A Phase 1/2 Study of the Oral ALK/EGFR Inhibitor AP26113

Phase 1

• Conditions: Dose Escalation Phase: Histologically confirmed advanced malignancies. All histologies except leukaemia. Dose Expansion Phase: Non-small cell lung cancer (NSCLC); MedDRA version: 14.1Level: HLTClassification code 10029105Term: Neoplasms malignant site unspecified NECSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.1Level: LLTClassification code 10048683Term: Advanced cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.1Level: SOCClassification code 10029104Term: Neoplasms benign, malignant and unspecified (incl cysts and polyps)System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.1Level: PTClassification code 10028997Term: Neoplasm malignantSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.1Level: HLGTClassification code 10027655Term: Miscellaneous and site unspecified neoplasms malignant and unspecifiedSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2011-005718-12-ES
• Lead Sponsor: ARIAD Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2012-03-28
• Last Update Posted: 19 April 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 137

Inclusion Criteria

All patients must meet all the following eligibility criteria for study entry.
1. All patients must have tumor tissue available for analysis. If sufficient tissue is not available, patients must undergo a biopsy to obtain adequate samples. Patients with less tissue than required can be enrolled only with prior approval from the Sponsor.
In the expansion cohorts, for which failure of prior therapy is specified (expansion cohorts 2 and 3), tumor tissue must be obtained following failure of the prior therapy.
2. Must have measurable disease by RECIST (version 1.1).
3. Male or female patients >= 18 years old.
4. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
5. Minimum life expectancy of 3 months or more.
6. Adequate renal and hepatic function as defined by the following criteria:
i. Total serum bilirubin <= 2 x upper limit of normal (ULN);
ii. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
<= 2.5 x ULN (or <= 5 x ULN if liver function abnormalities are due to underlying malignancy);
iii. Serum creatinine < 2 x ULN;
iv. Serum albumin >= 2 g/dL.
7. Adequate bone marrow function as defined by the following criteria:
i. Absolute neutrophil count (ANC) >= 1500/µL;
ii. Platelets >=75,000/µL;
iii. Hemoglobin >= 9.0 g/dL.
8. Normal QT interval on screening electrocardiogram (ECG) evaluation, defined as QTcF of <= 450 ms in males or <= 470 ms in females.
9. For females of childbearing potential, a negative pregnancy test must be documented prior to enrollment.
10. Female and male patients who are of childbearing potential must agree to use an effective form of contraception with their sexual partners throughout study participation.
11. Signed and dated informed consent indicating that the patient has been informed of all pertinent aspects of the study.
12. Willingness and ability to comply with scheduled visits and study procedures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100

Exclusion Criteria

Patients are not eligible for participation in the study if they meet or have any of the following exclusion criteria:
1. Received an investigational agent within 14 days prior to initiating AP26113.
2. Received systemic anticancer therapy or radiation therapy within 14 days prior to initiating AP26113
a. Except that for cohorts 3 and 4, EGFR TKI therapy is allowed up to 72 hours
prior to initiating AP26113.
3. Major surgery within 28 days prior to initiating AP26113.
4. Active metastases in the brain or central nervous system (CNS). If present, metastases must be stable for at least 8 weeks as documented by magnetic resonance imaging (MRI) or, in the case of meningeal involvement, by a negative lumbar puncture prior to study entry.
5. Significant uncontrolled or active cardiovascular disease, specifically including, but not restricted to:
a. Myocardial infarction, unstable angina and/or congestive heart failure within
3 months prior to first dose of AP26113;
b. History of clinically significant (as determined by the treating physician) atrial
arrhythmia or any ventricular arrhythmia.
6. Uncontrolled hypertension (Diastolic blood pressure [BP] > 100 mm Hg; Systolic
> 150 mm Hg).
7. Prolonged QTcF interval, or being treated with medications known to cause Torsades
de Pointes (refer to Attachment 4).
8. Ongoing or active infection. The requirement for IV antibiotics is considered active infection.
9. Known history of human immunodeficiency virus (HIV). Testing is not required in the absence of history.
10. Pregnant or breastfeeding.
11. Malabsorption syndrome or other gastrointestinal illness that could affect oral
absorption of AP26113.
12. Any condition or illness that, in the opinion of the Investigator, would compromise patient safety or interfere with the evaluation of the safety of the drug.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified