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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01357395
Recruitment Status : Completed
First Posted : May 20, 2011
Last Update Posted : October 24, 2017
Information provided by (Responsible Party):
Astex Pharmaceuticals

Brief Summary:
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 or disease Intervention/treatment Phase
Small Cell Lung Carcinoma Drug: Amuvatinib Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 23 participants
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : May 2011
Actual Primary Completion Date : May 2012
Actual Study Completion Date : May 28, 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Amuvatinib
Amuvatinib 300 mg PO TID + standard-of-care platinum-etoposide
Drug: Amuvatinib
Amuvatinib 300 mg PO TID
Other Name: MP-470

Primary Outcome Measures :
  1. Overall objective response rate (CR or PR) [ Time Frame: 3 months ]

Secondary Outcome Measures :
  1. Progression-free survival and overall survival [ Time Frame: 6 months ]
  2. Disease control rate [ Time Frame: 6 months ]
  3. Duration of response [ Time Frame: 6 months ]
  4. Safety and tolerability [ Time Frame: 6 months ]
  5. Amuvatinib and metabolites PK and other biomarkers [ Time Frame: 6 months ]
  6. Amuvatinib PK interactions with platinum-etoposide chemotherapy [ Time Frame: 6 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01357395

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
Saint 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
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

Responsible Party: Astex Pharmaceuticals Identifier: NCT01357395     History of Changes
Other Study ID Numbers: SGI-0470-07
2010-024378-21 ( EudraCT Number )
First Posted: May 20, 2011    Key Record Dates
Last Update Posted: October 24, 2017
Last Verified: October 2017

Keywords provided by Astex Pharmaceuticals:
Small Cell Lung Carcinoma

Additional relevant MeSH terms:
Small Cell Lung Carcinoma
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Etoposide phosphate
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action