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MC0748, Phase I/II Study of LY2090314 and Gemcitabine or FOLFOX in Untreated, Metastatic Pancreatic Cancer Patients With Metastases Amenable to Biopsy.


Phase 1/Phase 2
18 Years
N/A
Not Enrolling
Both
Duct Cell Adenocarcinoma of the Pancreas, Stage IV Pancreatic Cancer

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Trial Information

MC0748, Phase I/II Study of LY2090314 and Gemcitabine or FOLFOX in Untreated, Metastatic Pancreatic Cancer Patients With Metastases Amenable to Biopsy.


PRIMARY OBJECTIVES:

I. To determine the LY2090314 dose which results in significant inhibition of the biologic
target, glycogen synthase kinase-3 beta (GSK-3β), when administered with gemcitabine (Cohort
I) or FOLFOX (Cohort II) chemotherapy.

SECONDARY OBJECTIVES:

I. To assess clinical activity in the two cohorts as measured by 6-month survival, overall
survival, progression-free survival, confirmed response rate, and toxicity.

TERTIARY OBJECTIVES:

I. Correlate the relationship between GSK-3 inhibition and clinical activity. II. Detect
GSK-3 inhibition in tumor and surrogate specimens (peripheral blood mononuclear cells
[PBMCs]) and compare between observed GSK-3 inhibition among the specimens.

III. Blood will be collected for banking of plasma, serum and buffy coat. IV. Plasma samples
will be collected for pharmacokinetic (PK) analyses

OUTLINE: This is a phase I study followed by a phase II study.

COHORT I: Patients receive LY2090314 intravenously (IV) over 60 minutes on days 0, 8, and 15
of course 1 and on days 1, 8, and 15 of all subsequent courses. Patients also receive
gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Treatment repeats every
28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

COHORT II: Patients receive LY2090314 IV over 60 minutes on days 0 and 15 of course 1 and on
days 1 and 15 of all subsequent courses. Patients also receive FOLFOX chemotherapy
comprising leucovorin calcium IV over 2 hours, fluorouracil IV continuously over 46 hours,
and oxaliplatin IV over 2 hours on days 1and 15. Treatment repeats every 28 days for up to 2
years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.


Inclusion Criteria:



- Histologically or cytologically confirmed adenocarcinoma of the pancreas (ductal or
undifferentiated); Note: If primary previously biopsied, tissue for diagnosis from
metastasis is not required and clinical staging is permitted

- Metastatic pancreatic cancer with metastases amenable to biopsy

- Measurable disease; NOTE: For patients having lesions measuring at least 1 cm to less
than 2 cm must use spiral computed tomography (CT) imaging for both pre- and
post-treatment tumor assessments

- Willingness to provide tissue and blood samples for research purposes

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1

- Absolute neutrophil count (ANC) >= 1500 cell/uL

- Platelet (PLT) >= 100,000 cells/uL

- Total bilirubin < 1.5 x upper normal limit (UNL) (patients may be stented)

- Serum glutamic oxaloacetic transaminase (SGOT)(aspartate aminotransferase [AST]) =< 3
x UNL

- Creatinine < 1.5 x UNL

- Negative serum pregnancy test done =< 7 days prior to registration, for women of
childbearing potential only

- Life expectancy > 12 weeks

- Provide informed written consent

- Willing to return to Mayo Clinic enrolling institution for follow-up

- Agrees to use a reliable method of birth control, as determined by the patient and
his or her health-care team, during the study and for 3 months following the last
dose of study treatment; NOTE: This applies to both male and female patients of
reproductive potential

Exclusion Criteria:

- History of islet cell, acinar cell, or cystadenocarcinomas

- Prior cytotoxic chemotherapy for metastatic disease; exceptions:

- For Cohort I, prior leucovorin calcium, fluorouracil, irinotecan hydrochloride,
and oxaliplatin (FOLFIRINOX) is allowed

- For Cohort II, prior gemcitabine is allowed

- Any of the following prior treatments:

- Prior adjuvant chemotherapy for completely resected disease or chemoradiotherapy
for locally advanced disease =< 180 days prior to registration; Note:
Treatment-related toxicities must be resolved

- Gemcitabine or 5-fluorouracil used as either a radiosensitizer or as maintenance
therapy =< 180 days prior to registration; Note: Treatment-related toxicities
must be resolved

- Radiation therapy < 28 days prior to registration

- Immunotherapy < 28 days prior to registration

- Biologic therapy < 28 days prior to study registration

- Major surgery =< 28 days prior to registration

- Any of the following because this study involves an investigational agent whose
genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are
unknown:

- Pregnant women

- Nursing women

- Men or women of childbearing potential who are unwilling to employ adequate
contraception

- Co-morbid systemic illnesses or other severe concurrent disease which, in the
judgment of the investigator, would make the patient inappropriate for entry into
this study or interfere significantly with the proper assessment of safety and
toxicity of the prescribed regimens

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, or psychiatric illness/social situations that would limit compliance with
study requirements

- Cardiac issues consisting of either symptomatic congestive heart failure (New York
Heart Association class II or higher) unstable angina pectoris, and/or myocardial
infarction =<180 days prior to registration; cardiac arrhythmia (which is symptomatic
or requires treatment) including the following cardiac conduction abnormalities: QTc
prolongation > 450 msec on screening electrocardiogram (ECG), congenital long-
QT-syndrome, or left bundle branch block (LBBB), previous history of QTc prolongation
with another medication that required discontinuation or any concomitant medication
that may cause QTc prolongation, or induce Torsades de Pointes

- Systolic blood pressure >= 140 mm Hg, and diastolic blood pressure >= 90 mm Hg that
is not controlled by medical therapy

- Immunocompromised patients (other than that related to the use of corticosteroids)
including patients receiving HAART (highly active anti-retroviral therapy) treatment

- Currently receiving any other investigational agent which would be considered as
treatment for cancer

- Receiving treatment with an experimental agent for non-cancer indications that has
not received regulatory approval for any indication =< 28 days prior to study entry

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Biological activity assessment defined as the change in the phosphorylation level of glycogen synthase, a direct GSK3beta target using tumor tissue and blood specimens

Outcome Description:

A paired t-test (or non-parametric equivalent) will be used to see if there is an overall decrease from baseline to any day post-baseline in these patients.

Outcome Time Frame:

From baseline to 4 hours post-treatment on day 0

Safety Issue:

No

Principal Investigator

George Kim

Investigator Role:

Principal Investigator

Investigator Affiliation:

Mayo Clinic

Authority:

United States: Food and Drug Administration

Study ID:

MC0748

NCT ID:

NCT01671202

Start Date:

September 2012

Completion Date:

Related Keywords:

  • Duct Cell Adenocarcinoma of the Pancreas
  • Stage IV Pancreatic Cancer
  • Adenocarcinoma
  • Pancreatic Neoplasms

Name

Location

Mayo ClinicRochester, Minnesota  55905