Trametinib + Hydroxychloroquine for Pancreatic Cancer
(THREAD Trial)
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: University of Utah
Must not be taking: Antineoplastics, Radiotherapy
Disqualifiers: Brain metastases, Retinal vein occlusion, others
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?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.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications. However, you cannot have received certain cancer treatments or investigational therapies within 2 weeks before starting the study treatment.
What data supports the effectiveness of the drug combination of Trametinib and Hydroxychloroquine for pancreatic cancer?
Preclinical studies have shown promising results for the combination of Trametinib and Hydroxychloroquine in treating pancreatic cancer, although these regimens have not been extensively tested in patients. Additionally, Hydroxychloroquine combined with gemcitabine has been effective in increasing surgery rates and showing positive biomarker responses in pancreatic cancer patients.
12345What safety data exists for Hydroxychloroquine and Trametinib in humans?
Hydroxychloroquine (Plaquenil) has been associated with eye problems, including retinal toxicity, which can affect vision. It can also cause rare neuropsychiatric side effects like hallucinations.
678910How is the drug combination of Trametinib and Hydroxychloroquine unique for treating pancreatic cancer?
The combination of Trametinib and Hydroxychloroquine is unique because it targets pancreatic cancer in a novel way by combining a MEK inhibitor (Trametinib) with an autophagy inhibitor (Hydroxychloroquine), and it is being explored as a third-line treatment option when standard treatments are not available.
1231112Eligibility Criteria
This trial is for adults with advanced pancreatic cancer that has spread and isn't eligible for surgery. Participants must have tried two standard treatments or refused them, have measurable disease, be able to provide a biopsy, and have functioning major organs. They should not be pregnant, agree to use effective contraception, and not have certain health conditions like active bleeding or recent major surgery.Inclusion Criteria
I can take care of myself and perform daily activities.
You have enough infection-fighting white blood cells in your body.
I have recovered from previous treatment side effects, or they are minor and stable.
+13 more
Exclusion Criteria
I have not had radiotherapy in the last 2 weeks, except for treating bone metastasis.
I had major surgery less than 3 weeks ago or am still dealing with its side effects.
I have had a major bleeding event in the past.
+6 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Patients receive trametinib and hydroxychloroquine orally on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
28 days per cycle
Follow-up
Participants are monitored for safety and effectiveness after treatment, including the assessment of adverse events.
30 days after last dose
Long-term follow-up
Participants are assessed for response rate to the treatment over an extended period.
5 years
Participant Groups
The study is testing the combination of Trametinib and Hydroxychloroquine in patients with pancreatic cancer. Trametinib blocks enzymes needed for cell growth while Hydroxychloroquine may prevent tumor cells from growing or spreading. The goal is to find the best dose of Hydroxychloroquine that can be given safely with Trametinib.
1Treatment groups
Experimental Treatment
Group I: Treatment (trametinib, hydroxychloroquine)Experimental Treatment2 Interventions
Patients 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.
Hydroxychloroquine is already approved in United States, European Union for the following indications:
๐บ๐ธ Approved in United States as Plaquenil for:
- Malaria
- Rheumatoid Arthritis
- Systemic Lupus Erythematosus
๐ช๐บ Approved in European Union as Plaquenil for:
- Malaria
- Rheumatoid Arthritis
- Systemic Lupus Erythematosus
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of California, San FranciscoSan Francisco, CA
Huntsman Cancer Institute/University of UtahSalt Lake City, UT
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Who Is Running the Clinical Trial?
University of UtahLead Sponsor
Novartis PharmaceuticalsIndustry Sponsor
References
Phase I study of a chloroquine-gemcitabine combination in patients with metastatic or unresectable pancreatic cancer. [2022]Following a previously published pre-clinical validation, this phase I study evaluated the safety, maximum tolerated dose, anti-tumour activity and immune status of a gemcitabine-chloroquine combination as a first- or late-line treatment in patients with metastatic or unresectable pancreatic cancer.
A real-world analysis of trametinib in combination with hydroxychloroquine or CDK4/6 inhibitor as third- or later-line therapy in metastatic pancreatic adenocarcinoma. [2023]There are no standard third-line treatment options for metastatic pancreatic ductal adenocarcinoma (mPDAC). Trametinib in combination with hydroxychloroquine (HCQ) or CDK4/6 inhibitors for pancreatic adenocarcinoma showed promising efficacy in preclinical studies. However, the regimens have not been well examined in patients with mPDAC.
Comparison of FOLFIRINOX vs Gemcitabine Plus Nab-Paclitaxel as First-Line Chemotherapy for Metastatic Pancreatic Ductal Adenocarcinoma. [2023]FOLFIRINOX (leucovorin calcium [folinic acid], fluorouracil, irinotecan hydrochloride, and oxaliplatin) and gemcitabine plus nab-paclitaxel are the 2 common first-line therapies for metastatic adenocarcinoma of the pancreas (mPC), but they have not been directly compared in a clinical trial, and comparative clinical data analyses on their effectiveness are limited.
Encouraging long-term survival following autophagy inhibition using neoadjuvant hydroxychloroquine and gemcitabine for high-risk patients with resectable pancreatic carcinoma. [2023]Preoperative autophagy inhibition with hydroxychloroquine (HCQ) in combination with gemcitabine in pancreatic adenocarcinoma (PDAC) has been shown to be safe and effective in inducing a serum biomarker response and increase resection rates in a previous phase I/II clinical trial. We aimed to analyze the long-term outcomes of preoperative HCQ with gemcitabine for this cohort.
BAYPAN study: a double-blind phase III randomized trial comparing gemcitabine plus sorafenib and gemcitabine plus placebo in patients with advanced pancreatic cancer. [2023]Sorafenib is an oral anticancer agent targeting Ras-dependent signaling and angiogenic pathways. A phase I trial demonstrated that the combination of gemcitabine and sorafenib was well tolerated and had activity in advanced pancreatic cancer (APC) patients. The BAYPAN study was a multicentric, placebo-controlled, double-blind, randomized phase III trial comparing gemcitabine/sorafenib and gemcitabine/placebo in the treatment of APC.
Retinal toxicity secondary to Plaquenil therapy. [2016]Hydroxychloroquine sulfate (Plaquenil; Sanofi-Aventis, Bridgewater, New Jersey) is an antimalarial agent, which is sometimes used for the treatment of certain autoimmune disorders. Its use has been associated with ocular side effects; the most concerning is toxic maculopathy.
Highly Accelerated Onset of Hydroxychloroquine Macular Retinopathy. [2020]Hydroxychloroquine (HCQ, Plaquenil) is often prescribed in lieu of other sulfate antimalarials to treat rheumatologic diseases because of its pharmacologic efficacy and few reported side effects. However, a known potential side effect of HCQ is retinal toxicity.
Retinal toxicity associated with chronic exposure to hydroxychloroquine and its ocular screening. Review. [2022]Hydroxychloroquine sulfate (HCQ, Plaquenil) is an analogue of chloroquine (CQ), an antimalarial agent, used for the treatment of systemic lupus erythematosus, rheumatoid arthritis and other autoimmune disorders. Its use has been associated with severe retinal toxicity, requiring a discontinuation of therapy. Because it presents potential secondary effects including irreversible maculopathy, knowledge of incidence, risk factors, drug toxicity and protocol screening of the patients it represents important data for the ophthalmologists. Thus, it is imperative that rheumatologists, medical internists and ophthalmologists are aware of the toxicity from hydroxychloroquine they should also be careful to minimize its occurrence and effects.
Determination of the stereoisomers of hydroxychloroquine and its major metabolites in plasma and urine following a single oral administration of racemic hydroxychloroquine. [2021]Plaquenil (hydroxychloroquine, HCQ; Sanofi Winthrop Pharmaceuticals, New York, NY) is a stereoisomeric drug administered as a racemic (50: 50) mixture of two isomeric forms--(+) and (-) HCQ. To correlate clinical efficiency accurately with dose, it is necessary to determine the fate of both isomers. This will allow for the optimization of clinical dosing. A method has been developed for the quantitation of (+) and (-) HCQ and its major metabolites, desethylhydroxychloroquine (DHCQ), desethylchloroquine (DCQ), and bisdesethylchloroquine (BDCQ), in plasma and in urine. Application of this method in a preliminary study in four human volunteers is reported. After a single oral dose of 200 mg of Plaquenil, the average enantiomeric ratio of (+) to (-) HCQ was approximately 1 over an 8-hour period. However, the average cumulative 48-hour excretion of HCQ, DHCQ, and DCQ showed stereoselective excretion.
[Hallucinations during treatment with hydrochloroquine]. [2019]We report an unexpected cenesthetic hallucination-type neuropsychiatric side effect with hydrochloroquine (Plaquenil) in a patient treated for an erosive plantar lichen planus.
Gemcitabine plus sorafenib in patients with advanced pancreatic cancer: a phase II trial of the University of Chicago Phase II Consortium. [2022]Sorafenib, an inhibitor of B-raf, VEGFR2, and PDGFR-ฮฒ, has activity against pancreatic cancer in preclinical models. In a phase I trial of gemcitabine plus sorafenib, 57% of pancreatic cancer patients achieved stable disease.
Efficacy of Capecitabine Plus Oxaliplatin Combination Chemotherapy for Advanced Pancreatic Cancer after Failure of First-Line Gemcitabine-Based Therapy. [2022]Second-line chemotherapy in patients with advanced pancreatic ductal adenocarcinoma (PDAC) that progresses following gemcitabine-based treatment has not been established. This study aimed to investigate the efficacy and safety of second-line combination chemotherapy with capecitabine and oxaliplatin (XELOX) in these patients.