PaTcH Study: A Phase 2 Study of Trametinib and Hydroxychloroquine in Patients With Metastatic Refractory Pancreatic Cancer

Trial Title: PaTcH Study: A Phase 2 Study of Trametinib and Hydroxychloroquine in Patients With Metastatic Refractory Pancreatic Cancer

NCT ID: NCT05518110

Condition: Pancreatic Cancer

Conditions: Official terms:
Pancreatic Neoplasms
Hydroxychloroquine
Trametinib

Conditions: Keywords:
Metastatic refractory
Primary and emerging resistance mechanisms

Study type: Interventional

Study phase: Phase 2

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Trametinib
Description: 2mg of Trametinib (orally) daily.
Arm group label: PaTcH

Intervention type: Drug
Intervention name: Hydroxychloroquine
Description: 1200mg of Hydroxychloroquine (orally; 600mg twice a day (BID)) daily.
Arm group label: PaTcH

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.

Criteria for eligibility:
Criteria:
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 exclusion criteria apply: 1. Persisting toxicity related to prior therapy (CTCAE Grade > 1); however alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤2 AEs not constituting a safety risk based on investigator's judgment are acceptable. 2. Prior treatment with a MEK inhibitor 3. Known history of testing positive for Human Immunodeficiency Virus (HIV) or known acquired immunodeficiency syndrome. 4. Any significant disease that, in the opinion of the investigator, may impair the patient's tolerance of study treatment. 5. Patients who are receiving any other investigational agents within 28 days before start of study treatment. 6. Prior organ transplantation including allogenic stem-cell transplantation. 7. Patients with known central nervous system metastases. 8. Active uncontrolled infection, requiring systemic therapy. 9. Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication. 10. Severe left ventricular dysfunction as defined by ejection fraction < 45% 11. Other severe acute or chronic medical conditions including colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behaviour; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study. 12. Known maculopathy of the eye 13. Known history or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes) 14. Screening corrected QT interval by Fridericia (QTcF) > 500 msec 15. Pregnant women and breastfeeding mothers are excluded due to unknown impact on embryos or infants 16. Known prior severe hypersensitivity to investigational products or any component in its formulation. 17. Concurrent use of medicines known to induce retinal toxicity (e.g. tamoxifen) or QT interval prolonging agents. 18. Known congenital or documented acquired QT prolongation. 19. Uncorrected hypokalemia and/or hypomagnesemia.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Mater Misericordiae University Hospital

Address:
City: Dublin
Zip: D07 R2WY
Country: Ireland

Status: Recruiting

Contact:
Last name: Austin Duffy

Investigator:
Last name: Austin Duffy
Email: Principal Investigator

Facility:
Name: St Vincent's University Hospital

Address:
City: Dublin
Zip: DO4 T6F4
Country: Ireland

Status: Recruiting

Contact:
Last name: Ray McDermott

Investigator:
Last name: Ray McDermott
Email: Principal Investigator

Start date: May 31, 2023

Completion date: June 30, 2026

Lead sponsor:
Agency: Cancer Trials Ireland
Agency class: Other

Collaborator:
Agency: Novartis
Agency class: Industry

Source: Cancer Trials Ireland

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05518110