Clinical trial NCT01357395: A Phase 2, Open-Label Study of Amuvatinib in Combination With Platinum-Etoposide Chemotherapy in Small Cell Lung Cancer
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Small Cell Lung Carcinoma
Keywords: Small Cell Lung Carcinoma
Lead sponsor: Astex Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2011-05-20
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Overall objective response rate (CR or PR)
timeFrame: 3 months
Secondary outcomes:
measure: Progression-free survival and overall survival
timeFrame: 6 months
measure: Disease control rate
timeFrame: 6 months
measure: Duration of response
timeFrame: 6 months
measure: Safety and tolerability
timeFrame: 6 months
measure: Amuvatinib and metabolites PK and other biomarkers
timeFrame: 6 months
measure: Amuvatinib PK interactions with platinum-etoposide chemotherapy
timeFrame: 6 months
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Louisville
country: United States
facility: James Graham Brown Cancer Center, University of Louisville
state: Kentucky
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Chattanooga
country: United States
facility: Associates in Oncology and Hematology
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt - Ingram Cancer Center
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Radom
country: Poland
facility: Wojewódzki Szpital Specjalistyczny
state: Mazowieckie
city: Warszawa
country: Poland
facility: Centrum Onkologii - Instytut im. M. Sklodowskiej-Curie w Warszawie
state: Mazowieckie
city: Przemyśl
country: Poland
facility: Wojewódzki Szpital im. Św. Ojca Pio w Przemyślu Oddział Onkologiczny z Pododdziałem Dziennej Chemioterapii
state: Podkarpackie
city: Gdansk
country: Poland
facility: Wojewódzkie Centrum Onkologii
state: Pomorskie
city: Szczecin
country: Poland
facility: Specjalistyczny Szpital im. Alfreda Sokolowskiego
state: Zachodniopomorskie
Study officials:
References: