Stage III Prostate Carcinoma, Stage IV Prostate Carcinoma
Conditions
Brief summary
Dose finding safety study of VAL201 in cancer patients.
Detailed description
A Phase I/II, dose escalation study to assess the safety and tolerability of VAL201 in patients with locally advanced or metastatic prostate cancer and other advanced solid tumours.
Interventions
DRUGVAL201
VAL201-001 Sub-cutaneous injection.
Sponsors
ValiRx Plc
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Dose Escalation sequential assignment
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
The study will enrol patients with locally advanced or metastatic prostate cancer. The MTD/MAD may also be evaluated in patients with other advanced tumour types for whom no standard effective therapy is available and a rationale for use of VAL201 exists. The average timeframe is 18-26 weeks per subject and the outcome measured is a composite average for each group. * Inclusion criteria: * Specific Inclusion Criteria for Patients with Prostate Cancer * Patients with incurable, locally advanced or metastatic prostate cancer where a policy of intermittent hormone therapy has been decided. Who have specific clinical parameters. * Specific Inclusion Criteria for Patients with Other Advanced Solid Tumours * Patients with histologically and/or cytologically confirmed advanced solid tumour for whom no standard effective therapy is available and a rationale for use of VAL201 exists. * Patients with incurable, locally advanced or metastatic prostate cancer where a policy of intermittent hormone therapy has been decided. These patients must also have the following: 1. Rising PSA on three samples (once non-castrate levels established); each over 2 weeks apart, with the last two values being greater than 2 ng/mL. Higher than and at least 25% over the nadir. 2. Absent or very mild prostate cancer-related symptoms. 3. No plans for any therapy for prostate cancer in the next two months. * General Inclusion Criteria for all Patients * Adult patients defined by age greater than 18 years at time of consent. * 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informed consent prior to any study-specific Screening procedures, with the understanding that the consent may be withdrawn by the patient at any time without prejudice.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. * Evaluable disease, either measurable on imaging, or with informative tumour marker(s) and a set of specific biochemical and haematological parameters relating to the specific cancer. * Negative human chorionic gonadotropin (hCG) test in women of childbearing potential. * Sexually active male and female patients of childbearing potential must agree to use an effective method of birth control. Female patients may be surgically sterile. * Laboratory values at Screening: * Absolute neutrophil count ≥1.5 x 109/L. * Platelets ≥100 x 109/L. * Haemoglobin ≥9 g/dL without blood transfusion or colony stimulating factor support. * Total bilirubin \<1.5 times the upper limit of normal (ULN); * AST (SGOT) ≤2.5 times the ULN; * ALT (SGPT) ≤2.5 times the ULN; ≤5 x ULN for patients with advanced solid tumours with liver metastases. * Serum creatinine ≤1.5 x ULN or estimated glomerular filtration rate (GFR) of \>50 mL/min based on the Cockcroft-Gault formula. *
Exclusion criteria
* Specific
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-Limiting Toxicity | The average timeframe is 18-26 weeks per subject | The number of Dose-Limiting Toxicity events is used to determine whether a maximum tolerated dose (MTD) is obtained. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics of VAL201. (Cmax) | The average timeframe is 18-26 weeks per subject | Assessment of pharmacokinetic variables at multiple time points (5 min, 10 min, 15 min, 30 min, 60 min, 90 min, 2 hours, 3 hours, 4 hours, 6 hours and 8 hours after dosing) and multiple dosing days (Cycle 1 Day 1, Cycle 3 Day 1, Cycle 4 Day 1 and Cycle 6 Day 1) for each patient analysed. |
| Pharmacokinetics of VAL201 (AUC 0-inf) | The average timeframe is 18-26 weeks per subject | Assessment of pharmacokinetic variables at multiple time points (5 min, 10 min, 15 min, 30 min, 60 min, 90 min, 2 hours, 3 hours, 4 hours, 6 hours and 8 hours after dosing) and multiple dosing days (Cycle 1 Day 1, Cycle 3 Day 1, Cycle 4 Day 1 and Cycle 6 Day 1) for each patient analysed. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Who Completed 6 Cycles of Treatment | The average timeframe is 18-26 weeks per subject | The number of patients who completed 6 cycles of treatment is compared with the number who withdrew prior to completion of the scheduled 6 cycles |
| Number of Patients Displaying Disease Progression by PCWG2 and/or RECIST Criteria | The average timeframe is 18-26 weeks per subject | Assessment of disease response to treatment by PCWG2 and/or RECIST. Disease progression is defined by RECIST 1.1 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; and by PCWG2 criteria that PSA values did not see an increase of 25% or more and absolute increase of 2 ng/mL or more from the nadir. |
Participant flow
Recruitment details
The study will enrol patients with locally advanced or metastatic prostate cancer. The MTD/MAD may also be evaluated in patients with other advanced tumour types for whom no standard effective therapy is available and a rationale for use of VAL201 exists.
Pre-assignment details
Interventional Study Model; Sequential Assignment -Dose Escalation sequential assignment-
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: 0.5 mg/kg VAL201: VAL201-001 Sub-cutaneous injection 0.5 mg/kg. | 1 |
| Cohort 2: 1 mg/kg VAL201: VAL201-001 Sub-cutaneous injection 1.0 mg/kg. | 1 |
| Cohort 3: 2 mg/kg VAL201: VAL201-001 Sub-cutaneous injection 2.0 mg/kg. | 3 |
| Cohort 4: 4 mg/kg VAL201: VAL201-001 Sub-cutaneous injection 4.0 mg/kg. | 5 |
| Cohort 5: up to 8 mg/kg VAL201-001 Sub-cutaneous injection. 8.0 mg/kg; potential to escalate to 16 mg/kg after 3 cycles according to clinician decision Flexibility of dosing enabled under protocol. | 2 |
| Total | 12 |
Baseline characteristics
| Characteristic | Total | Cohort 1: 0.5 mg/kg | Cohort 2: 1 mg/kg | Cohort 3: 2 mg/kg | Cohort 4: 4 mg/kg | Cohort 5: up to 8 mg/kg |
|---|---|---|---|---|---|---|
| Age, Continuous | 72.4 years | 70 years | 62 years | 76 years | 72.6 years | 73 years |
| Race/Ethnicity, Customized Race/Ethnicity Asian | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Black/African American | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race/Ethnicity White | 10 Participants | 1 Participants | 1 Participants | 2 Participants | 4 Participants | 2 Participants |
| Region of Enrollment United Kingdom | 12 participants | 1 participants | 1 participants | 3 participants | 5 participants | 2 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 12 Participants | 1 Participants | 1 Participants | 3 Participants | 5 Participants | 2 Participants |
| Stage of Cancer at Screening Locally Advanced Prostate Cancer | 7 Participants | 0 Participants | 1 Participants | 2 Participants | 3 Participants | 1 Participants |
| Stage of Cancer at Screening Metastatic Prostate Cancer | 5 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 1 | 0 / 3 | 0 / 5 | 0 / 1 | 0 / 1 |
| other Total, other adverse events | 1 / 1 | 1 / 1 | 3 / 3 | 5 / 5 | 1 / 1 | 1 / 1 |
| serious Total, serious adverse events | 0 / 1 | 0 / 1 | 0 / 3 | 2 / 5 | 1 / 1 | 0 / 1 |
Outcome results
Primary
Dose-Limiting Toxicity
The number of Dose-Limiting Toxicity events is used to determine whether a maximum tolerated dose (MTD) is obtained.
Time frame: The average timeframe is 18-26 weeks per subject
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: 0.5 mg/kg | Dose-Limiting Toxicity | Dose-limiting Toxicity observed (DLT) | 0 Participants |
| Cohort 1: 0.5 mg/kg | Dose-Limiting Toxicity | MTD or MAD proposed | 0 Participants |
| Cohort 1: 0.5 mg/kg | Dose-Limiting Toxicity | Dose-reduction required | 0 Participants |
| Cohort 2: 1.0 mg/kg | Dose-Limiting Toxicity | Dose-reduction required | 0 Participants |
| Cohort 2: 1.0 mg/kg | Dose-Limiting Toxicity | Dose-limiting Toxicity observed (DLT) | 0 Participants |
| Cohort 2: 1.0 mg/kg | Dose-Limiting Toxicity | MTD or MAD proposed | 0 Participants |
| Cohort 3: 2.0 mg/kg | Dose-Limiting Toxicity | Dose-reduction required | 0 Participants |
| Cohort 3: 2.0 mg/kg | Dose-Limiting Toxicity | Dose-limiting Toxicity observed (DLT) | 0 Participants |
| Cohort 3: 2.0 mg/kg | Dose-Limiting Toxicity | MTD or MAD proposed | 0 Participants |
| Cohort 4: 4.0 mg/kg | Dose-Limiting Toxicity | Dose-limiting Toxicity observed (DLT) | 0 Participants |
| Cohort 4: 4.0 mg/kg | Dose-Limiting Toxicity | MTD or MAD proposed | 0 Participants |
| Cohort 4: 4.0 mg/kg | Dose-Limiting Toxicity | Dose-reduction required | 0 Participants |
| Cohort 5: up to 8 mg/kg | Dose-Limiting Toxicity | Dose-reduction required | 0 Participants |
| Cohort 5: up to 8 mg/kg | Dose-Limiting Toxicity | Dose-limiting Toxicity observed (DLT) | 1 Participants |
| Cohort 5: up to 8 mg/kg | Dose-Limiting Toxicity | MTD or MAD proposed | 0 Participants |
Secondary
Pharmacokinetics of VAL201 (AUC 0-inf)
Assessment of pharmacokinetic variables at multiple time points (5 min, 10 min, 15 min, 30 min, 60 min, 90 min, 2 hours, 3 hours, 4 hours, 6 hours and 8 hours after dosing) and multiple dosing days (Cycle 1 Day 1, Cycle 3 Day 1, Cycle 4 Day 1 and Cycle 6 Day 1) for each patient analysed.
Time frame: The average timeframe is 18-26 weeks per subject
Population: Cohort 5 consisted of one participant dosed at 8 mg/kg and one participant dosed at 4 mg/kg, on which pharmacokinetic parameters were measured; pharmacokinetic data was not analysed for Cohorts 1-4. Pharmacokinetic profiles were collected on multiple dosing days.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cohort 1: 0.5 mg/kg | Pharmacokinetics of VAL201 (AUC 0-inf) | 5.0 ug/mL*h |
| Cohort 2: 1.0 mg/kg | Pharmacokinetics of VAL201 (AUC 0-inf) | 3.8 ug/mL*h |
Secondary
Pharmacokinetics of VAL201. (Cmax)
Assessment of pharmacokinetic variables at multiple time points (5 min, 10 min, 15 min, 30 min, 60 min, 90 min, 2 hours, 3 hours, 4 hours, 6 hours and 8 hours after dosing) and multiple dosing days (Cycle 1 Day 1, Cycle 3 Day 1, Cycle 4 Day 1 and Cycle 6 Day 1) for each patient analysed.
Time frame: The average timeframe is 18-26 weeks per subject
Population: Cohort 5 consisted of one participant dosed at 8 mg/kg and one participant dosed at 4 mg/kg, on which pharmacokinetic parameters were measured; pharmacokinetic data was not analysed for Cohorts 1-4. Pharmacokinetic profiles were collected on multiple dosing days.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cohort 1: 0.5 mg/kg | Pharmacokinetics of VAL201. (Cmax) | 3323 ng/mL |
| Cohort 2: 1.0 mg/kg | Pharmacokinetics of VAL201. (Cmax) | 2205 ng/mL |
Other Pre-specified
Number of Patients Displaying Disease Progression by PCWG2 and/or RECIST Criteria
Assessment of disease response to treatment by PCWG2 and/or RECIST. Disease progression is defined by RECIST 1.1 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; and by PCWG2 criteria that PSA values did not see an increase of 25% or more and absolute increase of 2 ng/mL or more from the nadir.
Time frame: The average timeframe is 18-26 weeks per subject
Population: Excludes one participant from Cohort 4 who received a single dose
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: 0.5 mg/kg | Number of Patients Displaying Disease Progression by PCWG2 and/or RECIST Criteria | Showed progressive disease at any point during trial period according to PCWG2 | 0 Participants |
| Cohort 1: 0.5 mg/kg | Number of Patients Displaying Disease Progression by PCWG2 and/or RECIST Criteria | Showed no progressive disease during trial period according to PCWG2 | 1 Participants |
| Cohort 2: 1.0 mg/kg | Number of Patients Displaying Disease Progression by PCWG2 and/or RECIST Criteria | Showed progressive disease at any point during trial period according to PCWG2 | 1 Participants |
| Cohort 2: 1.0 mg/kg | Number of Patients Displaying Disease Progression by PCWG2 and/or RECIST Criteria | Showed no progressive disease during trial period according to PCWG2 | 0 Participants |
| Cohort 3: 2.0 mg/kg | Number of Patients Displaying Disease Progression by PCWG2 and/or RECIST Criteria | Showed no progressive disease during trial period according to PCWG2 | 1 Participants |
| Cohort 3: 2.0 mg/kg | Number of Patients Displaying Disease Progression by PCWG2 and/or RECIST Criteria | Showed progressive disease at any point during trial period according to PCWG2 | 2 Participants |
| Cohort 4: 4.0 mg/kg | Number of Patients Displaying Disease Progression by PCWG2 and/or RECIST Criteria | Showed no progressive disease during trial period according to PCWG2 | 3 Participants |
| Cohort 4: 4.0 mg/kg | Number of Patients Displaying Disease Progression by PCWG2 and/or RECIST Criteria | Showed progressive disease at any point during trial period according to PCWG2 | 1 Participants |
| Cohort 5: up to 8 mg/kg | Number of Patients Displaying Disease Progression by PCWG2 and/or RECIST Criteria | Showed progressive disease at any point during trial period according to PCWG2 | 1 Participants |
| Cohort 5: up to 8 mg/kg | Number of Patients Displaying Disease Progression by PCWG2 and/or RECIST Criteria | Showed no progressive disease during trial period according to PCWG2 | 1 Participants |
Other Pre-specified
Number of Patients Who Completed 6 Cycles of Treatment
The number of patients who completed 6 cycles of treatment is compared with the number who withdrew prior to completion of the scheduled 6 cycles
Time frame: The average timeframe is 18-26 weeks per subject
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: 0.5 mg/kg | Number of Patients Who Completed 6 Cycles of Treatment | Completed 6 cycles of treatment | 1 Participants |
| Cohort 1: 0.5 mg/kg | Number of Patients Who Completed 6 Cycles of Treatment | Withdrew from trial prior to completion | 0 Participants |
| Cohort 2: 1.0 mg/kg | Number of Patients Who Completed 6 Cycles of Treatment | Completed 6 cycles of treatment | 1 Participants |
| Cohort 2: 1.0 mg/kg | Number of Patients Who Completed 6 Cycles of Treatment | Withdrew from trial prior to completion | 0 Participants |
| Cohort 3: 2.0 mg/kg | Number of Patients Who Completed 6 Cycles of Treatment | Completed 6 cycles of treatment | 0 Participants |
| Cohort 3: 2.0 mg/kg | Number of Patients Who Completed 6 Cycles of Treatment | Withdrew from trial prior to completion | 3 Participants |
| Cohort 4: 4.0 mg/kg | Number of Patients Who Completed 6 Cycles of Treatment | Withdrew from trial prior to completion | 4 Participants |
| Cohort 4: 4.0 mg/kg | Number of Patients Who Completed 6 Cycles of Treatment | Completed 6 cycles of treatment | 1 Participants |
| Cohort 5: up to 8 mg/kg | Number of Patients Who Completed 6 Cycles of Treatment | Completed 6 cycles of treatment | 1 Participants |
| Cohort 5: up to 8 mg/kg | Number of Patients Who Completed 6 Cycles of Treatment | Withdrew from trial prior to completion | 1 Participants |