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

Phase 2

Completed

• Conditions: Small Cell Lung Carcinoma
• Interventions: Drug: Amuvatinib

• Registration Number: NCT01357395
• Lead Sponsor: Astex Pharmaceuticals, Inc.

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.

Study Timeline

• Study Start: 2011-05
• Study First Submitted: 2011-05-17
• Study First Submitted QC: 2011-05-18
• Study First Posted: 2011-05-20
• Primary Completion: 2012-05
• Study Completion: 2012-05-28
• Disposition First Submitted: 2017-10-20
• Disposition First Submitted QC: 2017-10-20
• Disposition First Posted: 2017-10-24
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-01
• Last Update Posted: 2024-08-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 23

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Overall objective response rate (CR or PR)	3 months

Secondary Outcome Measures

Name	Time	Method
Progression-free survival and overall survival	6 months
Duration of response	6 months
Amuvatinib and metabolites PK and other biomarkers	6 months
Amuvatinib PK interactions with platinum-etoposide chemotherapy	6 months
Disease control rate	6 months
Safety and tolerability	6 months

Trial Locations

Locations (12)

Wojewódzki Szpital Specjalistyczny; 🇵🇱 Radom, Mazowieckie, Poland

Winship Cancer Institute of Emory University; 🇺🇸 Atlanta, Georgia, United States

Vanderbilt - Ingram Cancer Center; 🇺🇸 Nashville, Tennessee, United States

Associates in Oncology and Hematology; 🇺🇸 Chattanooga, Tennessee, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Wojewódzki Szpital im. Św. Ojca Pio w Przemyślu Oddział Onkologiczny z Pododdziałem Dziennej Chemioterapii; 🇵🇱 Przemyśl, Podkarpackie, Poland

Specjalistyczny Szpital im. Alfreda Sokolowskiego; 🇵🇱 Szczecin, Zachodniopomorskie, Poland

Wojewódzkie Centrum Onkologii; 🇵🇱 Gdansk, Pomorskie, Poland

Centrum Onkologii - Instytut im. M. Sklodowskiej-Curie w Warszawie; 🇵🇱 Warszawa, Mazowieckie, Poland

University of Colorado Cancer Center; 🇺🇸 Aurora, Colorado, United States

James Graham Brown Cancer Center, University of Louisville; 🇺🇸 Louisville, Kentucky, United States

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States