Dose Finding Safety Study of VAL201 in Cancer Patients (VAL201-001)

A Phase I/II, Dose Escalation Study To Assess The Safety and Tolerability of VAL201 In Patients With Advanced or Metastatic Prostate Cancer and Other Advanced Solid Tumours

Dose finding safety study of VAL201 in cancer patients.

Study Overview

• Status: Completed
• Conditions: Stage III Prostate Carcinoma; Stage IV Prostate Carcinoma
• Intervention / Treatment: Drug: VAL201

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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Exclusion Criteria for Patients with Prostate Cancer Patients has received an anticancer therapy, including investigational agents, within the precious 6 weeks or 4 weeks.
  • Any patients who have undergone prior orchidectomy.
  • Specific Exclusion Criteria for Patients with Other Advanced Solid Tumours Pregnant or lactating female patients.
  • Documented, symptomatic or uncontrolled brain metastases.
  • History of clinically significant cardiac condition, including ischemic cardiac event, myocardial infarction or unstable cardiac disease within 3 months previous to the indication of home therapy.
  • Known Human Immunodeficiency Virus positivity.
  • Active Hepatitis B or C or other active liver disease (other than malignancy).
  • Any active, clinically significant, viral, bacterial, or systemic fungal infection within previous 4 weeks prior to home therapy.
  • Any medical history that would jeopardize compliance.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: 0.5 mg/kg; VAL201-001 Sub-cutaneous injection. 0.5 mg/kg	Drug: VAL201; VAL201-001 Sub-cutaneous injection.; Other Names: VAL201-001
Experimental: Cohort 2: 1 mg/kg; VAL201-001 Sub-cutaneous injection. 1.0 mg/kg	Drug: VAL201; VAL201-001 Sub-cutaneous injection.; Other Names: VAL201-001
Experimental: Cohort 3: 2 mg/kg; VAL201-001 Sub-cutaneous injection. 2.0 mg/kg	Drug: VAL201; VAL201-001 Sub-cutaneous injection.; Other Names: VAL201-001
Experimental: Cohort 4: 4 mg/kg; VAL201-001 Sub-cutaneous injection. 4.0 mg/kg	Drug: VAL201; VAL201-001 Sub-cutaneous injection.; Other Names: VAL201-001
Experimental: 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.	Drug: VAL201; VAL201-001 Sub-cutaneous injection.; Other Names: VAL201-001

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-Limiting Toxicity	The number of Dose-Limiting Toxicity events is used to determine whether a maximum tolerated dose (MTD) is obtained.	The average timeframe is 18-26 weeks per subject

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	The average timeframe is 18-26 weeks per subject
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.	The average timeframe is 18-26 weeks per subject

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	The average timeframe is 18-26 weeks per subject
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.	The average timeframe is 18-26 weeks per subject

Collaborators and Investigators

• Sponsor: ValiRx Plc

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): January 27, 2020
• Study Completion (Actual): January 27, 2020

Study Registration Dates

• First Submitted: October 20, 2014
• First Submitted That Met QC Criteria: October 28, 2014
• First Posted (Estimate): October 31, 2014

Study Record Updates

• Last Update Posted (Actual): November 8, 2021
• Last Update Submitted That Met QC Criteria: October 8, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Carcinoma
• Other Study ID Numbers: VAL201-001; 2013-004009-25 (EudraCT Number)