Randomized Phase II Trial of Pre-Operative Gemcitabine an... | NCT01978184

NCT01978184

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
gemcitabine and abraxane	Experimental	Gemcitabine and Abraxane will be administered on an outpatient basis on Days 3, 10, 17, 31, 38, and 45 as an intravenous infusion. The dose on Day 3 will be 1000 mg/m of gemcitabine followed by a 125 mg/m2 of abraxane and the infusion will take 1 hour. The second dose and infusion time may be decreased. Prior to each gemcitabine infusion, subjects will be pre-medicated with an FDA-approved anti-emetic (anti-nausea medication) in an effort to prevent nausea, at the discretion of the study physician.	Drug: gemcitabine Drug: abraxane
gemcitabine, abraxane and hydroxychloroquine	Experimental	Gemcitabine and Abraxane will be administered on an outpatient basis on Days 3, 10, 17, 31, 38, and 45 as an intravenous infusion. The dose on Day 3 will be 1000 mg/m of gemcitabine followed by a 125 mg/m2 of abraxane and the infusion will take 1 hour. The second dose and infusion time may be decreased. Prior to each gemcitabine infusion, subjects will be pre-medicated with an FDA-approved anti-emetic (anti-nausea medication) in an effort to prevent nausea, at the discretion of the study physician. Hydroxychloroquine is an oral drug (capsule) that subjects will take once or twice a day at home. The dose of hydroxychlorquien will be 1200mg. This is an experimental drug. Subjects will take their first dose of hydroxychloroquine on Day 1 (48 hours before the first infusion of gemcitabine/abraxane), and will continue to take it every day until the day before surgery.	Drug: gemcitabine Drug: abraxane Drug: hydroxychloroquine

Name	Type	Description	Arm Group Labels	Other Names
gemcitabine	Drug		gemcitabine and abraxane gemcitabine, abraxane and hydroxychloroquine	Gemzar

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Evans Grade Histopathologic Response	The number of patients who exhibited an Evans grade Histologic response (I, IIA, IIB, or III) to pre-operative gemcitabine / nab-paclitaxel. Histological response validated scoring system by Evans is as follows: Grade I: 1-9% tumor destruction, Grade II: 10 - 90%, Grade III: >90% tumor destruction (Grade IIA = 10-50% of tumor cells destroyed; Grade IIB = 50-90% of tumor cells destroyed), Grade IV: Absence of viable tumor cells.	Up to 4 years
Age at Diagnosis	The mean age of patients at the time of diagnosis of disease (as a variable in the proportional odds logistic regression, secondary analysis of Evans Grade).	Baseline - At the time of diagnosis, prior to treatment
CT Tumor Size	Tumor size as measured via computerized tomography (CT) scan (as a variable in the proportional odds logistic regression, secondary analysis of Evans Grade).	Baseline - At the time of diagnosis, prior to treatment
Cancer Diagnosis Stage	The number of participants in cancer diagnosis stage groups. Stage 0: cancer hasn't spread to nearby tissues/located in the same of origin.Stage I: cancers hasn't grown deeply into nearby tissues or spread to lymph nodes or other parts of the body. Stage II and III: cancers have grown more deeply into nearby tissues (may have metastasized to lymph nodes but not other parts of the body). Stage IV: most advanced stage (metastatic cancer) ; cancer has spread to other parts of the body. Stages subdivided further into the categories "A" (less agressive disease) and "B" (more advanced cancer). Example: stage IIA is less aggressive than stage IIB, but stage IIIA is more aggressive than stage IIB. (Stage variable used in the proportional odds logistic regression, secondary analysis of Evans Grade).	Baseline - At the time of diagnosis, prior to treatment
Type of Surgical Procedure (Operation)

Secondary Outcomes

Measure	Description	Time Frame
Carbohydrate Antigen 19-9 (CA19-9) Response	Levels of Carbohydrate antigen 19-9 (CA19-9) response to pre-operative gemcitabine/ nab-paclitaxel measured in the serum (original scale)	Prior to treatment (average 73.3 +/- 9.9 days prior to surgery)
Carbohydrate Antigen 19-9 (CA19-9) Response

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Subjects with biopsy-proven potentially resectable or borderline adenocarcinoma of the pancreas as determined by National Comprehensive Cancer Network (NCCN) criteria
Karnofsky performance status of 70-100%
No active second malignancy except for basal cell carcinoma of the skin
Patient has adequate biological parameters as demonstrated by the following blood counts at screening
Absolute neutrophil count (ANC) ≥1.5 × 109/L;
Platelet count ≥100,000/mm3 (100 × 109/L);
Hemoglobin (Hgb) ≥9 g/dL.
Patient has the following blood chemistry levels at Baseline
aspartate aminotransferase (AST) (SGOT), Alanine transaminase (SGPT) ≤2.5 × upper limit of normal range (ULN)
Total bilirubin ≤ULN
Serum Creatinine ≤ 1.5mg/dl OR calculated creatinine clearance ≥ 50 for those patients with creatinine greater than 1.5
Prothrombin time (PT)within normal limits (WNL). If patient is on warfarin for prophylactic clot presentation for indwelling catheter, Partial PT/PTT may be +/- 15 %
thromboplastin time (PTT) WNL. If patient on warfarin for prophylactic clot presentation for indwelling catheter, PT/PTT may be +/- 15 %
Age >18 years.
Patient must be able to swallow enteral medications with no requirement for a feeding tube. Patient's must not have intractable nausea or vomiting which prohibits the patient from oral medications
Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

Subjects deemed surgically unresectable or subjects unwilling to undergo surgical resection.
Subjects who have received chemotherapy within 12 months prior to randomization.
Prior use of radiotherapy or investigational agents for pancreatic cancer.
Any evidence of metastasis to distant organs (liver, lung, peritoneum).
Symptomatic evidence of gastric outlet obstruction
Inability to adhere to study and/or follow-up procedures
History of allergic reactions or hypersensitivity to the study drugs (hydroxychloroquine, gemcitabine, abraxane).
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. All females of childbearing potential must have a blood test or urine study within two weeks prior to randomization to rule out pregnancy.
Patients with porphyria are ineligible.
Patients with psoriasis are ineligible unless the disease is well controlled and they are under the care of a specialist who agrees to monitor the patient for exacerbations.
Patients requiring the use of enzyme-inducing anti-epileptic medication that includes: phenytoin, carbamazepine, phenobarbital, primidone or oxcarbazepine are excluded.
Patients with previously documented macular degeneration or diabetic retinopathy are excluded.
Baseline electrocardiogram (EKG) with corrected QT interval (QTc) >470 msec (including subjects on medication). Subjects with ventricular pacemaker for whom QT interval is not measurable will be eligible on a case-by-case basis.
Patient with a history of interstitial lung disease, history of slowly progressive dyspnea, sarcoidosis, silicosis, idiopathic pulmonary fibrosis or pulmonary hypersensitivity pneumonitis
Patient with known active infection with HIV, Hepatitis B or Hepatitis C
Patients requiring use of warfarin for therapeutic purposes.

Name	Affiliation	Role
Herbert Zeh, MD	University of Pittsburgh CancerCenters	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Hillman Cancer Center		Pittsburgh	Pennsylvania	15232	United States

PubMed Identifier	Type	Citation	Retractions
31428515	Derived	Miller-Ocuin JL, Liang X, Boone BA, Doerfler WR, Singhi AD, Tang D, Kang R, Lotze MT, Zeh HJ 3rd. DNA released from neutrophil extracellular traps (NETs) activates pancreatic stellate cells and enhances pancreatic tumor growth. Oncoimmunology. 2019 Jun 11;8(9):e1605822. doi: 10.1080/2162402X.2019.1605822. eCollection 2019.
29929491

Arm/Group Information

ID	Title	Description
FG000	Gemcitabine + Abraxane	Gemcitabine and Abraxane administered as an intravenous infusion on Study Days 3, 10, 17, 31, 38, and 45. Day 3 dosing: 1 hour infusion - 1000 mg/m^2 of gemcitabine followed by a 125 mg/m^2 of abraxane. Prior to each gemcitabine infusion, subjects were pre-medicated with an FDA-approved anti-emetic (anti-nausea medication) in an effort to prevent nausea, at the discretion of the study physician.
FG001	Gemcitabine + Abraxane and Hydroxychloroquine	Gemcitabine and Abraxane administered as an intravenous infusion on Study Days 3, 10, 17, 31, 38, and 45. Day 3 dosing: 1 hour infusion - 1000 mg/m^2 of gemcitabine followed by a 125 mg/m^2 of abraxane. Prior to each gemcitabine infusion, subjects were pre-medicated with an FDA-approved anti-emetic (anti-nausea medication) in an effort to prevent nausea, at the discretion of the study physician. Hydroxychloroquine oral capsules taken once or twice a daily at a dose of 1200mg. The first dose of hydroxychloroquine taken on Day 1 (48 hours before the first infusion of gemcitabine/abraxane), and continued daily until one day before surgery.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Gemcitabine + Abraxane	Gemcitabine and Abraxane administered as an intravenous infusion on Study Days 3, 10, 17, 31, 38, and 45. Day 3 dosing: 1 hour infusion - 1000 mg/m^2 of gemcitabine followed by a 125 mg/m^2 of abraxane. Prior to each gemcitabine infusion, subjects were pre-medicated with an FDA-approved anti-emetic (anti-nausea medication) in an effort to prevent nausea, at the discretion of the study physician.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Evans Grade Histopathologic Response

The number of patients who exhibited an Evans grade Histologic response (I, IIA, IIB, or III) to pre-operative gemcitabine / nab-paclitaxel. Histological response validated scoring system by Evans is as follows: Grade I: 1-9% tumor destruction, Grade II: 10 - 90%, Grade III: >90% tumor destruction (Grade IIA = 10-50% of tumor cells destroyed; Grade IIB = 50-90% of tumor cells destroyed), Grade IV: Absence of viable tumor cells.

Patients who went to surgery and were evaluable for Evans Grade Histopathologic Response.

Posted

Number

number of participants

Up to 4 years

ID	Title	Description
OG000	Gemcitabine + Abraxane	Gemcitabine and Abraxane administered as an intravenous infusion on Study Days 3, 10, 17, 31, 38, and 45. Day 3 dosing: 1 hour infusion - 1000 mg/m^2 of gemcitabine followed by a 125 mg/m^2 of abraxane. Prior to each gemcitabine infusion, subjects were pre-medicated with an FDA-approved anti-emetic (anti-nausea medication) in an effort to prevent nausea, at the discretion of the study physician.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Gemcitabine + Abraxane	Gemcitabine and Abraxane administered as an intravenous infusion on Study Days 3, 10, 17, 31, 38, and 45. Day 3 dosing: 1 hour infusion - 1000 mg/m^2 of gemcitabine followed by a 125 mg/m^2 of abraxane. Prior to each gemcitabine infusion, subjects were pre-medicated with an FDA-approved anti-emetic (anti-nausea medication) in an effort to prevent nausea, at the discretion of the study physician.

ID	Term
D004067	Digestive System Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D004701	Endocrine Gland Neoplasms

ID	Term
D000093542	Gemcitabine
D000068196	Albumin-Bound Paclitaxel
D006886	Hydroxychloroquine

ID	Term
D006571	Heterocyclic Compounds
D003841	Deoxycytidine
D003562	Cytidine
D011741	Pyrimidine Nucleosides