Study of AXL1717 Compared to Docetaxel to Treat Squamous Cell Carcinoma or Adenocarcinoma of the Lung

Squamous Cell Carcinoma Clinical Trial

Official title:

Phase II, Randomized, Open-label Study of the IGF-1R Inhibitor AXL1717 Compared to Docetaxel in Patients With Previously Treated, Locally Advanced, or Metastatic Squamous Cell Carcinoma or Adenocarcinoma of the Lung

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01561456
• Other study ID #: AXL-003
• Secondary ID: 2011-002007-15
• Status: Completed
• Phase: Phase 2
• First received: March 5, 2012
• Last updated: December 4, 2013
• Start date: December 2011
• Est. completion date: December 2013

Study information

• Verified date: December 2013
• Source: Axelar AB
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belarus: Ministry of HealthHungary: Scientific and Medical Research Council Ethics CommitteePoland: The Central Register of Clinical TrialsPoland: Ethics CommitteeRussia: Ministry of Health of the Russian FederationRussia: Ethics CommitteeUkraine: Ministry of HealthUkraine: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare effectiveness and safety of experimental anticancer medicine, AXL1717, and docetaxel in patients with squamous cell carcinoma or adenocarcinoma of the lung.

Description:

Non-Small-Cell lung Cancer (NSCLC) is the most common form of lung cancer, and treatment with cytotoxic chemotherapy only provides a 10% reduction in the risk of death in patients with advanced NSCLC. One-third of all non-resectable advanced NSCLC patients in second line do not receive chemotherapy treatment at all. In the absence of treatment the Progression-Free Survival (PFS) for NSCLC patients is dismal, in the range of 6-8 weeks, and treatment only modestly improves the median PFS to 10-11 weeks. Therefore, because of an overall poorer prognosis for patients with advanced NSCLC, development of new agents is urgently needed.

AXL1717 is a small molecule experimental product developed by Axelar AB as anticancer agent for oral administration. AXL1717 inhibits the insulin-like growth factor 1 (IGF-1), which is often over expressed in lung tumors and can mediate the proliferation of lung cancer cells and resistance to therapy. Results of previous preclinical and clinical studies indicate that AXL1717 will be tolerable and effective in patients with previously-treated, advanced squamous cell carcinoma (SCC) and adenocarcinoma (AC) histological subtypes of NSCLC.

This is an open label, randomized, multi-center, Phase II study to investigate AXL1717 compared to docetaxel in patients with squamous cell carcinoma (SCC) or adenocarcinoma (AC) of the lung. Patients with previously treated, locally advanced or metastatic SCC or AC subtypes of NSCLC in need of additional treatment will be enrolled in the study. Patients will be randomized to either AXL1717 or to docetaxel group as monotherapy, in a 3:2 ratio for each NSCLC subtype. Patients in AXL1717 group will receive 400 mg AXL1717 twice daily (BID) as oral suspension for 21 days per cycle; i.e. daily for up to four cycles unless a dose interruption, delay, or reduction is required. Docetaxel will be administered as a standard treatment (75 mg/m2 IV infusion over 1 hour) once every three weeks throughout the 4-cycle study. The primary objective of the study is to compare the rate of progression-free survival (PFS) at 12 weeks between patients treated with AXL1717 and patients treated with docetaxel. Additional efficacy and safety parameters will be monitored throughout the study. Patients treated with AXL1717 who are responding to treatment or remain stable at the end of 4 cycles may be offered an extension of treatment with AXL1717.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• informed of the study and have provided written informed consent

• At least 18 years of age

• Histologically confirmed diagnosis of locally advanced, or metastatic squamous cell carcinoma or adenocarcinoma histological subtypes of non-small-cell lung cancer (stage IIIB or IV)

• For patients with squamous cell histology: previously treated with first-line chemotherapy and has had disease progression during or after first-line therapy.

• For patients with adenocarcinoma histology: previously treated with one or two lines of chemotherapy.

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2

• Life expectancy = 3 months

• Measurable disease by RECIST 1.1 criteria

• Hematology values: blood leukocyte count = 3.0 x 109/L, blood absolute neutrophil count = 1.5 x 109/L, blood platelet count = 100 x109/L, hemoglobin = 100 g/L (transfusions are allowed)

• Clinical chemistry values: plasma total bilirubin level = upper limit of the "normal" range (ULN; i.e. reference), plasma AST or ALT = 1.5 x ULN (= 5 times if liver metastases have been documented) and plasma creatinine = 2.0 x ULN

• 12-lead ECG with normal tracings

Exclusion Criteria:

• Mixed histology of squamous and non-squamous NSCLC

• Ongoing infection or other major recent or ongoing disease that, according to the Investigator, poses an unacceptable risk to the patient

• Known primary or secondary central nervous system malignancy.

• Active or previously treated carcinomatous meningitis

• Truly non-measurable disease by RECIST 1.1 criteria, such as patients with one or more of the following without any RECIST measurable disease:

• Bone lesions

• Ascites

• Pleural or pericardial effusion

• Lymphangitis cutis or pulmonis

• Cystic lesions

• Grade 3 or higher constipation within the past 28 days or grade 2 constipation within the past 14 days before randomization.

• Active hepatitis B, active hepatitis C, or known HIV infection

• Coexisting uncontrolled medical condition, including active cardiac disease (such as unstable angina, myocardial infarction within 6 months, or New York Heart Association Class III/IV congestive heart failure), and significant dementia

• Hepatic impairment as indicated by abnormalities of transaminases (AST and/or ALT > 1.5 × ULN or AST and/or ALT > 5 times ULN if liver metastases have been documented) and/or increased alkaline phosphatase (> 2.5 × ULN) considered as a result of hepatic impairment (and not from bone disease)

• History of cancer that has required treatment or been active within the past 5 years, other than NSCLC, basal cell carcinoma, or cervical carcinoma in situ

• Major surgical procedure within 4 weeks prior to randomization

• More than one prior anti-tumor systemic therapy for advanced squamous cell NSCLC, and more than two prior lines of chemotherapy for advanced adenocarcinoma NSCLC

• Previous use of docetaxel in any line of therapy

• Women of child bearing potential (WOCBP) who do not consent to using acceptable methods of contraception

• Women who are breast-feeding or have a positive pregnancy test at screening

• Current participation in any other investigational clinical trial or any administration of an investigational agent within 4 weeks of study drug administration

• ECOG performance status > 2

• Life expectancy < 3 months

• Known or suspected hypersensitivity to AXL1717 or docetaxel or to drugs formulated with polysorbate 80

• Lack of suitability for participation in the trial, for any reason, as judged by the Investigator

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of the Lung
• Carcinoma
• Carcinoma, Non-Small-Cell Lung
• Carcinoma, Squamous Cell
• Lung Neoplasms
• Non-small-cell Lung Cancer
• Squamous Cell Carcinoma

Intervention

Drug:
• AXL1717
AXL1717 administered as oral suspension at 400 mg twice daily for 21 days per cycle; i.e. daily for up to four cycles
• Docetaxel
Docetaxel administered as a standard treatment (75 mg/m2 IV infusion over 1 hour) once every three weeks throughout the 4-cycle study

Locations

Country	Name	City	State
Belarus	Gomel Regional Clinical Oncology Center	Gomel
Belarus	Minsk City Clinical Oncology Center	Minsk
Belarus	State Medical Institution: Republic Scientific Oncology Center	Poselok	Minsk Region
Belarus	Vitebsk Regional Clinical Oncology Center	Vitebsk
Hungary	Semmelweis University; Clinic for Pulmonology	Budapest
Hungary	Kenezy Gyula County Hospital	Debrecen
Hungary	University of Debrecen Medical and Health Science Center, Clinic of Pulmonology	Debrecen
Hungary	Hospital for Thoracic Diseases of Csongrad County Local Government	Deszk
Poland	Wladyslaw Bieganski Regional Specialist Hospital	Grudziadz
Poland	Maria Sklodowska-Curie Institute of Oncology in Warsaw	Warsaw
Russian Federation	State Therapeutical and Prophylactic Institution: Chelyabinsk Regional Oncology Center	Chelyabinsk
Russian Federation	Sverdlovsk Regional Oncology Center	Ekaterinburg
Russian Federation	City Clinical Hospital #1	Novosibirsk
Russian Federation	Orel Oncology Center	Orel
Russian Federation	State Higher Educational Institution St. Petersburg State Medical University n. a. after I. P. Pavlov under Federal Agency for Healthcare and Social Development, Research Institute of Pulmonology	Saint Petersburg
Russian Federation	St. Petersburg State Medical Institution Municipal Clinical Oncology Center	St. Petersburg
Russian Federation	Tula Regional Oncology Center	Tula
Ukraine	Dnipropetrovsk City Multispecialty Clinical Hospital #4	Dniepropetrovsk
Ukraine	Public Clinical Treatment and Prophylaxis Institution: Donetsk Regional Antitumor Center	Donetsk
Ukraine	Kharkiv, State Institution: S.P. Hryhoriev Institute of Medical Radiology under the Ukrainian Academy of Medical Sciences	Kharkiv
Ukraine	Public Healthcare Institution: Kharkiv Regional Clinical Oncology Center	Kharkiv
Ukraine	Kyiv City Oncology Hospital	Kyiv
Ukraine	Lviv State Regional Treatment and Diagnostics Oncology Center	Lviv
Ukraine	Zakarpattia Regional Clinical Oncology Center	Uzhhorod

Sponsors (1)

Lead Sponsor	Collaborator
Axelar AB

Countries where clinical trial is conducted

Belarus,  Hungary,  Poland,  Russian Federation,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of progression-free survival (PFS)		12 weeks	No
Secondary	Rate of complete response (CR), partial response (PR), stable disease, (SD), progressive disease (PD), disease control (CR + PR + SD), and objective response (CR + PR)		12 weeks	No
Secondary	Median time to disease progression (TTP), time to objective response and time to treatment failure (TTF)		17 weeks	No
Secondary	Median duration of progression-free-survival (PFS), objective response and disease control		17 weeks	No
Secondary	12-week survival		12 weeks	No
Secondary	1 year survival		1 year	No
Secondary	Investigational product toxicity profile		17 weeks	Yes
Secondary	Overall survival		time from randomization to death from any cause	No