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

Small Cell Lung Carcinoma Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01357395
• Other study ID #: SGI-0470-07
• Secondary ID: 2010-024378-21
• Status: Completed
• Phase: Phase 2
• First received: May 17, 2011
• Last updated: October 20, 2017
• Start date: May 2011
• Est. completion date: May 28, 2012

Study information

• Verified date: October 2017
• Source: Astex Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: May 28, 2012
• Est. primary completion date: May 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lung Neoplasms
• Small Cell Lung Carcinoma

Intervention

Drug:
• Amuvatinib
Amuvatinib 300 mg PO TID

Locations

Country	Name	City	State
Poland	Wojewódzkie Centrum Onkologii	Gdansk	Pomorskie
Poland	Wojewódzki Szpital im. Sw. Ojca Pio w Przemyslu Oddzial Onkologiczny z Pododdzialem Dziennej Chemioterapii	Przemysl	Podkarpackie
Poland	Wojewódzki Szpital Specjalistyczny	Radom	Mazowieckie
Poland	Specjalistyczny Szpital im. Alfreda Sokolowskiego	Szczecin	Zachodniopomorskie
Poland	Centrum Onkologii - Instytut im. M. Sklodowskiej-Curie w Warszawie	Warszawa	Mazowieckie
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	University of Colorado Cancer Center	Aurora	Colorado
United States	Associates in Oncology and Hematology	Chattanooga	Tennessee
United States	MD Anderson Cancer Center	Houston	Texas
United States	James Graham Brown Cancer Center, University of Louisville	Louisville	Kentucky
United States	Vanderbilt - Ingram Cancer Center	Nashville	Tennessee
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Astex Pharmaceuticals

Countries where clinical trial is conducted

United States,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall objective response rate (CR or PR)		3 months
Secondary	Progression-free survival and overall survival		6 months
Secondary	Disease control rate		6 months
Secondary	Duration of response		6 months
Secondary	Safety and tolerability		6 months
Secondary	Amuvatinib and metabolites PK and other biomarkers		6 months
Secondary	Amuvatinib PK interactions with platinum-etoposide chemotherapy		6 months