25 Participants Needed

Trametinib + Hydroxychloroquine for Pancreatic Cancer

(THREAD Trial)

Recruiting at 1 trial location
SS
Overseen BySusan Sharry
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

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 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.12345

How 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.678910

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.67101112

Who Is on the Research Team?

CK

Conan G. Kinsey

Principal Investigator

Huntsman Cancer Institute/ University of Utah

Are You a Good Fit for This Trial?

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.
See 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.
See 6 more

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

  • Hydroxychloroquine
  • Trametinib
Trial Overview 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.
How Is the Trial Designed?
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:

🇺🇸
Approved in United States as Plaquenil for:
  • Malaria
  • Rheumatoid Arthritis
  • Systemic Lupus Erythematosus
🇪🇺
Approved in European Union as Plaquenil for:
  • Malaria
  • Rheumatoid Arthritis
  • Systemic Lupus Erythematosus

Find a Clinic Near You

Who Is Running the Clinical Trial?

University of Utah

Lead Sponsor

Trials
1,169
Recruited
1,623,000+

Novartis Pharmaceuticals

Industry Sponsor

Trials
2,963
Recruited
4,275,000+
Founded
1996
Headquarters
Basel, Switzerland
Known For
Precision medicine
Top Products
Gleevec, Cosentyx, Entresto, Kisqali
Dr. Vas Narasimhan profile image

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye profile image

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Published Research Related to This Trial

The combination of gemcitabine and chloroquine was well tolerated in a phase I study involving nine patients with metastatic pancreatic cancer, with no dose-limiting toxicities observed.
Three patients showed a partial response to the treatment, and the median overall survival was 7.6 months, suggesting that this combination may enhance the effectiveness of chemotherapy and warrants further investigation.
Phase I study of a chloroquine-gemcitabine combination in patients with metastatic or unresectable pancreatic cancer.Samaras, P., Tusup, M., Nguyen-Kim, TDL., et al.[2022]
In a study of 13 patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) receiving trametinib combined with hydroxychloroquine or CDK4/6 inhibitors, only one patient achieved stable disease, indicating limited efficacy of this treatment regimen.
The median overall survival for patients treated with trametinib plus hydroxychloroquine was 4.2 months, and 4.7 months for those treated with CDK4/6 inhibitors, with 50% of patients experiencing significant adverse events, suggesting safety concerns alongside limited effectiveness.
A real-world analysis of trametinib in combination with hydroxychloroquine or CDK4/6 inhibitor as third- or later-line therapy in metastatic pancreatic adenocarcinoma.Tang, H., Ge, Y., You, T., et al.[2023]
In a study of 1102 patients with metastatic pancreatic cancer, FOLFIRINOX treatment resulted in a median overall survival of 9.27 months, significantly longer than the 6.87 months observed with gemcitabine plus nab-paclitaxel (P < 0.001).
Patients receiving FOLFIRINOX also experienced 17.3% fewer posttreatment hospitalizations and 20% lower posttreatment costs compared to those treated with gemcitabine plus nab-paclitaxel, indicating better safety and efficacy.
Comparison of FOLFIRINOX vs Gemcitabine Plus Nab-Paclitaxel as First-Line Chemotherapy for Metastatic Pancreatic Ductal Adenocarcinoma.Klein-Brill, A., Amar-Farkash, S., Lawrence, G., et al.[2023]

Citations

Phase I study of a chloroquine-gemcitabine combination in patients with metastatic or unresectable pancreatic cancer. [2022]
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]
Comparison of FOLFIRINOX vs Gemcitabine Plus Nab-Paclitaxel as First-Line Chemotherapy for Metastatic Pancreatic Ductal Adenocarcinoma. [2023]
Encouraging long-term survival following autophagy inhibition using neoadjuvant hydroxychloroquine and gemcitabine for high-risk patients with resectable pancreatic carcinoma. [2023]
BAYPAN study: a double-blind phase III randomized trial comparing gemcitabine plus sorafenib and gemcitabine plus placebo in patients with advanced pancreatic cancer. [2023]
Retinal toxicity secondary to Plaquenil therapy. [2016]
Highly Accelerated Onset of Hydroxychloroquine Macular Retinopathy. [2020]
Retinal toxicity associated with chronic exposure to hydroxychloroquine and its ocular screening. Review. [2022]
Determination of the stereoisomers of hydroxychloroquine and its major metabolites in plasma and urine following a single oral administration of racemic hydroxychloroquine. [2021]
[Hallucinations during treatment with hydrochloroquine]. [2019]
11.United Statespubmed.ncbi.nlm.nih.gov
Gemcitabine plus sorafenib in patients with advanced pancreatic cancer: a phase II trial of the University of Chicago Phase II Consortium. [2022]
12.Korea (South)pubmed.ncbi.nlm.nih.gov
Efficacy of Capecitabine Plus Oxaliplatin Combination Chemotherapy for Advanced Pancreatic Cancer after Failure of First-Line Gemcitabine-Based Therapy. [2022]
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