Pancreatic Cancer
Conditions
Keywords
Metastatic refractory, Primary and emerging resistance mechanisms
Brief summary
This study is designed to investigate the means by which cancer resists treatment can be overcome by a combination of an established anticancer drug, trametinib, with hydroxychloroquine.
Detailed description
The study is a multi-centre single arm Phase 2 clinical trial to explore primary and emerging resistance mechanisms in patients with metastatic refractory pancreatic cancer treated with trametinib and hydroxychloroquine. This study will include 10-22 patients with metastatic pancreatic cancer who have previously progressed on at least one line of systemic therapy.
Interventions
DRUGTrametinib
2mg of Trametinib (orally) daily.
DRUGHydroxychloroquine
1200mg of Hydroxychloroquine (orally; 600mg twice a day (BID)) daily.
Sponsors
Cancer Trials Ireland
Novartis
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
Each patient must meet all of the following inclusion criteria to be eligible for the study: 1. Patients must have pathologically confirmed advanced metastatic pancreatic adenocarcinoma or poorly differentiated pancreatic adenocarcinoma that is amenable to tumour biopsy. 2. Patients have received at least one line of systemic therapy for metastatic disease and not be amenable to surgical resection. 3. Patients must have measurable disease by RECIST 1.1 criteria. 4. Age ≥18 years. 5. ECOG performance status ≤ 1 6. Patients must have normal organ and marrow function as defined below: 1. Serum creatinine ≤ 1.5 x ULN. 2. Adequate hepatic function defined by: * total bilirubin level ≤ 1.5 × ULN, * an AST, level ≤ 2.5 × ULN, and an ALT level ≤ 2.5 × ULN (or, for subjects with documented metastatic disease to the liver, AST and ALT levels ≤ 5 × ULN) 3. Hematological eligibility parameters: * Absolute Neutrophil count ≥ 1.5 x 109/L * Platelet count ≥100 x109/L * Hemoglobin ≥ 9 g/dL 7. Ability of subject to understand and the willingness to sign a written informed consent document. 8. Women of child-bearing potential or sexually active males must agree to use highly effective contraceptive measures. This applies from starting treatment until at least 16 weeks after the last study drug administration. The investigator or a designated associate is required to advise the patient how to achieve an adequate birth control. Highly effective contraception is defined in the study as methods that achieve a failure rate of less than 1% per year when used consistently and correctly. Such methods include: I. Combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal). II. Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable and implantable). III. Intrauterine device (IUD). IV. Intrauterine hormone-releasing system (IUS). V. Bilateral tubal occlusion. VI. Successfully vasectomised partner. VII. Sexual abstinence.
Exclusion criteria
Patients are excluded from the study if any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Patients free of disease progression | Twelve weeks from starting treatment. | The percentage of patients free of disease progression at 12 weeks from starting treatment into the study as determined by radiographic disease assessments per RECIST version 1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tumour Response Rate | Twelve weeks following the 15th and 22nd patients. | Confirmed tumour response rate as assessed by RECIST version 1.1. |
| Duration of Response | Through study treatment, an average of 1 year | Confirmed duration of response as assessed by RECIST version 1.1. |
| Overall Survival | Through study completion, an average of five years | Overall Survival |
| Safety and tolerability | Through study treatment, an average of one year | The safety and tolerability of this regimen as measured by incidence of adverse events reported and toxicity evaluation as per the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. |
Countries
Ireland
Contacts
PRINCIPAL_INVESTIGATORAustin Duffy
Mater Misericordiae University Hospital
Outcome results
None listed