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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Axelar AB
ClinicalTrials.gov Identifier:
NCT01561456
First received: March 5, 2012
Last updated: December 4, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Non-small-cell Lung Cancer
Squamous Cell Carcinoma
Adenocarcinoma of the Lung
Drug: AXL1717
Drug: Docetaxel
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Axelar AB:

Primary Outcome Measures:
  • Rate of progression-free survival (PFS) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Rate of complete response (CR), partial response (PR), stable disease, (SD), progressive disease (PD), disease control (CR + PR + SD), and objective response (CR + PR) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Median time to disease progression (TTP), time to objective response and time to treatment failure (TTF) [ Time Frame: 17 weeks ] [ Designated as safety issue: No ]
  • Median duration of progression-free-survival (PFS), objective response and disease control [ Time Frame: 17 weeks ] [ Designated as safety issue: No ]
  • 12-week survival [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • 1 year survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Investigational product toxicity profile [ Time Frame: 17 weeks ] [ Designated as safety issue: Yes ]
  • Overall survival [ Time Frame: time from randomization to death from any cause ] [ Designated as safety issue: No ]

Enrollment: 100
Study Start Date: December 2011
Study Completion Date: December 2013
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AXL1717
AXL1717
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
Other Name: small molecule IGF-1 inhibitor
Active Comparator: Docetaxel
Docetaxel
Drug: Docetaxel
Docetaxel administered as a standard treatment (75 mg/m2 IV infusion over 1 hour) once every three weeks throughout the 4-cycle study
Other Name: Taxotere

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01561456

Locations
Belarus
State Medical Institution: Republic Scientific Oncology Center
Poselok, Minsk Region, Belarus, 223040
Gomel Regional Clinical Oncology Center
Gomel, Belarus, 246012
Minsk City Clinical Oncology Center
Minsk, Belarus, 220013
Vitebsk Regional Clinical Oncology Center
Vitebsk, Belarus, 210603
Hungary
Semmelweis University; Clinic for Pulmonology
Budapest, Hungary, 1125
Kenezy Gyula County Hospital
Debrecen, Hungary, 4043
University of Debrecen Medical and Health Science Center, Clinic of Pulmonology
Debrecen, Hungary, 4042
Hospital for Thoracic Diseases of Csongrad County Local Government
Deszk, Hungary, 6772
Poland
Wladyslaw Bieganski Regional Specialist Hospital
Grudziadz, Poland, 86-300
Maria Sklodowska-Curie Institute of Oncology in Warsaw
Warsaw, Poland, 02781
Russian Federation
State Therapeutical and Prophylactic Institution: Chelyabinsk Regional Oncology Center
Chelyabinsk, Russian Federation, 454087
Sverdlovsk Regional Oncology Center
Ekaterinburg, Russian Federation, 620036
City Clinical Hospital #1
Novosibirsk, Russian Federation, 630047
Orel Oncology Center
Orel, Russian Federation, 302020
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, 197089
St. Petersburg State Medical Institution Municipal Clinical Oncology Center
St. Petersburg, Russian Federation, 197022
Tula Regional Oncology Center
Tula, Russian Federation, 300053
Ukraine
Dnipropetrovsk City Multispecialty Clinical Hospital #4
Dniepropetrovsk, Ukraine, 49102
Public Clinical Treatment and Prophylaxis Institution: Donetsk Regional Antitumor Center
Donetsk, Ukraine, 83092
Public Healthcare Institution: Kharkiv Regional Clinical Oncology Center
Kharkiv, Ukraine, 61070
Kharkiv, State Institution: S.P. Hryhoriev Institute of Medical Radiology under the Ukrainian Academy of Medical Sciences
Kharkiv, Ukraine, 61024
Kyiv City Oncology Hospital
Kyiv, Ukraine, 03115
Lviv State Regional Treatment and Diagnostics Oncology Center
Lviv, Ukraine, 79031
Zakarpattia Regional Clinical Oncology Center
Uzhhorod, Ukraine, 88014
Sponsors and Collaborators
Axelar AB
Investigators
Principal Investigator: Michael Bergqvist, MD, PhD Uppsala University Hospital, Sweden
  More Information

No publications provided

Responsible Party: Axelar AB
ClinicalTrials.gov Identifier: NCT01561456     History of Changes
Other Study ID Numbers: AXL-003, 2011-002007-15
Study First Received: March 5, 2012
Last Updated: December 4, 2013
Health Authority: Belarus: Ministry of Health
Hungary: Scientific and Medical Research Council Ethics Committee
Poland: The Central Register of Clinical Trials
Poland: Ethics Committee
Russia: Ministry of Health of the Russian Federation
Russia: Ethics Committee
Ukraine: Ministry of Health
Ukraine: Ethics Committee

Keywords provided by Axelar AB:
non-small-cell lung cancer
squamous cell carcinoma
adenocarcinoma of the lung
IGF-1 inhibitor
docetaxel
AXL1717
NSCLC
SCC
AC

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma
Carcinoma, Non-Small-Cell Lung
Carcinoma, Squamous Cell
Lung Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Neoplasms, Squamous Cell
Docetaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 26, 2014