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

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 designed to investigate the means by which cancer resists treatment can be overcome by a combination of an established anticancer drug, trametinib, with hydroxychloroquine.

Study Overview

• Status: Terminated
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: Trametinib; Drug: 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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• Ireland
  • Dublin, Ireland, D07 R2WY
    • Mater Misericordiae University Hospital
  • Dublin, Ireland, DO4 T6F4
    • St Vincent's University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PaTcH; All eligible patients will be treated with trametinib 2mg and hydroxychloroquine 1200mg daily (600mg twice a day (BID)) orally. Treatment will be continuous in treatment cycles lasting 28 days, and will continue until radiological or clinical progression of disease, unacceptable toxicity or consent withdrawal.	Drug: Trametinib; 2mg of Trametinib (orally) daily.; Drug: Hydroxychloroquine; 1200mg of Hydroxychloroquine (orally; 600mg twice a day (BID)) daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patients free of disease progression	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.	Twelve weeks from starting treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumour Response Rate	Confirmed tumour response rate as assessed by RECIST version 1.1.	Twelve weeks following the 15th and 22nd patients.
Duration of Response	Confirmed duration of response as assessed by RECIST version 1.1.	Through study treatment, an average of 1 year
Overall Survival	Overall Survival	Through study completion, an average of five years
Safety and tolerability	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.	Through study treatment, an average of one year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number of successfully established organoid cultures per patient before and on treatment	The number of successfully established organoid cultures per patient from biopsies of patients with pancreatic cancer being treated with trametinib and hydroxychloroquine before treatment and on treatment.	Through study treatment, an average of one year
Organoid resistance to trametinib and hydroxychloroquine	The number of organoids resistant to trametinib and hydroxychloroquine treatment as measured by proliferation and apoptosis rates.	Through study treatment, an average of one year
Resistance mechanisms and their potential therapies in vitro	A list of potential resistance mechanisms and their potential therapies that can be tested on in vitro organoid cultures.	Through study treatment, an average of one year
Comparison of new methods of multi-omics data integration vs existing models using AUROC	A comparison the performance of new methods of multi-omics data integration against existing models using AUROC (area under the receiver operating characteristic) analysis.	Through study treatment, an average of one year

Collaborators and Investigators

• Sponsor: Cancer Trials Ireland
• Collaborators: Novartis
• Investigators: Principal Investigator: Austin Duffy, Mater Misericordiae University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2023
• Primary Completion (Actual): March 3, 2026
• Study Completion (Actual): March 3, 2026

Study Registration Dates

• First Submitted: July 22, 2022
• First Submitted That Met QC Criteria: August 24, 2022
• First Posted (Actual): August 26, 2022

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 8, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Metastatic refractory; Primary and emerging resistance mechanisms
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Quinolines; Aminoquinolines; Chloroquine; Hydroxychloroquine; trametinib
• Other Study ID Numbers: CTRIAL-IE 20-27; 2021-006276-16 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pseudo-anonymised biological samples will be shared with the University College of Dublin for performance of the translational sub-study throughout the study.
• IPD Sharing Time Frame: Study duration
• IPD Sharing Access Criteria: IPD data will be shared for all patients who provide informed consent to participation in the sub-study.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No