Advanced pancreatic ductal adenocarcinoma Cancer
Conditions
Interventions
CRISTAL-APC is split into two (2) phases and the participants will receive the following treatments:
Phase I: Dose Escalation Phase
CRISTAL-APC will evaluate VP-002 at a total daily dose of 600mg to
Sponsors
Cambridge Clinical Trials Unit (CCTU)
Eligibility
Sex/Gender
All
Age
18 Years to 100 Years
Inclusion criteria
Inclusion criteria: 1. Histologically or cytologically (based on local assessment and per local guidelines) confirmed PDAC and variants. Either of the following: 1.1. Adenosquamous carcinoma 1.2. Ductal adenocarcinoma 1.3. Intraductal papillary mucinous neoplasm (IPMN) with an associated invasive carcinoma 1.4. Mucinous adenocarcinoma 1.5. Mucinous cystic neoplasm (MCN) with an associated invasive carcinoma 1.6. Undifferentiated carcinoma 2. Aged 18 years and over 3. Radiologically confirmed stage IV disease 4. Measurable disease by RECIST version 1.1 4.1. If the patient has received prior radiotherapy to the lesion, it should have progressed since irradiation to be included as a measurable lesion: 5. ECOG PS 0 or 1 6. Estimated life expectancy =12 weeks at screening 7. Adequate bone marrow function: 7.1. Absolute neutrophil count (ANC) =1.5 x 10^9 /L 7.2. Haemoglobin (Hb) =90 g/L for Phase I; =100 g/L for Phase II, with no blood transfusions in the preceding 14 days 7.3. Platelets =100 x 10^9 /L 8. Adequate liver function: 8.1. Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) =2.5 x upper limit of normal range (ULN) (100 cells are present in the sample, or a baseline tumour biopsy 3. Gemcitabine and Nab-paclitaxel deemed reasonable treatment or re-treatment options: 3.1. Have not received it previously OR 3.2. Have received it previously and tolerated treatment without significant dose. Inclusion Criteria – Phase II Specific: 1. Received no prior systemic therapy for stage IV disease; or received prior systemic anti-cancer therapy as neo-adjuvant or adjuvant therapy AND such treatment was completed at least 6 months previously 2. Confirmation of ade
Exclusion criteria
Exclusion criteria: Phase I and Phase II: 1. Patients with operable or locally advanced PDAC 2. Other invasive malignancies with the exception of adequately treated carcinoma in situ of the cervix or non-melanoma skin cancer. Cancer survivors who have undergone potentially curative treatment for a prior malignancy, have no recurrence within the last 2 years and are deemed at negligible risk for recurrence are eligible for trial 3. Significant acute or chronic medical or psychiatric condition, disease or laboratory abnormality which in the judgment of the investigator would place the patient at undue risk or interfere with the trial. Examples include, but are not limited to: 3.1. Patients who have had a venous thromboembolic event who are not appropriately anticoagulated or have had a significant bleeding episode in the 3 weeks prior to randomization 3.2. Patients with symptoms of severe chronic obstructive airways disease or significant shortness of breath at rest AND have an Forced expiratory volume (FEV)1 480 ms msec (confirmation of any prolongation to be used based on the average QT interval by Fridericia (QTcF) value of 3 reads within a 30-minute time period). Concomitant use of medications known to prolong QT interval, or with factors that increase the risk of QTc prolongation or risk of arrhythmic events (such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome), or unexplained sudden death under 40 years of age. Inability to discontinue medication with agents designated as having a risk of Torsades de Pointes due to QT prolongation 6. Concurrent participation in an interventional clinical trial (observational studies allowed) 7. Patients that have not been enrolled onto the Precision Panc Master Protocol Exclusion Criteria – Phase I Specific: 1. Any unresolved toxic effects Grade =2 according to NCI CTCAE v 5.0 from prior chemotherapy administered for locally advanced or metastatic disease (with the exception of alopecia, Gr 2 peripheral neuropathy and haemoglobin =90g/L with no blood transfusions in the preceding 28 days Exclusion Criteria – Phase II Specific: 1. Prior chemotherapy for locally advanced or metastatic pancreatic adenocarcinoma 2. Any unresolved toxic effects Grade =2 according to NCI CTCAE v 5.0 from previous treatment for cancer (adjuvant or neoadjuvant) before randomization, except for alopecia
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase I: 1. MTD (Maximum Tolerated Dose) based on the occurrence of DLTs (Dose Limiting Toxicities) in cycle 0 and cycle 1 (around six weeks from the start of treatment) 2. Incidence of Treatment-Emergent Adverse Events (TEAEs), identified by symptoms, physical examination, ECGs and through clinical laboratory blood and urine sample evaluations (according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0) throughout all cycles of the study 3. Incidence of TEAEs leading to study drug modifications (e.g., interruptions) and discontinuation of the study drug throughout all cycles of the study Phase II: Median overall survival (OS), calculated from the date of randomisation to the date of death for all evaluable patients in each treatment arm across the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Phase I: Safety and tolerability: 1. The frequency of AEs (Grades 3, 4 and 5), and the number of SAEs and DLTs considered at least possibly related to VP-002 occurring in cycle 0 and cycle 1 (around six weeks from the start of treatment), according to NCI CTCAE version 5.0. Anti-tumour activity: 1. ORR (Objective Response Rate), defined as the rate of CR (Complete Response) plus PR (Partial Response) according to Response Evaluation Criteria in Solid Tumours Version 1.1, (RECIST V1.1) This will be measured by CT imaging every 8 weeks from screening, until the end of the study. 2. Best overall response (BOR), the best radiological response from the start of study treatment according to RECIST v1.1 until the end of the study. 3. Changes in CA19.9 from baseline measured in the blood each cycle of treatment until disease progression Pharmacokinetics: 1. Pharmacokinetics of VP-002 including, but not limited to maximum (or peak) plasma concentration (Cmax), time to reach Cmax (Tmax), minimal plasma concentration (Cmin), area under the plasma concentration-time curve (AUC), apparent clearance (CL/F), apparent volume of distribution (V/F) from blood samples taken in cycle 0, cycle 1 and cycle 2. Phase II: Safety and tolerability: 1. Frequency of AEs and SAEs considered at least possibly related to VP-002 and the number of Grade 3, 4 and 5 AEs considered at least possibly related to VP-002 according to NCI CTCAE version 5.0, assessed throughout all cycles until the end of the study. Efficacy: 1. Progression-free survival (PFS): time from the date of randomising VP-002 plus nPG to the date of disease progression or date of death, whichever occurs first. This will be measured by imaging according to RECIST V1.1 every 8 weeks from randomisation until progression or end of study. Surviving patients without progression will be censored at the date of their last clinical follow-up at the time of analysis. 2. Overall survival (OS) at 12 months from randomisation. 3. Disease con | — |
Countries
England, United Kingdom
Contacts
Public ContactElla James
Outcome results
None listed