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

NCT ID: NCT01357395

Last Updated: 2024-08-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-05-31
• Study Completion Date: 2012-05-28

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.

Conditions

Small Cell Lung Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Amuvatinib

Amuvatinib 300 mg PO TID + standard-of-care platinum-etoposide

Group Type: EXPERIMENTAL

Amuvatinib

Intervention Type: DRUG

Amuvatinib 300 mg PO TID

Interventions

Amuvatinib

Amuvatinib 300 mg PO TID

Intervention Type: DRUG

Other Intervention Names

MP-470

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Astex Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Colorado Cancer Center

Aurora, Colorado, United States

Winship Cancer Institute of Emory University

Atlanta, Georgia, United States

James Graham Brown Cancer Center, University of Louisville

Louisville, Kentucky, United States

Washington University School of Medicine

St Louis, Missouri, United States

Associates in Oncology and Hematology

Chattanooga, Tennessee, United States

Vanderbilt - Ingram Cancer Center

Nashville, Tennessee, United States

MD Anderson Cancer Center

Houston, Texas, United States

Wojewódzki Szpital Specjalistyczny

Radom, Masovian Voivodeship, Poland

Centrum Onkologii - Instytut im. M. Sklodowskiej-Curie w Warszawie

Warsaw, Masovian Voivodeship, Poland

Wojewódzki Szpital im. Św. Ojca Pio w Przemyślu Oddział Onkologiczny z Pododdziałem Dziennej Chemioterapii

Przemyśl, Podkarpackie Voivodeship, Poland

Wojewódzkie Centrum Onkologii

Gdansk, Pomeranian Voivodeship, Poland

Specjalistyczny Szpital im. Alfreda Sokolowskiego

Szczecin, West Pomeranian Voivodeship, Poland

Countries

United States; Poland

Other Identifiers

2010-024378-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

SGI-0470-07

Identifier Type: -

Identifier Source: org_study_id