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

NCT05518110 | Terminated Phase 2

• 2 other identifiers: CTRIAL-IE 20-272021-006276-16
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

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.

Conditions

Pancreatic Cancer

Keywords

Metastatic refractory; Primary and emerging resistance mechanisms

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Tumour Response Rate

  Twelve weeks following the 15th and 22nd patients.

• Duration of Response

  Through study treatment, an average of 1 year

• Overall Survival

  Through study completion, an average of five years

• Safety and tolerability

  Through study treatment, an average of one year

Other Outcomes (4)

• The number of successfully established organoid cultures per patient before and on treatment

  Through study treatment, an average of one year

• Organoid resistance to trametinib and hydroxychloroquine

  Through study treatment, an average of one year

• Resistance mechanisms and their potential therapies in vitro

  Through study treatment, an average of one year

Study Arms (1)

PaTcH

EXPERIMENTAL

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; Drug: Hydroxychloroquine

Interventions

Trametinib DRUG

2mg of Trametinib (orally) daily.

PaTcH

Hydroxychloroquine DRUG

1200mg of Hydroxychloroquine (orally; 600mg twice a day (BID)) daily.

PaTcH

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have pathologically confirmed advanced metastatic pancreatic adenocarcinoma or poorly differentiated pancreatic adenocarcinoma that is amenable to tumour biopsy.
• Patients have received at least one line of systemic therapy for metastatic disease and not be amenable to surgical resection.
• Patients must have measurable disease by RECIST 1.1 criteria.
• Age ≥18 years.
• ECOG performance status ≤ 1
• Patients must have normal organ and marrow function as defined below:
• Serum creatinine ≤ 1.5 x ULN.
• 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)
• Hematological eligibility parameters:
• Absolute Neutrophil count ≥ 1.5 x 109/L
• Platelet count ≥100 x109/L
• Hemoglobin ≥ 9 g/dL
• Ability of subject to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• 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.
• Prior treatment with a MEK inhibitor
• Known history of testing positive for Human Immunodeficiency Virus (HIV) or known acquired immunodeficiency syndrome.
• Any significant disease that, in the opinion of the investigator, may impair the patient's tolerance of study treatment.
• Patients who are receiving any other investigational agents within 28 days before start of study treatment.
• Prior organ transplantation including allogenic stem-cell transplantation.
• Patients with known central nervous system metastases.
• Active uncontrolled infection, requiring systemic therapy.
• 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.
• Severe left ventricular dysfunction as defined by ejection fraction \< 45%
• 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.
• Known maculopathy of the eye
• 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)
• Screening corrected QT interval by Fridericia (QTcF) \> 500 msec
• Pregnant women and breastfeeding mothers are excluded due to unknown impact on embryos or infants

Sponsors & Collaborators

• Cancer Trials Ireland: lead
• Novartis: collaborator

Study Sites (2)

Mater Misericordiae University Hospital

Dublin, D07 R2WY, Ireland

Location

St Vincent's University Hospital

Dublin, DO4 T6F4, Ireland

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

trametinib; Hydroxychloroquine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Austin Duffy

  Mater Misericordiae University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2022
• First Posted: August 26, 2022
• Study Start: May 31, 2023
• Primary Completion: March 3, 2026
• Study Completion: March 3, 2026
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Study duration
• Access Criteria: IPD data will be shared for all patients who provide informed consent to participation in the sub-study.

Locations

IE (2)