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

NCT ID: NCT05518110

Last Updated: 2024-09-26

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-05-31
• Study Completion Date: 2026-06-30

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.

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.

Conditions

Pancreatic Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Trametinib

Intervention Type: DRUG

2mg of Trametinib (orally) daily.

Hydroxychloroquine

Intervention Type: DRUG

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

Interventions

Trametinib

2mg of Trametinib (orally) daily.

Intervention Type: DRUG

Hydroxychloroquine

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis

INDUSTRY

Sponsor Role: collaborator

Cancer Trials Ireland

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Austin Duffy

Role: PRINCIPAL_INVESTIGATOR

Mater Misericordiae University Hospital

Locations

Mater Misericordiae University Hospital

Dublin, , Ireland

Site Status: RECRUITING

St Vincent's University Hospital

Dublin, , Ireland

Site Status: RECRUITING

Countries

Ireland

Central Contacts

Cancer Trials Ireland

Role: CONTACT

info@cancertrials.ie

+353 (0) 1 6677211

Facility Contacts

Austin Duffy

Role: primary

Ray McDermott

Role: primary

Other Identifiers

2021-006276-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CTRIAL-IE 20-27

Identifier Type: -

Identifier Source: org_study_id