Back to resultsA Phase 2, Open-Label Study of Amuvatinib in Combination With Platinum-Etoposide Chemotherapy in Small Cell Lung Cancer (ESCAPE)
Primary Purpose
Small Cell Lung Carcinoma
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Amuvatinib
Sponsored by
About this trial
This is an interventional treatment trial for Small Cell Lung Carcinoma focused on measuring Small Cell Lung Carcinoma
Eligibility Criteria
Inclusion Criteria:
- Male or female ≥ 18 of age at the time of consent and have histologically or cytologically confirmed SCLC
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
- 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
- ECOG performance status 0 to 2
- Adequate organ function
- 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.
- Sign approved informed consent form
Exclusion Criteria:
- Prior exposure to amuvatinib
- 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
- 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
- Mixed SCLC and non-small cell lung cancer, or large cell lung cancer
- Untreated, unstable, or symptomatic brain metastasis
- Hypersensitivity to amuvatinib, excipients of amuvatinib, or any agent given in association with this trial
- 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
Sites / Locations
- University of Colorado Cancer Center
- Winship Cancer Institute of Emory University
- James Graham Brown Cancer Center, University of Louisville
- Washington University School of Medicine
- Associates in Oncology and Hematology
- Vanderbilt - Ingram Cancer Center
- MD Anderson Cancer Center
- Wojewódzki Szpital Specjalistyczny
- Centrum Onkologii - Instytut im. M. Sklodowskiej-Curie w Warszawie
- Wojewódzki Szpital im. Św. Ojca Pio w Przemyślu Oddział Onkologiczny z Pododdziałem Dziennej Chemioterapii
- Wojewódzkie Centrum Onkologii
- Specjalistyczny Szpital im. Alfreda Sokolowskiego
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Amuvatinib
Arm Description
Amuvatinib 300 mg PO TID + standard-of-care platinum-etoposide
Outcomes
Primary Outcome Measures
Overall objective response rate (CR or PR)
Secondary Outcome Measures
Progression-free survival and overall survival
Disease control rate
Duration of response
Safety and tolerability
Amuvatinib and metabolites PK and other biomarkers
Amuvatinib PK interactions with platinum-etoposide chemotherapy
Full Information
NCT ID
NCT01357395
First Posted
May 17, 2011
Last Updated
October 20, 2017
Sponsor
Astex Pharmaceuticals, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT01357395
Brief Title
A Phase 2, Open-Label Study of Amuvatinib in Combination With Platinum-Etoposide Chemotherapy in Small Cell Lung Cancer
Acronym
ESCAPE
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 Type
Interventional
2. Study Status
Record Verification Date
October 2017
Overall Recruitment Status
Completed
Study Start Date
May 2011 (undefined)
Primary Completion Date
May 2012 (Actual)
Study Completion Date
May 28, 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Astex Pharmaceuticals, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Small Cell Lung Carcinoma
Keywords
Small Cell Lung Carcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
23 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Amuvatinib
Arm Type
Experimental
Arm Description
Amuvatinib 300 mg PO TID + standard-of-care platinum-etoposide
Intervention Type
Drug
Intervention Name(s)
Amuvatinib
Other Intervention Name(s)
MP-470
Intervention Description
Amuvatinib 300 mg PO TID
Primary Outcome Measure Information:
Title
Overall objective response rate (CR or PR)
Time Frame
3 months
Secondary Outcome Measure Information:
Title
Progression-free survival and overall survival
Time Frame
6 months
Title
Disease control rate
Time Frame
6 months
Title
Duration of response
Time Frame
6 months
Title
Safety and tolerability
Time Frame
6 months
Title
Amuvatinib and metabolites PK and other biomarkers
Time Frame
6 months
Title
Amuvatinib PK interactions with platinum-etoposide chemotherapy
Time Frame
6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female ≥ 18 of age at the time of consent and have histologically or cytologically confirmed SCLC
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
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
ECOG performance status 0 to 2
Adequate organ function
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.
Sign approved informed consent form
Exclusion Criteria:
Prior exposure to amuvatinib
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
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
Mixed SCLC and non-small cell lung cancer, or large cell lung cancer
Untreated, unstable, or symptomatic brain metastasis
Hypersensitivity to amuvatinib, excipients of amuvatinib, or any agent given in association with this trial
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
Facility Information:
Facility Name
University of Colorado Cancer Center
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Winship Cancer Institute of Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
James Graham Brown Cancer Center, University of Louisville
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63108
Country
United States
Facility Name
Associates in Oncology and Hematology
City
Chattanooga
State/Province
Tennessee
ZIP/Postal Code
37404
Country
United States
Facility Name
Vanderbilt - Ingram Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Wojewódzki Szpital Specjalistyczny
City
Radom
State/Province
Mazowieckie
ZIP/Postal Code
26-617
Country
Poland
Facility Name
Centrum Onkologii - Instytut im. M. Sklodowskiej-Curie w Warszawie
City
Warszawa
State/Province
Mazowieckie
ZIP/Postal Code
02-781
Country
Poland
Facility Name
Wojewódzki Szpital im. Św. Ojca Pio w Przemyślu Oddział Onkologiczny z Pododdziałem Dziennej Chemioterapii
City
Przemyśl
State/Province
Podkarpackie
ZIP/Postal Code
37-700
Country
Poland
Facility Name
Wojewódzkie Centrum Onkologii
City
Gdansk
State/Province
Pomorskie
ZIP/Postal Code
80-219
Country
Poland
Facility Name
Specjalistyczny Szpital im. Alfreda Sokolowskiego
City
Szczecin
State/Province
Zachodniopomorskie
ZIP/Postal Code
70-891
Country
Poland
12. IPD Sharing Statement
Learn more about this trial
A Phase 2, Open-Label Study of Amuvatinib in Combination With Platinum-Etoposide Chemotherapy in Small Cell Lung Cancer
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