Adenocarcinoma, Carcinoma, Non-Small-Cell Lung
Conditions
Brief summary
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
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.
Interventions
DRUGVAL401
Risperidone formulated into a liquid lipid filled capsule
Sponsors
ValiSeek Limited
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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informed consent prior to any study-specific screening procedures with the understanding that the consent may be withdrawn by the patient at any time without prejudice.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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | 6 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Reporting Adverse Events and Serious Adverse Events | 6 months | 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. |
| Number of Patients With Disease Control | 6 months | 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. |
| Peak Plasma Concentration (Cmax) | 1 Day and 2 weeks | 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. |
| Patient Quality of Life During VAL401 Treatment | 6 months | Changes in patient quality of life measured by EORTC Health-related Quality of Life (HRQoL) assessment questionnaire QLQ-C30 (Cancer specific questionnaire). |
| Plasma VAL401 Half-life (t 1/2) | 1 Day and 2 weeks | 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. |
| Overall Survival | 6 months | Defined as the time from screening to death if the patient dies within the period that the site is open |
| Trough Plasma Concentration (Cmin) | 1 Day and 2 weeks | 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. |
Participant flow
Recruitment details
Recruitment period: 31 October 2016 - 19 June 2017
Participants by arm
| Arm | Count |
|---|---|
| VAL401 Treatment Patients received VAL401 oral formulation once daily according to their level of tolerance (2 mg - 10 mg) | 8 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Death | 2 |
| Overall Study | Physician Decision | 3 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | VAL401 Treatment |
|---|---|
| Age, Continuous | 65.8 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Region of Enrollment Georgia | 8 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 5 Participants |
| Smokers Ex-smokers | 4 Participants |
| Smokers Never-smokers | 4 Participants |
| Smokers Smokers | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 8 |
| other Total, other adverse events | 8 / 8 |
| serious Total, serious adverse events | 1 / 8 |
Outcome results
Primary
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.
Time frame: 6 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| VAL401 Treatment - Intention to Treat Group | Progression-free Survival (PFS) | 5.2 weeks |
| VAL401 Treatment - Per Protocol Group | Progression-free Survival (PFS) | 7.2 weeks |
Secondary
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.
Time frame: 6 months
Population: Total number of patients reporting Adverse Events or Serious Adverse Events (excluding death)
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| VAL401 Treatment - Intention to Treat Group | Number of Participants Reporting Adverse Events and Serious Adverse Events | Serious Adverse Events Reported | Number participants reporting no events | 7 Participants |
| VAL401 Treatment - Intention to Treat Group | Number of Participants Reporting Adverse Events and Serious Adverse Events | Adverse Events reported | Number participants reporting events | 8 Participants |
| VAL401 Treatment - Intention to Treat Group | Number of Participants Reporting Adverse Events and Serious Adverse Events | Adverse Events reported | Number participants reporting no events | 0 Participants |
| VAL401 Treatment - Intention to Treat Group | Number of Participants Reporting Adverse Events and Serious Adverse Events | Serious Adverse Events Reported | Number participants reporting events | 1 Participants |
Secondary
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.
Time frame: 6 months
Population: Participants scheduled to receive scans at screening, 3 months and 6 months. 2 participants attended CT scans at 3 months, or at their final visit (if earlier).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| VAL401 Treatment - Intention to Treat Group | Number of Patients With Disease Control | Participants receiving mid-treatment CT scan | 2 Participants |
| VAL401 Treatment - Intention to Treat Group | Number of Patients With Disease Control | Primary target tumour increased by 10% or less | 2 Participants |
| VAL401 Treatment - Intention to Treat Group | Number of Patients With Disease Control | Participants demonstrating Complete Response | 0 Participants |
| VAL401 Treatment - Intention to Treat Group | Number of Patients With Disease Control | Participants demonstrating Partial Response | 0 Participants |
| VAL401 Treatment - Intention to Treat Group | Number of Patients With Disease Control | Participants demonstrating Progressive disease | 0 Participants |
| VAL401 Treatment - Intention to Treat Group | Number of Patients With Disease Control | Participants demonstrating Stable Disease | 2 Participants |
Secondary
Overall Survival
Defined as the time from screening to death if the patient dies within the period that the site is open
Time frame: 6 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| VAL401 Treatment - Intention to Treat Group | Overall Survival | 7.8 weeks |
| VAL401 Treatment - Per Protocol Group | Overall Survival | 10.9 weeks |
Secondary
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).
Time frame: 6 months
Population: Each question is scored on a scale of 1 to 4, with each patient assessed for improvement or deterioration of Quality of Life for each life category stated. The number of patients, improving, deteriorating or remaining stable for each measure is reported out of the total of 8 patients assessed.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| VAL401 Treatment - Intention to Treat Group | Patient Quality of Life During VAL401 Treatment | Improvement in nausea/vomiting | Not measured | 2 Participants |
| VAL401 Treatment - Intention to Treat Group | Patient Quality of Life During VAL401 Treatment | Improvement in depression | Status maintained | 2 Participants |
| VAL401 Treatment - Intention to Treat Group | Patient Quality of Life During VAL401 Treatment | Improvement in depression | Status deteriorated | 2 Participants |
| VAL401 Treatment - Intention to Treat Group | Patient Quality of Life During VAL401 Treatment | Improvement in depression | Status improved | 2 Participants |
| VAL401 Treatment - Intention to Treat Group | Patient Quality of Life During VAL401 Treatment | ECOG data | Not measured | 4 Participants |
| VAL401 Treatment - Intention to Treat Group | Patient Quality of Life During VAL401 Treatment | ECOG data | Status maintained | 3 Participants |
| VAL401 Treatment - Intention to Treat Group | Patient Quality of Life During VAL401 Treatment | ECOG data | Status deteriorated | 1 Participants |
| VAL401 Treatment - Intention to Treat Group | Patient Quality of Life During VAL401 Treatment | ECOG data | Status improved | 0 Participants |
| VAL401 Treatment - Intention to Treat Group | Patient Quality of Life During VAL401 Treatment | Improvement in pain | Not measured | 2 Participants |
| VAL401 Treatment - Intention to Treat Group | Patient Quality of Life During VAL401 Treatment | Improvement in pain | Status maintained | 2 Participants |
| VAL401 Treatment - Intention to Treat Group | Patient Quality of Life During VAL401 Treatment | Improvement in pain | Status deteriorated | 0 Participants |
| VAL401 Treatment - Intention to Treat Group | Patient Quality of Life During VAL401 Treatment | Improvement in pain | Status improved | 4 Participants |
| VAL401 Treatment - Intention to Treat Group | Patient Quality of Life During VAL401 Treatment | Improvement in Insomnia | Not measured | 2 Participants |
| VAL401 Treatment - Intention to Treat Group | Patient Quality of Life During VAL401 Treatment | Improvement in Insomnia | Status maintained | 3 Participants |
| VAL401 Treatment - Intention to Treat Group | Patient Quality of Life During VAL401 Treatment | Improvement in Insomnia | Status deteriorated | 1 Participants |
| VAL401 Treatment - Intention to Treat Group | Patient Quality of Life During VAL401 Treatment | Improvement in Insomnia | Status improved | 2 Participants |
| VAL401 Treatment - Intention to Treat Group | Patient Quality of Life During VAL401 Treatment | Improvement in lack of appetite | Not measured | 2 Participants |
| VAL401 Treatment - Intention to Treat Group | Patient Quality of Life During VAL401 Treatment | Improvement in lack of appetite | Status maintained | 3 Participants |
| VAL401 Treatment - Intention to Treat Group | Patient Quality of Life During VAL401 Treatment | Improvement in lack of appetite | Status deteriorated | 1 Participants |
| VAL401 Treatment - Intention to Treat Group | Patient Quality of Life During VAL401 Treatment | Improvement in lack of appetite | Status improved | 2 Participants |
| VAL401 Treatment - Intention to Treat Group | Patient Quality of Life During VAL401 Treatment | Improvement in nausea/vomiting | Status maintained | 4 Participants |
| VAL401 Treatment - Intention to Treat Group | Patient Quality of Life During VAL401 Treatment | Improvement in nausea/vomiting | Status deteriorated | 0 Participants |
| VAL401 Treatment - Intention to Treat Group | Patient Quality of Life During VAL401 Treatment | Improvement in nausea/vomiting | Status improved | 2 Participants |
| VAL401 Treatment - Intention to Treat Group | Patient Quality of Life During VAL401 Treatment | Improvement in fatigue | Not measured | 2 Participants |
| VAL401 Treatment - Intention to Treat Group | Patient Quality of Life During VAL401 Treatment | Improvement in fatigue | Status maintained | 1 Participants |
| VAL401 Treatment - Intention to Treat Group | Patient Quality of Life During VAL401 Treatment | Improvement in fatigue | Status deteriorated | 2 Participants |
| VAL401 Treatment - Intention to Treat Group | Patient Quality of Life During VAL401 Treatment | Improvement in fatigue | Status improved | 3 Participants |
| VAL401 Treatment - Intention to Treat Group | Patient Quality of Life During VAL401 Treatment | Improvement in irritability | Not measured | 2 Participants |
| VAL401 Treatment - Intention to Treat Group | Patient Quality of Life During VAL401 Treatment | Improvement in irritability | Status maintained | 2 Participants |
| VAL401 Treatment - Intention to Treat Group | Patient Quality of Life During VAL401 Treatment | Improvement in irritability | Status deteriorated | 3 Participants |
| VAL401 Treatment - Intention to Treat Group | Patient Quality of Life During VAL401 Treatment | Improvement in irritability | Status improved | 1 Participants |
| VAL401 Treatment - Intention to Treat Group | Patient Quality of Life During VAL401 Treatment | Improvement in depression | Not measured | 2 Participants |
| VAL401 Treatment - Intention to Treat Group | Patient Quality of Life During VAL401 Treatment | Improvement in anxiety | Not measured | 2 Participants |
| VAL401 Treatment - Intention to Treat Group | Patient Quality of Life During VAL401 Treatment | Improvement in anxiety | Status maintained | 1 Participants |
| VAL401 Treatment - Intention to Treat Group | Patient Quality of Life During VAL401 Treatment | Improvement in anxiety | Status deteriorated | 3 Participants |
| VAL401 Treatment - Intention to Treat Group | Patient Quality of Life During VAL401 Treatment | Improvement in anxiety | Status improved | 2 Participants |
| VAL401 Treatment - Intention to Treat Group | Patient Quality of Life During VAL401 Treatment | Improvement in diarrhoea | Not measured | 2 Participants |
| VAL401 Treatment - Intention to Treat Group | Patient Quality of Life During VAL401 Treatment | Improvement in diarrhoea | Status maintained | 4 Participants |
| VAL401 Treatment - Intention to Treat Group | Patient Quality of Life During VAL401 Treatment | Improvement in diarrhoea | Status deteriorated | 1 Participants |
| VAL401 Treatment - Intention to Treat Group | Patient Quality of Life During VAL401 Treatment | Improvement in diarrhoea | Status improved | 1 Participants |
Secondary
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.
Time frame: 1 Day and 2 weeks
Population: Pharmacokinetic measurements include total of Risperidone plus metabolite 9-hydroxy-Risperidone as total actives~Note: 3 out of 8 patients completed PK analysis at Day 15, the remaining 5 patients did not undergo Day 15 PK analysis due to protocol deviations or early withdrawal from the trial.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| VAL401 Treatment - Intention to Treat Group | Peak Plasma Concentration (Cmax) | 30.5 ng/mL |
| VAL401 Treatment - Per Protocol Group | Peak Plasma Concentration (Cmax) | 20 ng/mL |
| VAL401 Treatment - Day 15 (6 mg) | Peak Plasma Concentration (Cmax) | 102 ng/mL |
| VAL401 Treatment - Day 15 (8 mg) | Peak Plasma Concentration (Cmax) | 464 ng/mL |
Secondary
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.
Time frame: 1 Day and 2 weeks
Population: Pharmacokinetic measurements include total of Risperidone plus metabolite 9-hydroxy-Risperidone as total actives.~Note: 3 out of 8 patients completed PK analysis at Day 15, the remaining 5 patients did not undergo Day 15 PK analysis due to protocol deviations or early withdrawal from the trial.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| VAL401 Treatment - Intention to Treat Group | Plasma VAL401 Half-life (t 1/2) | 9 hours |
| VAL401 Treatment - Per Protocol Group | Plasma VAL401 Half-life (t 1/2) | 26 hours |
| VAL401 Treatment - Day 15 (6 mg) | Plasma VAL401 Half-life (t 1/2) | 30 hours |
| VAL401 Treatment - Day 15 (8 mg) | Plasma VAL401 Half-life (t 1/2) | 16 hours |
Secondary
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.
Time frame: 1 Day and 2 weeks
Population: Pharmacokinetic measurements include total of Risperidone plus metabolite 9-hydroxy-Risperidone as total actives.~Note: 3 out of 8 patients completed PK analysis at Day 15, the remaining 5 patients did not undergo Day 15 PK analysis due to protocol deviations or early withdrawal from the trial.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| VAL401 Treatment - Intention to Treat Group | Trough Plasma Concentration (Cmin) | 10.125 ng/mL |
| VAL401 Treatment - Per Protocol Group | Trough Plasma Concentration (Cmin) | 11 ng/mL |
| VAL401 Treatment - Day 15 (6 mg) | Trough Plasma Concentration (Cmin) | 35 ng/mL |
| VAL401 Treatment - Day 15 (8 mg) | Trough Plasma Concentration (Cmin) | 111 ng/mL |