PaTcH Trial: A phase 2 study to explore primary and emerging resistance mechanisms in patients with metastatic refractory Pancreatic cancer treated with Trametinib and Hydrochloroquine.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Cancer Trials Ireland

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

27 Jun 2023 → ongoing

Decision date (initial)

2024-06-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Pat Smullen Pancreatic Cancer Fund

External identifiers

EU CT number

2024-513429-21-00

EudraCT number

2021-006276-16

ClinicalTrials.gov

NCT05518110

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenomic, Therapy, Efficacy, Safety

To determine the 12-week progression free survival (PFS) of trametinib and hydroxychloroquine in patients with metastatic refractory pancreatic cancer.

Secondary objectives 6

1. To determine the response rate, duration of response and overall survival in patients with metastatic refractory pancreatic cancer treated with trametinib and hydroxychloroquine.
2. To assess the safety and tolerability of this regimen.
3. To establish patient-derived organoids from biopsies of patients with pancreatic cancer being treated with trametinib and hydroxychloroquine before treatment and on treatment.
4. To assess efficiency of treatment and potential emerging resistance mechanisms in patient-derived organoid cultures from patients with pancreatic cancer treated with trametinib and hydroxychloroquine.
5. To deeply characterise resistance mechanisms and design and test potential rescue therapies in patient-derived organoid cultures from patients with pancreatic cancer treated with trametinib and hydroxychloroquine.
6. To further refine the computational resistance models using new methods of multi-omics data integration.

Conditions and MedDRA coding

Metastatic refractory Pancreatic Cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

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: a. Serum creatinine ≤ 1.5 x ULN. b. Adequate hepatic function defined by: o total bilirubin level ≤ 1.5 × ULN, o 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) c. Hematological eligibility parameters: o Absolute Neutrophil count ≥ 1.5 x 109/L o Platelet count ≥100 x109/L o 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 19

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Anti-tumour efficacy of tx will be primarily measured as 12W PFS: Percentage of patients free of progression at 12W from starting treatment into the study as determined by radiographic disease assessments per RECIST version 1.1. Planned efficacy assessments will occur by CT TAP at baseline, 6W, 12W post starting treatment and then q-8 weekly until disease progression or consent withdrawal.

Secondary endpoints 3

1. Confirmed tumour response rate and duration of response as assessed by RECIST version 1.1.
2. Overall survival
3. To evaluate 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Cancer Trials Ireland

Sponsor organisation

Cancer Trials Ireland

Address

Rcsi House, 121 Saint Stephen's Green 121 Saint Stephen's Green

City

Dublin 2

Postcode

D02 H903

Country

Ireland

Scientific contact point

Organisation

Cancer Trials Ireland

Contact name

Chief Operations Officer

Public contact point

Organisation

Cancer Trials Ireland

Contact name

Chief Operations Officer

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications