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

Sponsor

Axelar AB (Industry)

Overall Status

Completed

CT.gov ID

NCT01561456

Collaborator

(none)

100

Enrollment

Locations

Arms

Duration (Months)

4.2

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

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

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (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

Study Start Date :

Dec 1, 2011

Actual Primary Completion Date :

Dec 1, 2013

Actual Study Completion Date :

Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
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 Names: 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 Names: Taxotere

Arm

Intervention/Treatment

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 Names:

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 Names:

Taxotere

Outcome Measures

Primary Outcome Measures

Rate of progression-free survival (PFS) [12 weeks]

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) [12 weeks]
Median time to disease progression (TTP), time to objective response and time to treatment failure (TTF) [17 weeks]
Median duration of progression-free-survival (PFS), objective response and disease control [17 weeks]
12-week survival [12 weeks]
1 year survival [1 year]
Investigational product toxicity profile [17 weeks]
Overall survival [time from randomization to death from any cause]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	State Medical Institution: Republic Scientific Oncology Center	Poselok	Minsk Region	Belarus	223040
2	Gomel Regional Clinical Oncology Center	Gomel		Belarus	246012
3	Minsk City Clinical Oncology Center	Minsk		Belarus	220013
4	Vitebsk Regional Clinical Oncology Center	Vitebsk		Belarus	210603
5	Semmelweis University; Clinic for Pulmonology	Budapest		Hungary	1125
6	University of Debrecen Medical and Health Science Center, Clinic of Pulmonology	Debrecen		Hungary	4042
7	Kenezy Gyula County Hospital	Debrecen		Hungary	4043
8	Hospital for Thoracic Diseases of Csongrad County Local Government	Deszk		Hungary	6772
9	Wladyslaw Bieganski Regional Specialist Hospital	Grudziadz		Poland	86-300
10	Maria Sklodowska-Curie Institute of Oncology in Warsaw	Warsaw		Poland	02781
11	State Therapeutical and Prophylactic Institution: Chelyabinsk Regional Oncology Center	Chelyabinsk		Russian Federation	454087
12	Sverdlovsk Regional Oncology Center	Ekaterinburg		Russian Federation	620036
13	City Clinical Hospital #1	Novosibirsk		Russian Federation	630047
14	Orel Oncology Center	Orel		Russian Federation	302020
15	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
16	St. Petersburg State Medical Institution Municipal Clinical Oncology Center	St. Petersburg		Russian Federation	197022
17	Tula Regional Oncology Center	Tula		Russian Federation	300053
18	Dnipropetrovsk City Multispecialty Clinical Hospital #4	Dniepropetrovsk		Ukraine	49102
19	Public Clinical Treatment and Prophylaxis Institution: Donetsk Regional Antitumor Center	Donetsk		Ukraine	83092
20	Kharkiv, State Institution: S.P. Hryhoriev Institute of Medical Radiology under the Ukrainian Academy of Medical Sciences	Kharkiv		Ukraine	61024
21	Public Healthcare Institution: Kharkiv Regional Clinical Oncology Center	Kharkiv		Ukraine	61070
22	Kyiv City Oncology Hospital	Kyiv		Ukraine	03115
23	Lviv State Regional Treatment and Diagnostics Oncology Center	Lviv		Ukraine	79031
24	Zakarpattia Regional Clinical Oncology Center	Uzhhorod		Ukraine	88014