Combining trametinib and hydroxychloroquine for treating advanced pancreatic cancer

PaTcH Trial: A Phase 2 Study to Explore Primary and Emerging Resistance Mechanisms in Patients With Metastatic Refractory Pancreatic Cancer Treated With Trametinib and Hydroxychloroquine

This study is testing if combining two drugs, trametinib and hydroxychloroquine, can help people with advanced pancreatic cancer who haven't responded to other treatments.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 22 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Cancer Trials Ireland (Research network)
• Drugs / interventions: trametinib
• Locations: 2 sites (Dublin and 1 other locations)
• Trial ID: NCT05518110 on ClinicalTrials.gov

What this trial studies

This Phase 2 clinical trial investigates how to overcome treatment resistance in metastatic refractory pancreatic cancer by using a combination of trametinib, an established anticancer drug, and hydroxychloroquine. The study will enroll 10-22 patients who have previously progressed on at least one line of systemic therapy and are not candidates for surgical resection. Participants will be monitored for their response to the treatment and any emerging resistance mechanisms will be explored. The trial aims to provide insights into the effectiveness of this drug combination in a challenging cancer type.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with advanced metastatic pancreatic adenocarcinoma who have previously received systemic therapy.

Not a fit: Patients with early-stage pancreatic cancer or those who have not received prior systemic therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve treatment outcomes for patients with advanced pancreatic cancer who have limited options.

How similar studies have performed: While there have been studies exploring similar drug combinations, this specific approach in metastatic pancreatic cancer is novel.

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.

Where this trial is running

Dublin and 1 other locations

• Mater Misericordiae University Hospital — Dublin, Ireland (Recruiting)
• St Vincent's University Hospital — Dublin, Ireland (Recruiting)

Study contacts

• Principal investigator: Austin Duffy — Mater Misericordiae University Hospital
• Study coordinator: Cancer Trials Ireland

Conditions Pancreatic Cancer; Metastatic refractory; Primary and emerging resistance mechanisms