Clinical trial NCT02382263: Nab-paclitaxel in Combination With Gemcitabine in Fragile Patients With Advanced Pancreatic Cancer
Official title: Phase I/II Study to Assess the Efficacy and Safety of Nab-paclitaxel in Combination With Gemcitabine for the Treatment of Fragile Patients With Advanced or Metastatic Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Advanced Pancreatic Cancer
Keywords: Advanced pancreatic cancer
Fragile
Nab-paclitaxel
Lead sponsor: PH Research, S.L.
Sponsor class: OTHER
First posted: 2015-03-06
Enrollment: 224
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In the list of cancer mortality by type of cancer pancreatic cancer ranks 4th in USA and the 6th in Europe. The estimated figures for 2010 in the USA were 42,000 new cases and 36,000 deaths from pancreatic cancer. The survival rate at 5 years after diagnosis is 4.6% in the USA. In Europe the figures are similar, with survival at 1, 3 and 5 years of 16%, 6% and 4%, respectively. Most patients are diagnosed in advanced stages that are no longer operable, so that treatment goals are often the prolongation of survival and palliation of symptoms.

The aim of the study is to explore whether the new combination nab-paclitaxel plus gemcitabine is a therapeutic advance for this fragile population for which it is assumed that some modifications in dose and schedule of administration may be necessary in patients with good performance status. It is ultimately to find out the clinical benefit of this combination, but first making sure that dose and schedule of the combination are tolerable for these fragile patients.

For this, the investigators have chosen a design that includes two stages: the first step aimed at choosing the safest treatment regimen for these patients among a group of treatment regimens used in other clinical trials. The second step will evaluate the effectiveness of the two regimens with the better results in the previous step.


Eligibility criteria: Inclusion Criteria:

* Patients who are 18 years or older;
* Patients with histological or, if not possible, cytologic confirmed adenocarcinoma of the pancreas.
* Patients with metastatic pancreatic cancer;
* Patient with an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) = 2
* Adequate hematopoietic, hepatic and renal function:
* Neutrophil count \>= 1.5 x 10\*9/L;
* Platelet count \>= 100 x 10\*9/L;
* Bilirubin \<= 1.5 x ULN;
* AST and/or ALT \<= 2.5 x ULN;
* Serum creatinine \<= 1.5 x ULN.
* Investigators must ensure that patients enrolled in the study will be available for all study procedures, including tumor biopsy, chemotherapy treatment, and follow up.
* Investigators must ensure that patients have the ability to understand the requirements of the study and provide signed informed consent.
* Women of childbearing potential and men who wish to participate in the study must agree to use adequate contraception since the signing of informed consent until at least 3 months after stopping the study medication;
* Signed Informed Consent.

Exclusion Criteria:

* Active or uncontrolled infections or serious illnesses or medical conditions that could interfere with patient eligibility for treatment;
* History of any psychiatric condition that might impair patient?s ability to understand or to comply with the requirements of the study or to provide informed consent;
* Concurrent anticancer therapy;
* Pregnant or breast-feeding women (documented methods of birth control are required in those with reproductive potential);
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to study drugs;
* History of life threatening reaction to gemcitabine or abraxane;
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) \<=1.
* Previous treatment with chemotherapy or chemoradiotherapy for advanced pancreatic cancer.

Primary outcomes:
measure: PHASE I: To select the schemes with the best therapeutic indexes of the combination of gemcitabine and nab-paclitaxel in fragile patients with advanced pancreatic cancer.
timeFrame: Up to 2 months
measure: PHASE II: Evaluate the effectiveness of two selected schemes of gemcitabine and nab-paclitaxel, vs. gemcitabine alone. (Six months overall survival)
timeFrame: Up to 6 months
Secondary outcomes:
measure: Phase I: evaluate safety profile of gemcitabine and nab-paclitaxel schemes. (Number of events per patient according to NCI-CTC-AE criteria)
timeFrame: Up to 6 months
measure: Phase I: evaluate objective response rate. (Response rate will be evaluated according RECIST criteria)
timeFrame: Up to 6 months
measure: Phase II: progression free survival (Time from randomization to disease progression according RECIST criteria)
timeFrame: Up to 8 months
measure: Phase II: objective response rate (Response rate will be evaluated according RECIST criteria)
timeFrame: Up to 6 months
measure: Phase II: to explore changes induced by treatment on tumor Marker CA19.9
timeFrame: Up to 8 months
measure: Phase II: change in FAP and Cav-1 tumor markers as an inidicatior of treatment efficacy
timeFrame: Up to 6 months
Other outcomes:
Locations:
city: Santiago de Compostela
country: Spain
facility: Complexo Hospitalario Universitario de Santiago
state: A Cosuña
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla
state: Cantabria
city: Donostia
country: Spain
facility: Hospital Universitario Donostia
state: Gipuzkoa
city: Pamplona
country: Spain
facility: Complejo Hospitalario de Navarra
state: Navarra
city: A Coruña
country: Spain
facility: Complexo Hospitalario Universitario A Coruña
city: Barcelona
country: Spain
facility: Hospital Universitari Vall D'Hebron
city: Granada
country: Spain
facility: Complejo Hospitalario Regional Virgen de Las Nieves
city: Madrid
country: Spain
facility: Complejo Hospitalario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Ramón Y Cajal
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital Universitario Madrid Sanchinarro
city: Málaga
country: Spain
facility: Complejo Hospitalario Regional de Málaga
city: Valencia
country: Spain
facility: Hospital Universitari I Politècnic La Fe
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
Study officials:
affiliation: Hospital Universitario Madrid Sanchinarro
name: Manuel Hidalgo, MD
role: STUDY_CHAIR
affiliation: HOSPITAL UNIVERSITARIO MARQUÉS DE VELDECILLA
name: Fernando Rivera, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Vall d'Hebron
name: Teresa Macarulla, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario Ramon y Cajal
name: Carmen Guillén, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: COMPLEXO HOSPITALARIO UNIVERSITARIO DE SANTIAGO
name: Rafael López, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Miguel Servet
name: Roberto Pazo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: COMPLEXO HOSPITALARIO UNIVERSITARIO A CORUÑA
name: Manuel Valladares, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario La Fe
name: Roberto P Díaz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: COMPLEJO HOSPITALARIO REGIONAL DE MÁLAGA
name: Inmaculada Alés, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: COMPLEJO HOSPITALARIO REGIONAL VIRGEN DE LAS NIEVES
name: Joaquina Martínez, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Donostia
name: Adelaida La Casta, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Complejo Hospitalario de Navarra
name: Rut Vera, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: COMPLEJO HOSPITALARIO GREGORIO MARAÑÓN
name: Andrés Muñoz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: HOSPITAL UNIVERSITARIO FUNDACIÓN JIMÉNEZ DIAZ
name: José I Martín, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital San Carlos, Madrid
name: Javier Sastre, MD
role: PRINCIPAL_INVESTIGATOR
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