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

Advanced Pancreatic Cancer Clinical Trial

— FRAGANCE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02382263
• Other study ID #: PHR-2012-01
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: February 24, 2015
• Last updated: July 5, 2016
• Start date: April 2013
• Est. completion date: April 2016

Study information

• Verified date: July 2016
• Source: PH Research, S.L.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Agencia Española de Medicamentos y Productos Sanitarios
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 224
• Est. completion date: April 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Advanced Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

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
• 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
• 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
• 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

Locations

Country	Name	City	State
Spain	Complexo Hospitalario Universitario A Coruña	A Coruña
Spain	Hospital Universitari Vall D'Hebron	Barcelona
Spain	Hospital Universitario Donostia	Donostia	Gipuzkoa
Spain	Complejo Hospitalario Regional Virgen de Las Nieves	Granada
Spain	Complejo Hospitalario Gregorio Marañón	Madrid
Spain	Hospital Clínico San Carlos	Madrid
Spain	Hospital Ramón Y Cajal	Madrid
Spain	Hospital Universitario Fundación Jiménez Díaz	Madrid
Spain	Hospital Universitario Madrid Sanchinarro	Madrid
Spain	Complejo Hospitalario Regional de Málaga	Málaga
Spain	Complejo Hospitalario de Navarra	Pamplona	Navarra
Spain	Hospital Universitario Marqués de Valdecilla	Santander	Cantabria
Spain	Complexo Hospitalario Universitario de Santiago	Santiago de Compostela	A Cosuña
Spain	Hospital Universitari I Politècnic La Fe	Valencia
Spain	Hospital Universitario Miguel Servet	Zaragoza

Sponsors (1)

Lead Sponsor	Collaborator
PH Research, S.L.

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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	Up to 2 months	Yes
Primary	PHASE II: Evaluate the effectiveness of two selected schemes of gemcitabine and nab-paclitaxel, vs. gemcitabine alone. (Six months overall survival)	Six months overall survival	Up to 6 months	No
Secondary	Phase I: evaluate safety profile of gemcitabine and nab-paclitaxel schemes. (Number of events per patient according to NCI-CTC-AE criteria)	Number of events per patient according to NCI-CTC-AE criteria	Up to 6 months	Yes
Secondary	Phase I: evaluate objective response rate. (Response rate will be evaluated according RECIST criteria)	Response rate will be evaluated according RECIST criteria	Up to 6 months	No
Secondary	Phase II: progression free survival (Time from randomization to disease progression according RECIST criteria)	Time from randomization to disease progression according RECIST criteria	Up to 8 months	No
Secondary	Phase II: objective response rate (Response rate will be evaluated according RECIST criteria)	Response rate will be evaluated according RECIST criteria	Up to 6 months	No
Secondary	Phase II: to explore changes induced by treatment on tumor Marker CA19.9		Up to 8 months	No
Secondary	Phase II: change in FAP and Cav-1 tumor markers as an inidicatior of treatment efficacy		Up to 6 months	No