Advanced cancer/ Pancreatic Ductal Adenocarcinoma Cancer Pancreatic Ductal Adenocarcinoma
Conditions
Interventions
All patients are given gemcitabine and the new drug PLX-7486. Gemcitabine is given intravenously (starting dose of 1000mg/m2) once a week on days 1, 8 and 15 of a 28 day treatment cycle. PLX-7486 is t
Sponsors
NHS Greater Glasgow and Clyde
University of Glasgow
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age = 16 years 2. Able to give written informed consent prior to participating in the trial and any trial related procedures being performed 3. Willingness to comply with scheduled visits, treatment plans, laboratory tests and other trial procedures 4. Karnofsky Performance Score = 70 5. Measurable or evaluable disease. Patient enrolled in the expansion phase should have measurable disease by RECIST v1.1 criteria 6. Dose escalation phase: 6.1. Patients with a histologically or cytologically proven advanced solid tumour refractory to conventional treatment, or for which no conventional therapy exists or is declined by the patient, and where treatment with gemcitabine is an appropriate option. 6.2. Any number of prior lines of therapy permitted 7. Dose expansion phase: 7.1. Patients with histologically or cytologically proven locally advanced or metastatic PDAC with the primary tumour in-situ, in whom single-agent gemcitabine is indicated, either as first-line palliative chemotherapy or second-line chemotherapy following FOLFIRINOX treatment. Previous FOLFIRINOX must be completed = 28 days prior to cycle 1 day 7.2. Patients who have an average cancer-related pain score of 3-8 on the Short Form Brief Pain Inventory within 3 weeks of Cycle 1 Day 1 8. Adequate haematological and biochemical indices as below performed within one week (Day -7 to Day 1) before the patient receives study drug (note: patients must not have received recent red blood cell transfusions within 4 weeks, platelet transfusions within 1 week, or growth factors within 1 week of screening tests) 9. Females of childbearing potential must have a negative pregnancy test within 7 days prior to start of dosing, agree to use adequate contraceptive measures (see section 7.1.7) from the time of the negative pregnancy test up to 6 months after the last dose of study drug, and should not be breast feeding. Non-childbearing potential must be evidenced by fulfilling one of the following criteria at screening: 9.1. Post-menopausal defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments. 9.2. Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation 10. Male patients should be willing to use barrier contraception i.e. condoms and female partners of child bearing potential must agree to use adequate contraceptive measures for the duration of the study and up to 6 months after the completion of the study treatment 11. Able to swallow and absorb oral medications 12. Life expectancy of at least 12 weeks
Exclusion criteria
Exclusion criteria: 1. Any systemic anti-cancer therapy (including investigational medicinal products) within 21 days prior to cycle 1 day 1 (6 weeks for nitrosureas and Mitomycin-C); within 5 half-lives for biological therapy and within 14 days for palliative radiotherapy. 1.1. Dose expansion phase: Prior gemcitabine-based chemotherapy for advanced disease. Prior neo-/adjuvant gemcitabine completed = 6 months prior to cycle 1 day 1 is permitted. 2. Unresolved significant toxicity from prior therapy (except alopecia and Grade 1 toxicities, which in the opinion of the Investigator should not exclude patients). If uncertain, please contact the CTU to raise with the Chief Investigator. 3. Known leptomeningeal involvement, brain metastases or spinal cord compression, history of seizures or any condition that may predispose to seizure, including alcoholism 4. Known hypersensitivity (> Grade 2) to pyrimidine antimetabolites, PLX-7486 or structurally/ chemically similar drugs 5. Any gastrointestinal condition that may affect drug absorption of PLX-7486: malabsorption syndrome, previous gastrointestinal surgery (previous Whipples resection permitted), bowel obstruction, current refractory nausea or vomiting 6. Patients with uncontrolled diabetes 7. Treatment with warfarin. Patients on warfarin for DVT-PE can be converted to LMWH or oral Factor Xa inhibitors e.g. Rivaroxaban 8. Any severe or uncontrolled systemic disease (including active infection) or evidence of any other significant disorder or lab finding that the Investigator considers would make it undesirable for the patient to participate in the trial e.g. interstitial lung disease, severe hepatic impairment, uncontrolled chronic renal disease. 9. Known to be serologically positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV). 10. Resting ECG with measurable QTcF = 450 msec (for males) or =470 msec (for females) at screening. Known Left ventricular (LV) dysfunction outside the institutional range of normal (testing not required) 11. Current malignancies other types, with the exception of adequately treated cone-biopsied in-situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin. Cancer survivors, who have undergone potentially curative therapy for a prior malignancy who have no evidence of that disease for the last 3 years are eligible for the study. 12. Patients participating in or planning to participate in another interventional clinical trial whilst on this study. Participation in an observational trial is acceptable. 13.In the Investigator’s opinion, any other condition which would not make the patient a good candidate for the clinical trial
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| 1. Pharmacokinetic (PK) profile of PLX-7486 is measured by taking blood samples from patients enrolled in the escalation phase of the study at defined timepoints on Cycle 1 day 15. These will be analysed by PPD Bioanalytical laboratories to determine the PK profile of PLX-7486. 2. Preliminary anti-tumour activity of PLX-7486 in combination with gemcitabine is measured using RECIST 1.1 every 8 weeks during treatment. | — |
Primary
| Measure | Time frame |
|---|---|
| 1. Safety and tolerability profile is measured by reviewing adverse events (using NCI CTCAE v4.03)at weekly intervals. Sites will be asked to submit weekly DLT forms and these will be discussed at regular Safety Review Committee meetings. 2. Recommended Phase II dose of PLX-7486 in combination with gemcitabine is measured using a standard 3+3 design as described above. The Recommended Phase II dose of PLX-7486 with gemcitabine will be that which results in no more than 1 DLT in 6 patients. | — |
Countries
United Kingdom
Contacts
Public ContactCarol Evans
Outcome results
None listed