Clinical Trials /

LY3214996 +/- HCQ in Pancreatic Cancer

NCT04386057

Description:

This study is evaluating the safety and efficacy of combining the study drug LY3214996 with hydroxychloroquine sulfate (HCQ) in patients with advanced pancreatic cancer.

Related Conditions:
  • Pancreatic Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: LY3214996 +/- HCQ in Pancreatic Cancer
  • Official Title: Phase II Trial of ERK Inhibition Alone and in Combination With Autophagy Inhibition in Patients With Metastatic Pancreatic Cancer

Clinical Trial IDs

  • ORG STUDY ID: 19-529
  • NCT ID: NCT04386057

Conditions

  • Pancreatic Cancer
  • Advanced Cancer

Interventions

DrugSynonymsArms
Hydroxychloroquine SulfatePlaquenil®), HCQCross Over Arm
LY3214996Cross Over Arm

Purpose

This study is evaluating the safety and efficacy of combining the study drug LY3214996 with hydroxychloroquine sulfate (HCQ) in patients with advanced pancreatic cancer.

Detailed Description

      -  This is an open label, randomized, two arm, phase II with safety lead- in study
           exploring the anti-tumor activity of the extracellular signal-regulated kinase (ERK)
           inhibitor LY3214996 with and without hydroxychloroquine (HCQ) in patients with advanced
           pancreatic cancer.

        -  The research study procedures include screening for eligibility and study treatment
           including evaluations and follow up visits.

             -  The safety lead-in will test the safety of a combination of investigational drugs
                and also try to define appropriate dosage. The names of the study drugs involved in
                this study are:

                  -  LY3214996

                  -  Hydroxychloroquine Sulfate (HCQ)

             -  Following completion of a brief combination treatment safety lead-in cohort,
                participants will be randomized 1:1 for enrollment to one of two treatment arms:

                  -  Arm 1: receiving combination treatment with LY3214996 and HCQ

                  -  Arm 2: receiving monotherapy treatment with LY3214996

      It is expected that about 52 people will take part in this research study

      The U.S. Food and Drug Administration (FDA) has not approved LY3214996 as a treatment for any
      disease.

      The U.S. Food and Drug Administration (FDA) has not approved HCQ for your specific disease
      but it has been approved for other uses.
    

Trial Arms

NameTypeDescriptionInterventions
Safety Lead-In CohortExperimentalThe 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
  • Hydroxychloroquine Sulfate
  • LY3214996
LY3214996 and HCQ CombinationExperimentalThe 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
  • Hydroxychloroquine Sulfate
  • LY3214996
LY3214996-MonotherapyExperimentalThe 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
  • LY3214996
Cross Over ArmExperimentalParticipants 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
  • Hydroxychloroquine Sulfate
  • LY3214996

Eligibility Criteria

        Inclusion Criteria:

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

          -  Age ≥ 18 years.

          -  ECOG performance status ≤ 1

          -  Participants must have measurable disease, defined as at least one lesion that can be
             accurately measured in at least one dimension (longest diameter to be recorded for
             nonnodal lesions and short axis for nodal lesions) as ≥ 20 mm with conventional
             techniques or as ≥ 10 mm with spiral CT scan, MRI, or calipers by clinical exam.

          -  Participants must have received at least one but no more than two prior lines of
             systemic therapy for metastatic pancreatic cancer. Perioperative treatment
             (chemotherapy and/or radiation) is not considered a prior line of therapy.

          -  Participants must have adequate organ and marrow function as defined below:

               -  Absolute Neutrophil Count ≥ 1,500/mcL

               -  Platelet Count ≥ 100,000/mcL

               -  Total Bilirubin ≤ 1.5 × institutional upper limit of normal (ULN)

               -  AST (SGOT) / ALT(SGPT) ≤ 2.5 × institutional ULN, OR

               -  AST (SGOT) / ALT (SGPT) ≤ 5 × institutional ULN if elevation is a result of
                  metastases

               -  Creatinine ≤ 1.5 × institutional ULN, OR

               -  Creatinine Clearance ≥ 60 mL/min/1.73 m2 for participants with creatinine levels
                  above 1.5 × institutional normal (calculated via the Cockcroft-Gault equation)

          -  The effects of LY3214996 or HCQ on the developing human fetus are unknown. For this
             reason and because anti-cancer agents are known to be teratogenic, women of child
             bearing potential and men must agree to use adequate contraception (hormonal or
             barrier method of birth control; abstinence) prior to study entry and for the duration
             of study participation. Should a woman become pregnant or suspect she is pregnant
             while she or her partner is participating in this study, she should inform her
             treating physician immediately. Men treated or enrolled on this protocol must also
             agree to use adequate contraception prior to the study, for the duration of study
             participation, and 6 months after completion of LY3214996 or HCQ administration.

          -  Ability to understand and the willingness to sign a written informed consent document.

          -  Ability to swallow and retain oral medication

          -  Baseline QTcB of ≤ 470 msec on screening EKG.

          -  Participants must be able and willing to undergo the pre-treatment biopsy procedure,
             and have a cancer site amenable to biopsy.

        Exclusion Criteria:

          -  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.

          -  Participants who have had systemic chemotherapy, other investigational therapy, or
             immunotherapy within 3 weeks prior to the first dose of study medication.

          -  Participants who have received oral tyrosine kinase inhibitors (TKIs) within 5
             half-lives of the first dose of study medication.

          -  Participants who have received radiation therapy within 2 weeks prior to the first
             dose of study medication.

          -  Participants who have had major surgery within 4 weeks prior to the first dose of
             study medication.

          -  Participants with known brain metastases should be excluded from this clinical trial
             because of their poor prognosis and because they often develop progressive neurologic
             dysfunction that would confound the evaluation of neurologic and other adverse events.

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to LY3214996 or HCQ. Individuals with a history of a different malignancy
             are ineligible with the following exceptions: individuals who have been treated and
             are disease-free for a minimum of 3 years prior to study enrollment, or individuals
             who are deemed by the treating investigator to be at low risk for disease recurrence.
             Additionally, individuals with the following cancers are eligible if diagnosed and
             curatively treated within the past 3 years: basal or squamous cell carcinomas of the
             skin, and breast or cervical carcinomas in situ.

          -  Uncontrolled intercurrent illness including, but not limited to: ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  Pregnant women are excluded from this study because LY3214996 and HCQ are agents with
             the potential for teratogenic or abortifacient effects. Because there is an unknown
             but potential risk for adverse events in nursing infants secondary to treatment of the
             mother with LY3214996 or HCQ, breastfeeding should be discontinued if the mother is
             treated with LY3214996 or HCQ. A negative serum pregnancy test is required for women
             of childbearing potential prior to the first dose of study medication.

          -  Participants who are known to be seropositive for human immunodeficiency virus (HIV)
             or hepatitis B or C.

          -  Participants with a history or findings of central or branch retinal artery or venous
             occlusion with significant vision loss, or other retinal diseases causing visual
             impairment or would likely cause visual impairment over the time period of the study,
             as assessed by an ophthalmologist.

          -  Participants with a known personal or family history of long QT syndrome.

          -  Participants with known glucose-6-phosphate dehydrogenase (G6PD) deficiency.

          -  Participants who are known at the time of trial enrollment to require concomitant
             treatment with strong CYP3A4 inhibitors or inducers. Because the lists of these agents
             are constantly changing, it is important to regularly consult a frequently updated
             medical reference.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Disease control rate (DCR)
Time Frame:28 Months
Safety Issue:
Description:Anti-tumor activity will be measured via disease control rate (DCR), which will be defined as the proportion of patients with complete response (CR), partial response (PR) or stable disease (SD) that persists for ≥ 4 months.

Secondary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:28 Months
Safety Issue:
Description:Objective response rate (ORR)
Measure:Progression-free survival (PFS)
Time Frame:time from randomization (or registration) to the earlier of progression or death due to any cause. Participants alive without disease progression are censored at date of last disease evaluation up to 28 Months
Safety Issue:
Description:Progression-free survival (PFS)
Measure:Overall survival (OS)
Time Frame: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
Safety Issue:
Description:Kaplan and Meier to assess Overall survival (OS)

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Brian Wolpin, MD, MPH

Trial Keywords

  • Pancreatic Cancer
  • Advanced Cancer
  • Extracellular Signal-Regulated Kinases
  • Cell Growth Inhibitors

Last Updated

May 10, 2020