What side effects are associated with this type of intervention?

Common treatments for pancreatic cancer, including ERK1/2 inhibitors like LY3214996 and autophagy inhibitors like Hydroxychloroquine Sulfate, often come with a range of side effects. ERK1/2 inhibitors can cause fatigue, gastrointestinal issues, and skin rashes. Hydroxychloroquine Sulfate is known to cause gastrointestinal disturbances, retinal toxicity, and cardiac issues. Additionally, general treatments for pancreatic cancer, such as chemotherapy, can lead to nausea, vomiting, hair loss, and increased risk of infections due to immunosuppression.

What prior FDA approvals exist?

The FDA has approved several treatments for pancreatic cancer, including targeted therapies and chemotherapy. While specific approvals for ERK1/2 inhibitors like LY3214996 and autophagy inhibitors like Hydroxychloroquine Sulfate are not detailed, other targeted therapies such as sunitinib, which is used for advanced pancreatic neuroendocrine tumors, have been approved. Sunitinib targets multiple receptor tyrosine kinases, showing the FDA's interest in targeted approaches for pancreatic cancer treatment.

What other types of research exist?

Promising novel alternatives for pancreatic cancer treatment in 2024 include: <ol> <li>KRAS G12C Inhibitors: These target a common mutation in pancreatic cancer and have shown efficacy in early trials.</li> <li>PARP Inhibitors: Effective in patients with BRCA mutations, these inhibitors impair DNA repair mechanisms in cancer cells.</li> <li>Immunotherapy Combinations: Combining immune checkpoint inhibitors (e.g., pembrolizumab) with other agents like chemotherapy or targeted therapies to enhance anti-tumor response.</li> <li>Stromal Modulators: Agents like PEGPH20 that target the tumor microenvironment to improve drug delivery and efficacy.</li> <li>Multi-kinase Inhibitors: Drugs like cabozantinib that target multiple pathways involved in tumor growth and metastasis.</li> </ol>

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LY3214996 +/- HCQ for Pancreatic Cancer

Phase 2

Waitlist Available

Led By Brian Wolpin, MD, PHD

Research Sponsored by Kimberly Perez, MD

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Participants must have histologically or cytologically confirmed adenocarcinoma or poorly differentiated carcinoma of the pancreas

Age ≥ 18 years

Must not have

Participants with pancreatic histologies other than adenocarcinoma or poorly differentiated carcinoma, such as neuroendocrine or acinar cell carcinoma

Participants who have received a prior MAPK pathway inhibitor, including but not limited to LY3214996

Timeline

Screening 3 weeks

Treatment Varies

Follow Up overall survival (os) is defined as the time from randomization (or registration) to death due to any cause, or censored at date last known alive up to 34 months

Awards & highlights

No Placebo-Only Group

Summary

This study is evaluating whether a combination of two drugs may help treat pancreatic cancer.

Who is the study for?

Adults with advanced pancreatic cancer who've had 1-2 prior treatments can join this trial. They need to be relatively healthy, able to take oral meds, and have a tumor that can be measured and biopsied. Women of childbearing age and men must use birth control. People with recent other treatments, brain metastases, certain heart issues or infections, pregnant women, those with specific genetic conditions or allergies related to the drugs cannot participate.

What is being tested?

The study is testing if LY3214996 combined with hydroxychloroquine sulfate (HCQ) is safe and works against advanced pancreatic cancer. Participants will receive both medications orally to see how well they work together in treating their cancer.

What are the potential side effects?

Potential side effects may include typical reactions seen with anti-cancer agents such as nausea, fatigue, liver function changes, risk of infection due to bone marrow suppression; specific risks from these drugs are not listed but could align with known effects of similar therapies.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My cancer is a type of pancreatic cancer confirmed by lab tests.

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I am 18 years old or older.

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I am fully active and can carry on all pre-disease activities without restriction.

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I have at least one tumor that can be measured.

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I have had 1 or 2 treatments for metastatic pancreatic cancer.

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I can swallow and keep down pills.

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I am willing and able to have a biopsy of my cancer.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My pancreatic cancer is not adenocarcinoma or poorly differentiated carcinoma.

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I have previously taken medication that targets the MAPK pathway.

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I haven't had chemotherapy, immunotherapy, or experimental treatments in the last 3 weeks.

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I have not had major surgery in the last 4 weeks.

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I do not have brain metastases.

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I am allergic to medications similar to LY3214996 or HCQ.

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I do not have any severe illnesses or social situations that would stop me from following the study's requirements.

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I or someone in my family has a history of long QT syndrome.

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I have a known G6PD deficiency.

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I need to take strong medication that affects liver enzymes during the trial.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ overall survival (os) is defined as the time from randomization (or registration) to death due to any cause, or censored at date last known alive up to 34 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~overall survival (os) is defined as the time from randomization (or registration) to death due to any cause, or censored at date last known alive up to 34 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and overall survival (os) is defined as the time from randomization (or registration) to death due to any cause, or censored at date last known alive up to 34 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Disease control rate (DCR)

Dose Limiting Toxicity-Lead In

Secondary study objectives

Objective response rate (ORR)

Overall survival (OS)

Progression-free survival (PFS)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

4Treatment groups

Experimental Treatment

Group I: Safety Lead-In CohortExperimental Treatment2 Interventions

The research study procedures include screening for eligibility and study treatment. Study treatment will include evaluations, biopsies, and follow up visits. A treatment cycle will be defined as 28 consecutive days. Treatment will be administered on an outpatient basis. Test the safety of study drugs in combination and define dose levels. * LY3214996 * HCQ

Group II: LY3214996-MonotherapyExperimental Treatment1 Intervention

The research study procedures include screening for eligibility and study treatment. Study treatment will include evaluations, biopsies, and follow up visits. A treatment cycle will be defined as 28 consecutive days.Treatment will be administered on an outpatient basis. -LY3214996

Group III: LY3214996 and HCQ CombinationExperimental Treatment2 Interventions

The research study procedures include screening for eligibility and study treatment. Study treatment will include evaluations, biopsies, and follow up visits. A treatment cycle will be defined as 28 consecutive days. Treatment will be administered on an outpatient basis. Combined dosage per determined Lead-In Cohort * LY3214996 * HCQ

Group IV: Cross Over ArmExperimental Treatment2 Interventions

Participants who are enrolled to Arm 2 who experience radiologic disease progression on monotherapy will have the option to cross-over to receive treatment with the combination. Crossover will occur at the treating investigator's discretion following consultation and approval from the overall principal investigator. Combined dosage per determined Lead-In Cohort * LY3214996 * HCQ

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Hydroxychloroquine Sulfate

2015

Completed Phase 4

~1080

LY3214996

2019

Completed Phase 2

~270

0 / 17Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for pancreatic cancer, such as ERK1/2 inhibitors and autophagy inhibitors, work by targeting specific cellular pathways that are crucial for cancer cell survival and proliferation. ERK1/2 inhibitors, like LY3214996, disrupt the ERK pathway, which is essential for cell division and survival, thereby potentially reducing tumor growth. Autophagy inhibitors, such as Hydroxychloroquine Sulfate, block the process by which cancer cells recycle cellular components to survive under stress, leading to cancer cell death. These targeted treatments are particularly important for pancreatic cancer patients because they address the specific dysregulated pathways in pancreatic cancer cells, offering a more precise and potentially effective therapeutic approach.

Inhibition of ERK1/2 in cancer-associated pancreatic stellate cells suppresses cancer-stromal interaction and metastasis.