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
Overview
- Phase
- Phase 2
- Intervention
- AXL1717
- Conditions
- Non-small-cell Lung Cancer
- Sponsor
- Axelar AB
- Enrollment
- 100
- Locations
- 24
- Primary Endpoint
- Rate of progression-free survival (PFS)
- Status
- Completed
- Last Updated
- 12 years ago
Overview
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.
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.
Investigators
Eligibility 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
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
- •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.
Arms & Interventions
AXL1717
AXL1717
Intervention: AXL1717
Docetaxel
Docetaxel
Intervention: Docetaxel
Outcomes
Primary Outcomes
Rate of progression-free survival (PFS)
Time Frame: 12 weeks
Secondary Outcomes
- 1 year survival(1 year)
- Investigational product toxicity profile(17 weeks)
- 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)
- Overall survival(time from randomization to death from any cause)