Adjuvant Effect of Chloroquine on Gemcitabine

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety by defining the maximum tolerated dose (MTD) of Choloroquine when combined with Gemcitabine, and to evaluate preliminary efficacy of combined systemic Gemcitabine and Chloroquine. In addition, the influence of the treatment on the anti-cancer immunity and the value of GOLPH2 as serum marker for pancreatic cancer will be assessed within a translational objective. Trial with medicinal product

Official Title
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Gemcitabine Combined With Chloroquine in Patients With Metastatic or Unresectable Pancreatic Cancer. A Dose Finding Single Center Phase I Study

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: Chloroquine
* Drug: Gemcitabine


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Histologically or cytologically confirmed non-resectable locally advanced or metastatic adenocarcinoma of the pancreas. Assessment is done within 21 days before enrolment. Age = 18 years Adequate liver function or kidney function tests, including any of the following: Bilirubin < 2 x ULN, Alanin-Aminotransferase (ALT) < 5 x ULN, Alcaline phosphatase < 5 x ULN, Estimated creatinine clearance > 40 ml/min (using the Cockroft formula) Adequate haematological values: Haemoglobin > 80 g/L, Leukocytes >3.00 g/L, Neutrophils > 1.00 g/L, Platelets > 100 g/L Written informed consent Biliary decompression is mandatory before inclusion into the study in case of bilirubin levels > 50 µmol/L. Women who are not breastfeeding and are using effective contraception if sexually active, who are not pregnant and agree not to become pregnant during the 12 months thereafter. A negative pregnancy test before inclusion into the trial is required for women of childbearing potential, defined as having not reached the menopause, last menstrual period occurred less than 12 months ago, no surgical sterilization performed, and fallopian tubes and/or uterus have been not surgically removed. Men who agree not to father a child during participation in the trial or during the 12 months thereafter. Patient compliance and geographic proximity allow proper staging and follow-up. Patient not eligible for FOLFIRINOX treatment. WHO PS 0-2 Exclusion criteria: Life expectancy < 3 months Severe medical or psychiatric co-morbidity prohibiting the planned treatment or the giving of informed consent Any prior chemotherapy for pancreatic cancer, including adjuvant chemotherapy. Any prior radiotherapy or combined radio-chemotherapy for pancreatic cancer if completed less than 12 months prior to study inclusion. Known hypersensitivity to trial drugs or hypersensitivity to any other component of the trial drugs. Known glucose-6-phosphate dehydrogenase deficiency. Concurrent use of other experimental drugs, treatment within a clinical trial within 30 days prior to trial entry. Active heart disease defined as congestive heart failure > NYHA class 2 Past or current history (within the last 2 years prior to treatment start) of other malignancies except basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix Inability or unwillingness to comply with the study protocol No understanding of the german language

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chloroquin in addition to Gemcitabine<br>Gemcitabine 1000 mg/m2 i.v. at days 1, 8, 15 of every 28-day cycle. Chloroquine 100 mg, 200 mg or 300 mg (according to dose level) p.o. at days 2, 9, 16 of every 28-day cycle. | Drug: Chloroquine<br>* Addition of Chloroquine to Gemcitabine<br>* Other names: Nivaquin;Drug: Gemcitabine<br> <br> * Other names: Gemzar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (MTD) of orally administered Chloroquine with concomitant intravenous Gemcitabine. |  | 8 weeks |