A clinical trial comparing X-396 (study drug) to Crizotinib in lung cancer patients.

Phase 1

• Conditions: on small cell lung cancer; MedDRA version: 19.0Level: PTClassification code 10029522Term: Non-small cell lung cancer stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 19.0Level: PTClassification code 10029521Term: Non-small cell lung cancer stage IIIBSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 19.0Level: PTClassification code 10059515Term: Non-small cell lung cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 19.0Level: PTClassification code 10029515Term: Non-small cell lung cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2015-004147-40-ES
• Lead Sponsor: Xcovery Holding Company, LLC

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-06-09
• Last Update Posted: 8 August 2016

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 402

Inclusion Criteria

1. Histologically or cytologically confirmed diagnosis of advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC that is ALK-positive as assessed by the Ventana IHC assay. Patients may have received up to 1 prior chemotherapy regimen, which may also include maintenance therapy.
2. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 to 2.
3. Life expectancy of at least 12 weeks.
4. Ability to swallow and retain oral medication.
5. Adequate organ system function, defined as follows:
a. Absolute neutrophil count (ANC) > or = 1.5 x 109/L
b. Platelets > or =100 x 109/L
c. Hemoglobin > or =9 g/dL (> or =90 g/L)
d. Total bilirubin < or =1.5 times the upper limit of normal (ULN)
e. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < or =2.5 x ULN if no liver involvement or < or =5 x ULN with liver involvement.
f. Creatinine < or =1.5 x ULN. If >1.5 x ULN, patient may still be eligible if calculated creatinine clearance > or =50 mL/min (0.83 mL/s) as calculated by the Cockcroft-Gault method.
6. Brain metastases allowed if asymptomatic at study baseline. Patients with untreated brain metastases must not be on corticosteroids. If patients have
neurological symptoms or signs due to CNS metastases, patients need to complete whole brain radiation or focal treatment at least 14 days before start of study treatment and be asymptomatic on stable or decreasing doses of corticosteroids at baseline.
7. Men willing to use adequate contraceptive measures.
8. Women who are not of child-bearing potential, and women of child-bearing potential who agree to use adequate contraceptive measures and who have
a negative serum or urine pregnancy test within 1 week prior to initial trial treatment.
9. Patients must be > or = 18 years of age.
10. Patients must have measurable disease per RECIST v. 1.1.
11. Patients must be ALK-positive by IHC. Testing will be done centrally;
however, patients will be allowed to enroll based on local results (positive by FISH or IHC), if available.
12. Willingness and ability to comply with the trial and follow-up procedures.
13. Ability to understand the nature of this trial and give written informed consent.
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 302
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100

Exclusion Criteria

1. Patients that have previously received an ALK TKI, and patients currently receiving cancer therapy (i.e., other targeted therapies, chemotherapy, radiation therapy, immunotherapy, biologic therapy, hormonal therapy, surgery and/or tumor embolization).
2. Use of an investigational drug within 21 days prior to the first dose of study drug. Note that to be eligible, any drug-related toxicity should have recovered to Grade 1 or less, with the exception of alopecia.
3. Any chemotherapy within 4 weeks, or major surgery or radiotherapy within the last 14 days.
4. Patients with primary CNS tumors and leptomeningeal disease are ineligible.
5. Patients with a previous malignancy within the past 3 years (other than curatively treated basal cell carcinoma of the skin, in situ carcinoma of the cervix, or any cancer that is considered to be cured and have no impact on PFS and OS for the current NSCLC).
6. Concomitant use of drugs with a risk of causing Torsades de Pointes within 14 days prior to starting study drug.
7. Concomitant use of herbal medications. These should be stopped prior to study entry.
8. Patients receiving strong CYP3A inhibitors or inducers.
9. Women who are pregnant or breastfeeding.
10. Presence of active gastrointestinal (GI) disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of study medications.
11. Clinically significant cardiovascular disease including:
a. QTcF interval > o = 450 ms, symptomatic bradycardia <45 beats per minute or other significant ECG abnormalities in the investigator’s opinion.
b. Clinically uncontrolled hypertension in the investigator’s opinion (e.g., blood pressure >160/100 mmHg; note that isolated elevated readings considered to not be indicative of uncontrolled hypertension are allowed).
The following within 6 months prior to Cycle 1 Day 1:
a. Congestive heart failure (New York Heart Class III or IV).
b. Arrhythmia or conduction abnormality requiring medication. Note: patients with atrial fibrillation/flutter controlled by medication and arrhythmias controlled by pacemakers are eligible.
c. Severe/unstable angina, coronary artery/peripheral bypass graft, or myocardial infarction.
d. Cerebrovascular accident or transient ischemia.
12. Patients who are immunosuppressed (including known HIV infection), have a serious active infection at the time of treatment, have interstitial lung disease/pneumonitis, or have any serious underlying medical condition that would impair the ability of the patient to receive protocol treatment. Patients with controlled hepatitis C, in the investigator’s opinion, are allowed. Patients with known hepatitis B must be HBeAg and HB viral DNA negative for enrollment. Note that, because of the high prevalence, all patients in the Asia-Pacific region (except Australia, New Zealand, and Japan) must be tested and, if HBsAg positive, must be HBeAg and HB viral DNA negative for enrollment.
13. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
14. Concurrent condition that in the investigator’s opinion would jeopardize compliance with the protocol or would impart excessive risk associated with study participation that would make it inappropriate for the patient to be enrolled.
15. Inability or unwillingness to comply with study and/or follow-up procedures outlined in the protocol.

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy and safety of X-396 vs. crizotinib in patients with ALK-positive NSCLC that have received up to 1 prior chemotherapy regimen<br>and no prior ALK tyrosine kinase inhibitor (TKI).;Secondary Objective: To obtain additional pharmacokinetic (PK) data on X-396 from sparse PK sampling from patients at selected sites.;Primary end point(s): Progression-free survival (PFS) as assessed by independent radiology review based on RECIST v. 1.1 criteria.;Timepoint(s) of evaluation of this end point: The final analysis (primary analysis) will be performed after 305 PFS events have been observed.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Overall survival, objective response rate (based on independent radiology review), PFS based on investigator assessment, ORR (based on investigator assessment), time to response (based on investigator assessment and independent radiology review), duration of response (based on investigator assessment and independent radiology review), CNS response rate (based on investigator assessment and independent radiology review), time to CNS progression.;Timepoint(s) of evaluation of this end point: The final analysis (secondary efficacy endpoint analysis) will be performed after 305 PFS events have been observed.