A Study of VAL401 in the Treatment of Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer

Study Overview
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Brief Summary
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The objectives of this study are to assess the safety, tolerability, pharmacokinetics and efficacy of VAL401 in the treatment of patients with locally advanced or metastatic non-small cell lung adenocarcinoma.

Detailed Description
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This is a Phase II, open label study to assess the efficacy, safety and tolerability of VAL401 in the treatment of patients with locally advanced or metastatic non-small cell lung adenocarcinoma after failure of at least one prior chemotherapeutic regimen. Eligible patients will be enrolled as a single cohort and treated with VAL401, given as oral capsules. VAL401 is a formulation of Risperidone (active pharmaceutical ingredient) in a liquid lipid filled capsule.

Official Title
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A Phase II Study to Assess the Efficacy, Safety and Tolerability of VAL401 in the Treatment of Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) After Failure of at Least One Prior Chemotherapeutic Regimen

Conditions
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Carcinoma, Non-Small-Cell Lung, Adenocarcinoma

Intervention / Treatment
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* Drug: VAL401


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically confirmed diagnosis of Stage IIIB or Stage IV adenocarcinoma of the lung. Patients with mixed histology will be eligible if adenocarcinoma is the predominant histology. Measurable disease according to RECIST version 1.1. Prior chemotherapy for relapsed or metastatic non small cell lung cancer. Life expectancy of at least 3 months. Negative human chorionic gonadotropin (hCG) test in women of childbearing potential (defined as women ≤ 50 years of age or history of amenorrhea for ≤ 12 months prior to study screening). Sexually active male and female patients of childbearing potential must agree to use an effective method of birth control e.g. barrier methods with spermicides, oral or parenteral contraceptives and/or intrauterine devices, during the entire duration of the study and for 1 month after the final administration of VAL401. Note that female patients may be surgically sterile (with appropriate documentation in the patient's medical records). Ability to give written, informed consent prior to any study-specific screening procedures with the understanding that the consent may be withdrawn by the patient at any time without prejudice. Patient is capable of understanding the protocol requirements, is willing and able to comply with the study protocol procedures, and has signed the informed consent document. Exclusion Criteria: Radiotherapy or surgery (other than biopsy) within 4 weeks prior to Cycle 1 Day 1. Any chemotherapy regimens (including investigational agents) with delayed toxicity with 6 weeks of Cycle 1 Day 1, or received any chemotherapy regimens given continuously or on a weekly basis which have limited potential for delayed toxicity within 2 weeks prior to Cycle 1 Day 1. Palliative treatment regimens, and other concomitant drugs regimens are permitted with stable toxicity, and recording of all concomitant medications (including herbal). Pregnant or lactating female patients. Active hepatitis B or C or other active liver disease (other than malignancy). Any active, clinically significant, viral, bacterial, or systemic fungal infection within 2 weeks prior to Cycle 1 Day 1; other than cytomegalovirus which may be present providing any required concomitant anti-viral treatment is recorded appropriately. Known human immunodeficiency virus positivity. History of clinically significant cardiac condition, including ischemic cardiac event, myocardial infarction or unstable cardiac disease with 3 months prior to Cycle 1 Day 1. Active brain metastases (defined as stable for <4 weeks and/or symptomatic and/or requiring treatment with anticonvulsants or steroids and/or leptomeningeal disease). Any known contraindications to Risperidone or patients who would not be eligible to receive the treatment as defined in the Special Warnings and Precautions section of the local label for Risperidone. Any medical history that in the Investigator's opinion would jeopardise compliance with the protocol.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VAL401 treatment<br>Patients received VAL401 oral formulation once daily according to their level of tolerance (2 mg - 10 mg). | Drug: VAL401<br>* Risperidone formulated into a liquid lipid filled capsule<br>* Other names: Risperidone lipid formulation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) | PFS is defined as the time from screening to disease progression (or death if the patient died before progression), with progression date nominally defined as the date the patient was withdrawn from the trial, where the Principal Investigator has determined by their professional discretion the patient has symptomatic disease progression. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Quality of Life During VAL401 Treatment | Changes in patient quality of life measured by EORTC Health-related Quality of Life (HRQoL) assessment questionnaire QLQ-C30 (Cancer specific questionnaire). | 6 months | 
| Number of Participants Reporting Adverse Events and Serious Adverse Events | Ongoing evaluation of Adverse Events during treatment with VAL401. Events assessed for number of patients affected, severity of event, likelihood of event being related to the drug treatment and whether the event is an expected/known side effect of Risperidone. | 6 months | 
| Number of Patients With Disease Control | Objective tumour response rates according to RECIST 1.1 for target lesions and assessed by CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. | 6 months | 
| Peak Plasma Concentration (Cmax) | Assessment of Cmax in collected blood samples on Day 1 and Day 15 of Cycle 1, collected at time points: pre-dose (0h) then 10, 15, 30 minutes, 1, 2, 4, 8, 10 and 24 hours after administration of VAL401. | 1 Day and 2 weeks | 
| Trough Plasma Concentration (Cmin) | Assessment of trough plasma concentration (Cmin) in collected blood samples on Day 1 and Day 15 of Cycle 1, collected at time points: pre-dose (0h) then 10, 15, 30 minutes, 1, 2, 4, 8, 10 and 24 hours after administration of VAL401. | 1 Day and 2 weeks | 
| Plasma VAL401 Half-life (t 1/2) | Assessment of plasma half-life of VAL401 (t 1/2) in collected blood samples on Day 1 and Day 15 of Cycle 1, collected at time points: pre-dose (0h) then 10, 15, 30 minutes, 1, 2, 4, 8, 10 and 24 hours after administration of VAL401. | 1 Day and 2 weeks | 
| Overall Survival | Defined as the time from screening to death if the patient dies within the period that the site is open | 6 months |