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Metastatic Pancreatic CarcinomaPhase 1THREADNCT03825289

Trametinib and Hydroxychloroquine in Treating Patients With Pancreatic Cancer

A Phase 1 study testing Hydroxychloroquine and Trametinib in people with Metastatic Pancreatic Carcinoma and Stage II Pancreatic Cancer, run by University of Utah at 2 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This phase I trial studies the sides effects and best dose of hydroxychloroquine when given together with trametinib in treating patients with pancreatic cancer that has spread to nearby tissue, lymph nodes or other places in the body and cannot be removed by surgery. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Hydroxychloroquine and Trametinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
2 sitesUnited States
Study dates
30 Jan 2019to 3 Aug 2025
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female subject aged ≥ 18 years.
  • Subject with histologically confirmed metastatic or locally advanced, unresectable pancreatic carcinoma
  • Subject is willing to provide a baseline biopsy.
  • EXPANSION COHORT ONLY: Subject must have progressed during or after two standard of care lines of treatment or refused standard of care options.
  • Subject must have computed tomography (CT) measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
  • Subject must be able and willing to undergo disease assessment while on study and afterwards, if removed for reason other than progression
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  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Adequate organ function as defined as:
  • Hematologic:
  • Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
  • Platelet count >= 100 x 10^9/L
  • Hemoglobin >= 9 g/dL
  • Hepatic:
  • Total bilirubin level =< 1.5 x the upper limit of normal (ULN) range
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels =< 3 x ULN. Patients with liver metastases will be allowed to enroll with AST and ALT levels =< 5 x ULN
  • Renal:
  • Estimated creatinine clearance >= 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method)
  • Negative serum or urine pregnancy test at screening for women of childbearing potential
  • Highly effective contraception for both male and female subjects throughout the study and for at least 4 months after last study treatment administration
  • Recovery to baseline or =< grade 1 Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0 from toxicities related to any prior treatments, unless adverse event (AE)(s) are clinically nonsignificant and/or stable on supportive therapy
  • Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines

Who cannot join

  • Subject who have received systemic antineoplastic therapy (including unconjugated therapeutic antibodies and toxin immunoconjugates) or any investigational therapy within 2 weeks or within 5 half-lives of the investigational therapy prior to starting study treatment, whichever is shorter.
  • Subject who have received radiotherapy within 2 weeks prior to the first dose of study treatment. Localized radiation therapy for the treatment of symptomatic bone metastasis is allowed during that timeframe
  • Subjects who have undergone major surgery =< 3 weeks prior to starting study drug or who have not recovered from side effects of such procedure
  • Patients with multiple primary malignancies may be enrolled if non-pancreatic ductal adenocarcinoma (PDAC) tumor(s) does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen as determined by treating investigator and do not require active treatment
  • Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before first dose of study treatment. Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of first dose of study treatment
  • 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)
Show all 26Show fewer
  • History of active major bleeding.
  • Patients whom thromboembolic prophylaxis is medically contraindicated per the treating investigator's assessment.
  • Current evidence of uncontrolled, significant intercurrent illness including, but not limited to, the following conditions:
  • Cardiovascular disorders:
  • Congestive heart failure New York Heart Association class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias.
  • Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (eg, deep venous thrombosis, pulmonary embolism) within 3 months before first dose. The presence of an asymptomatic portal vein thrombosis will not preclude study participation.
  • History of glucose-6-phosphate dehydrogenase (G6PD) deficiency
  • History of seizures
  • Patients who are planning on embarking on a new strenuous exercise regimen after first dose of study treatment. Muscular activities, such as strenuous exercise, that can result in significant increases in plasma creatine kinase (CK) levels should be avoided while on study treatment
  • Patients who have neuromuscular disorders that are associated with elevated CK (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy)
  • Impairment of gastrointestinal function or gastrointestinal disease (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection that under the judgment of the principal investigator [PI] may impair absorption of study drugs)
  • Any other condition that would, in the Investigator?s judgment, contraindicate the patient?s participation in the clinical study due to safety concerns or compliance with clinical study procedures, e.g., infection/inflammation, intestinal obstruction, unable to swallow medication.(patients may not receive drug through a feeding tube), social/ psychological issues, etc
  • Screening corrected QT interval by Fridericia (QTcF) > 500 msec
  • Known human immunodeficiency virus (HIV), unless patient is on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
  • Known chronic hepatitis B virus, unless hepatitis B virus (HBV) viral load is undetectable
  • Known history of hepatitis C virus (HCV) infection, unless treated and cured; for patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
  • Medical, psychiatric, cognitive or other conditions that may compromise the patient's ability to understand the patient information, give informed consent, comply with the study protocol or complete the study
  • Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test
  • Sexually active males who are not willing to use a condom during intercourse while taking the drug and for 4 months after stopping treatment. A condom is also required to be used by vasectomized men in order to prevent delivery of the drug via seminal fluid
  • Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (National Cancer institute [NCI] CTCAE v5.0 grade >= 3)

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Huntsman Cancer Institute/University of Utah

    Salt Lake City, Utah, 84112

  • University of California, San Francisco

    San Francisco, California, 94143

Other trials in United States

About this study

Official title: THREAD: A Phase I Trial of Trametinib and Hydroxychloroquine in Patients With Advanced Pancreatic Cancer

This phase I trial studies the sides effects and best dose of hydroxychloroquine when given together with trametinib in treating patients with pancreatic cancer that has spread to nearby tissue, lymph nodes or other places in the body and cannot be removed by surgery. Trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as hydroxychloroquine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving trametinib together with hydroxychloroquine may work better in treating patients with pancreatic cancer.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the recommended phase II dose of hydroxychloroquine in combination with trametinib as assessed by the occurrence of dose-limiting toxicities (DLTs).
Medical subject headings
Pancreatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT03825289
Study groupRoleWhat they receive
Treatment (trametinib, hydroxychloroquine)ExperimentalPatients receive trametinib PO QD on days 1-28 and hydroxychloroquine PO QD or BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Hydroxychloroquine; Drug: Trametinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Rate of dose-limiting toxicities during the DLT assessment window.

    To determine the recommended phase II dose (RP2D) hydroxychloroquine in combination with trametinib.

    Measured: At 28 days

Secondary outcomes (2)

  1. Incidence of adverse events (AEs) for the duration of study treatment

    To assess the safety of the combination of trametinib and hydroxychloroquine

    Measured: 30 days after last dose

  2. Response Rate

    To assess the efficacy of the combination of trametinib and hydroxychloroquine

    Measured: 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Jan 2019
  2. Study start30 Jan 2019
  3. Primary completion15 Jan 2025
  4. Study completion3 Aug 2025

Why it stopped: Lack of Funding

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03825289
Sponsor's protocol ID
HCI116898
Acronym
THREAD
Status last verified
May 2026
First submitted
30 Jan 2019
Last updated
14 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin. 2017 Jan;67(1):7-30. doi: 10.3322/caac.21387. Epub 2017 Jan 5.

    PubMed 28055103

  • Kleeff J, Korc M, Apte M, La Vecchia C, Johnson CD, Biankin AV, Neale RE, Tempero M, Tuveson DA, Hruban RH, Neoptolemos JP. Pancreatic cancer. Nat Rev Dis Primers. 2016 Apr 21;2:16022. doi: 10.1038/nrdp.2016.22.

    PubMed 27158978

  • Hidalgo M, Cascinu S, Kleeff J, Labianca R, Lohr JM, Neoptolemos J, Real FX, Van Laethem JL, Heinemann V. Addressing the challenges of pancreatic cancer: future directions for improving outcomes. Pancreatology. 2015 Jan-Feb;15(1):8-18. doi: 10.1016/j.pan.2014.10.001. Epub 2014 Oct 17.

    PubMed 25547205

  • Collisson EA, Trejo CL, Silva JM, Gu S, Korkola JE, Heiser LM, Charles RP, Rabinovich BA, Hann B, Dankort D, Spellman PT, Phillips WA, Gray JW, McMahon M. A central role for RAF-->MEK-->ERK signaling in the genesis of pancreatic ductal adenocarcinoma. Cancer Discov. 2012 Aug;2(8):685-93. doi: 10.1158/2159-8290.CD-11-0347. Epub 2012 May 24.

    PubMed 22628411

  • Infante JR, Somer BG, Park JO, Li CP, Scheulen ME, Kasubhai SM, Oh DY, Liu Y, Redhu S, Steplewski K, Le N. A randomised, double-blind, placebo-controlled trial of trametinib, an oral MEK inhibitor, in combination with gemcitabine for patients with untreated metastatic adenocarcinoma of the pancreas. Eur J Cancer. 2014 Aug;50(12):2072-81. doi: 10.1016/j.ejca.2014.04.024. Epub 2014 Jun 7.

    PubMed 24915778

  • Kasuga A, Nakagawa K, Nagashima F, Shimizu T, Naruge D, Nishina S, Kitamura H, Kurata T, Takasu A, Fujisaka Y, Okamoto W, Nishimura Y, Mukaiyama A, Matsushita H, Furuse J. A phase I/Ib study of trametinib (GSK1120212) alone and in combination with gemcitabine in Japanese patients with advanced solid tumors. Invest New Drugs. 2015 Oct;33(5):1058-67. doi: 10.1007/s10637-015-0270-2. Epub 2015 Aug 12.

    PubMed 26259955

  • Kinsey CG, Camolotto SA, Boespflug AM, Guillen KP, Foth M, Truong A, Schuman SS, Shea JE, Seipp MT, Yap JT, Burrell LD, Lum DH, Whisenant JR, Gilcrease GW 3rd, Cavalieri CC, Rehbein KM, Cutler SL, Affolter KE, Welm AL, Welm BE, Scaife CL, Snyder EL, McMahon M. Protective autophagy elicited by RAF-->MEK-->ERK inhibition suggests a treatment strategy for RAS-driven cancers. Nat Med. 2019 Apr;25(4):620-627. doi: 10.1038/s41591-019-0367-9. Epub 2019 Mar 4.

    PubMed 30833748

  • Rodriguez-Viciana P, Tetsu O, Oda K, Okada J, Rauen K, McCormick F. Cancer targets in the Ras pathway. Cold Spring Harb Symp Quant Biol. 2005;70:461-7. doi: 10.1101/sqb.2005.70.044.

    PubMed 16869784

  • Young A, Lyons J, Miller AL, Phan VT, Alarcon IR, McCormick F. Ras signaling and therapies. Adv Cancer Res. 2009;102:1-17. doi: 10.1016/S0065-230X(09)02001-6.

    PubMed 19595305

  • Kim KB, Kefford R, Pavlick AC, Infante JR, Ribas A, Sosman JA, Fecher LA, Millward M, McArthur GA, Hwu P, Gonzalez R, Ott PA, Long GV, Gardner OS, Ouellet D, Xu Y, DeMarini DJ, Le NT, Patel K, Lewis KD. Phase II study of the MEK1/MEK2 inhibitor Trametinib in patients with metastatic BRAF-mutant cutaneous melanoma previously treated with or without a BRAF inhibitor. J Clin Oncol. 2013 Feb 1;31(4):482-9. doi: 10.1200/JCO.2012.43.5966. Epub 2012 Dec 17.

    PubMed 23248257

  • Gysin S, Lee SH, Dean NM, McMahon M. Pharmacologic inhibition of RAF-->MEK-->ERK signaling elicits pancreatic cancer cell cycle arrest through induced expression of p27Kip1. Cancer Res. 2005 Jun 1;65(11):4870-80. doi: 10.1158/0008-5472.CAN-04-2848.

    PubMed 15930308

  • Gysin S, Paquette J, McMahon M. Analysis of mRNA profiles after MEK1/2 inhibition in human pancreatic cancer cell lines reveals pathways involved in drug sensitivity. Mol Cancer Res. 2012 Dec;10(12):1607-19. doi: 10.1158/1541-7786.MCR-12-0188. Epub 2012 Jul 25.

    PubMed 22833572

  • Awasthi N, Zhang C, Schwarz AM, Hinz S, Wang C, Williams NS, Schwarz MA, Schwarz RE. Comparative benefits of Nab-paclitaxel over gemcitabine or polysorbate-based docetaxel in experimental pancreatic cancer. Carcinogenesis. 2013 Oct;34(10):2361-9. doi: 10.1093/carcin/bgt227. Epub 2013 Jun 26.

    PubMed 23803690

  • Chew HK, Wun T, Harvey D, Zhou H, White RH. Incidence of venous thromboembolism and its effect on survival among patients with common cancers. Arch Intern Med. 2006 Feb 27;166(4):458-64. doi: 10.1001/archinte.166.4.458.

    PubMed 16505267

  • Larsen AC, Dabrowski T, Frokjaer JB, Fisker RV, Iyer VV, Moller BK, Kristensen SR, Thorlacius-Ussing O. Prevalence of venous thromboembolism at diagnosis of upper gastrointestinal cancer. Br J Surg. 2014 Feb;101(3):246-53. doi: 10.1002/bjs.9353. Epub 2014 Jan 20.

    PubMed 24446107

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Hydroxychloroquine and Trametinib in people with Metastatic Pancreatic Carcinoma and Stage II Pancreatic Cancer, run by University of Utah at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 14 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Lack of Funding). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Rate of dose-limiting toxicities during the DLT assessment window. (time frame: At 28 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03825289, which also lists 24 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2026.

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