Purpose

The purpose of the study is to evaluate the safety and potential benefit of combination amuvatinib with standard of care chemotherapy treatment (platinum and etoposide) in small cell lung cancer (SCLC) subjects.


Condition Intervention Phase
Small Cell Lung Carcinoma
Drug: Amuvatinib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2, Open-Label, Multi-Center Study of Amuvatinib in Combination With Platinum-Etoposide Chemotherapy in Small Cell Lung Cancer Subjects Who Have Not Responded to Standard Treatment or Relapsed After Standard Treatment

Resource links provided by NLM:


Further study details as provided by Astex Pharmaceuticals:

Primary Outcome Measures:
  • Overall objective response rate (CR or PR) [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-free survival and overall survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Disease control rate [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Duration of response [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Safety and tolerability [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Amuvatinib and metabolites PK and other biomarkers [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Amuvatinib PK interactions with platinum-etoposide chemotherapy [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: May 2011
Estimated Study Completion Date: May 2013
Estimated Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Amuvatinib
Amuvatinib 300 mg PO TID + standard-of-care platinum-etoposide
Drug: Amuvatinib
Amuvatinib 300 mg PO TID
Other Name: MP-470

Detailed Description:

Amuvatinib is an oral multi-targeted tyrosine kinase inhibitor which inhibits the mutant forms of c-Kit and PDGFR alpha. It also disrupts DNA repair likely through suppression of Homologous Recombination protein Rad51. In a Phase 1b clinical study in combination with VP-16 and carboplatin, responses in SCLC were observed. In vitro and in vivo data demonstrated amuvatinib synergy with VP-16 thereby further supporting this combination for continued evaluation in clinical trials. Pharmacokinetic data from Phase 1 clinical trials suggest that co-administration of amuvatinib did not alter exposures of standard of care agents VP-16 or carboplatin as measured by overall exposure.

  Eligibility

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

Inclusion Criteria:

  1. Male or female ≥ 18 of age at the time of consent and have histologically or cytologically confirmed SCLC
  2. Measurable SCLC per RECIST guideline that meets one of the following:

    • Disease progression by RECIST at anytime during platinum-etoposide (PE) chemotherapy;
    • Relapse by RECIST within 90 days after completing PE chemotherapy;
    • Stable disease by RECIST as best response after at least two (2) ≥ 21-day cycles of PE chemotherapy. The assessment of stable disease should be made at least 2 weeks after the start of the second cycle

    Subjects who received another second-line therapy are eligible if they still fulfill any one of the above three conditions, and all other eligibility criteria

  3. Start treatment with the same last regimen (dose and schedule) of first-line PE chemotherapy that they progressed or relapsed on, including any dose reductions because of toxicity, prior to study entry
  4. ECOG performance status 0 to 2
  5. Adequate organ function
  6. Subjects with screening 12-lead ECG with measurable QTc interval of < 450 msec. If QTc ≥ 450 msec, then confirm the reading by evaluating the mean QTc interval of triplicate ECGs.
  7. Sign approved informed consent form

Exclusion Criteria:

  1. Prior exposure to amuvatinib
  2. No longer eligible for first-line PE chemotherapy due to toxicity and the Investigator believes that the risk of retreating with the same PE chemotherapy regimen would outweigh the benefit
  3. Ongoing toxicity from prior treatment unless the toxicity has resolved, or in the opinion of the Investigator, is stable and does not compromise the safety of the subject
  4. Mixed SCLC and non-small cell lung cancer, or large cell lung cancer
  5. Untreated, unstable, or symptomatic brain metastasis
  6. Hypersensitivity to amuvatinib, excipients of amuvatinib, or any agent given in association with this trial
  7. A life-threatening illness, medical condition or organ system dysfunction which, in the Investigator's opinion, could compromise the subject's safety or interfere with study outcomes
  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: NCT01357395

Locations
United States, Colorado
University of Colorado Cancer Center
Aurora, Colorado, United States, 80045
United States, Georgia
Winship Cancer Institute of Emory University
Atlanta, Georgia, United States, 30322
United States, Kentucky
James Graham Brown Cancer Center, University of Louisville
Louisville, Kentucky, United States, 40202
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63108
United States, Tennessee
Associates in Oncology and Hematology
Chattanooga, Tennessee, United States, 37404
Vanderbilt - Ingram Cancer Center
Nashville, Tennessee, United States, 37232
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
Poland
Wojewódzki Szpital Specjalistyczny
Radom, Mazowieckie, Poland, 26-617
Centrum Onkologii - Instytut im. M. Sklodowskiej-Curie w Warszawie
Warszawa, Mazowieckie, Poland, 02-781
Wojewódzki Szpital im. Św. Ojca Pio w Przemyślu Oddział Onkologiczny z Pododdziałem Dziennej Chemioterapii
Przemyśl, Podkarpackie, Poland, 37-700
Wojewódzkie Centrum Onkologii
Gdansk, Pomorskie, Poland, 80-219
Specjalistyczny Szpital im. Alfreda Sokolowskiego
Szczecin, Zachodniopomorskie, Poland, 70-891
Sponsors and Collaborators
Astex Pharmaceuticals
  More Information

No publications provided

Responsible Party: Astex Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01357395     History of Changes
Other Study ID Numbers: SGI-0470-07, 2010-024378-21
Study First Received: May 17, 2011
Last Updated: October 17, 2012
Health Authority: United States: Food and Drug Administration
Poland: Ministry of Health

Keywords provided by Astex Pharmaceuticals:
Small Cell Lung Carcinoma

Additional relevant MeSH terms:
Carcinoma
Small Cell Lung Carcinoma
Lung Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Etoposide
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014