FRAGANCE: Nab-paclitaxel in Combination With Gemcitabine in Fragile Patients With Advanced Pancreatic Cancer

Sponsor

PH Research, S.L. (Other)

Overall Status

Completed

CT.gov ID

NCT02382263

Collaborator

(none)

224

Enrollment

Locations

Arms

Duration (Months)

14.9

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Advanced Pancreatic Cancer	Drug: Nab-paclitaxel 150 mg/m2 + Gemcitabine 1000 weeks 1,3/4 Drug: Nab-paclitaxel 100 mg/m2 + Gemcitabine 1000 weeks 1,2,3/4 Drug: Nab-paclitaxel 125 mg/m2 + Gemcitabine 1000 weeks 1,3/4 Drug: Nab-paclitaxel 125 mg/m2 + Gemcitabine 1000 weeks 1,2,3/4	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

224 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Apr 1, 2013

Actual Primary Completion Date :

Apr 1, 2016

Actual Study Completion Date :

Apr 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm B Nab-paclitaxel 150 mg/m2 + Gemcitabine 1000 weeks 1,3/4	Drug: Nab-paclitaxel 150 mg/m2 + Gemcitabine 1000 weeks 1,3/4 Nab-paclitaxel 150 mg/m2 + Gemcitabine 1000 days 1 & 15 in a 28 days cycle
Experimental: Arm C Nab-paclitaxel 100 mg/m2 + Gemcitabine 1000 weeks 1,2,3/4	Drug: Nab-paclitaxel 100 mg/m2 + Gemcitabine 1000 weeks 1,2,3/4 Nab-paclitaxel 100 mg/m2 + Gemcitabine 1000 days 1,8 & 15 in a 28 days cycle
Experimental: Arm D Nab-paclitaxel 125 mg/m2 + Gemcitabine 1000 weeks 1,3/4	Drug: Nab-paclitaxel 125 mg/m2 + Gemcitabine 1000 weeks 1,3/4 Nab-paclitaxel 125 mg/m2 + Gemcitabine 1000 days 1 & 15 in a 28 days cycle
Experimental: Arm E Nab-paclitaxel 125 mg/m2 + Gemcitabine 1000 weeks 1,2,3/4	Drug: Nab-paclitaxel 125 mg/m2 + Gemcitabine 1000 weeks 1,2,3/4 Nab-paclitaxel 125 mg/m2 + Gemcitabine 1000 days 1,8 & 15 in a 28 days cycle

Outcome Measures

Primary Outcome Measures

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. [Up to 2 months]
Phase I: Therapeutic index. Criteria: Early mortality all causes at 30 and 60 days, Adverse Events grade 3 and 4, treatment discontinuation due to toxicity and relative dose intensity
PHASE II: Evaluate the effectiveness of two selected schemes of gemcitabine and nab-paclitaxel, vs. gemcitabine alone. (Six months overall survival) [Up to 6 months]
Six months overall survival

Secondary Outcome Measures

Phase I: evaluate safety profile of gemcitabine and nab-paclitaxel schemes. (Number of events per patient according to NCI-CTC-AE criteria) [Up to 6 months]
Number of events per patient according to NCI-CTC-AE criteria
Phase I: evaluate objective response rate. (Response rate will be evaluated according RECIST criteria) [Up to 6 months]
Response rate will be evaluated according RECIST criteria
Phase II: progression free survival (Time from randomization to disease progression according RECIST criteria) [Up to 8 months]
Time from randomization to disease progression according RECIST criteria
Phase II: objective response rate (Response rate will be evaluated according RECIST criteria) [Up to 6 months]
Response rate will be evaluated according RECIST criteria
Phase II: to explore changes induced by treatment on tumor Marker CA19.9 [Up to 8 months]
Phase II: change in FAP and Cav-1 tumor markers as an inidicatior of treatment efficacy [Up to 6 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Complexo Hospitalario Universitario de Santiago	Santiago de Compostela	A Cosuña	Spain	15706
2	Hospital Universitario Marqués de Valdecilla	Santander	Cantabria	Spain	39008
3	Hospital Universitario Donostia	Donostia	Gipuzkoa	Spain	20014
4	Complejo Hospitalario de Navarra	Pamplona	Navarra	Spain	31008
5	Complexo Hospitalario Universitario A Coruña	A Coruña		Spain	15006
6	Hospital Universitari Vall D'Hebron	Barcelona		Spain	08035
7	Complejo Hospitalario Regional Virgen de Las Nieves	Granada		Spain	18014
8	Complejo Hospitalario Gregorio Marañón	Madrid		Spain	28007
9	Hospital Ramón Y Cajal	Madrid		Spain	28034
10	Hospital Clínico San Carlos	Madrid		Spain	28040
11	Hospital Universitario Fundación Jiménez Díaz	Madrid		Spain	28040
12	Hospital Universitario Madrid Sanchinarro	Madrid		Spain	28050
13	Complejo Hospitalario Regional de Málaga	Málaga		Spain	29010
14	Hospital Universitari I Politècnic La Fe	Valencia		Spain	46026
15	Hospital Universitario Miguel Servet	Zaragoza		Spain	50009

Sponsors and Collaborators

PH Research, S.L.

Investigators

Study Chair: Manuel Hidalgo, MD, Hospital Universitario Madrid Sanchinarro
Principal Investigator: Fernando Rivera, MD, HOSPITAL UNIVERSITARIO MARQUÉS DE VELDECILLA
Principal Investigator: Teresa Macarulla, MD, Hospital Vall d'Hebron
Principal Investigator: Carmen Guillén, MD, Hospital Universitario Ramon y Cajal
Principal Investigator: Rafael López, MD, COMPLEXO HOSPITALARIO UNIVERSITARIO DE SANTIAGO
Principal Investigator: Roberto Pazo, MD, Hospital Miguel Servet
Principal Investigator: Manuel Valladares, MD, COMPLEXO HOSPITALARIO UNIVERSITARIO A CORUÑA
Principal Investigator: Roberto P Díaz, MD, Hospital Universitario La Fe
Principal Investigator: Inmaculada Alés, MD, COMPLEJO HOSPITALARIO REGIONAL DE MÁLAGA
Principal Investigator: Joaquina Martínez, MD, COMPLEJO HOSPITALARIO REGIONAL VIRGEN DE LAS NIEVES
Principal Investigator: Adelaida La Casta, MD, Hospital Universitario Donostia
Principal Investigator: Rut Vera, MD, Complejo Hospitalario de Navarra
Principal Investigator: Andrés Muñoz, MD, COMPLEJO HOSPITALARIO GREGORIO MARAÑÓN
Principal Investigator: José I Martín, MD, HOSPITAL UNIVERSITARIO FUNDACIÓN JIMÉNEZ DIAZ
Principal Investigator: Javier Sastre, MD, Hospital San Carlos, Madrid