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

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

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.

Study Overview

• Status: Completed
• Conditions: Advanced Pancreatic Cancer
• Intervention / Treatment: 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

• Study Type: Interventional
• Enrollment (Actual): 224
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Spain
  • A Coruña, Spain, 15006
    • Complexo Hospitalario Universitario A Coruña
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebrón
  • Granada, Spain, 18014
    • Complejo Hospitalario Regional Virgen de las Nieves
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28040
    • Hospital Universitario Fundacion Jimenez Diaz
  • Madrid, Spain, 28034
    • Hospital Ramon y Cajal
  • Madrid, Spain, 28050
    • Hospital Universitario Madrid Sanchinarro
  • Madrid, Spain, 28007
    • Complejo Hospitalario Gregorio Marañón
  • Málaga, Spain, 29010
    • Complejo Hospitalario Regional de Málaga
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet
  • A Cosuña
    • Santiago de Compostela, A Cosuña, Spain, 15706
      • Complexo Hospitalario Universitario De Santiago
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Universitario Marqués de Valdecilla
  • Gipuzkoa
    • Donostia, Gipuzkoa, Spain, 20014
      • Hospital Universitario Donostia
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Complejo Hospitalario de Navarra

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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

Collaborators and Investigators

• Sponsor: PH Research, S.L.
• Investigators: Principal Investigator: Teresa Macarulla, MD, Hospital Vall d'Hebron; Study Chair: Manuel Hidalgo, MD, Hospital Universitario Madrid Sanchinarro; Principal Investigator: Fernando Rivera, MD, HOSPITAL UNIVERSITARIO MARQUÉS DE VELDECILLA; 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 Fundacion Jimenez Diaz; Principal Investigator: Javier Sastre, MD, Hospital San Carlos, Madrid

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Actual): April 1, 2016
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: February 24, 2015
• First Submitted That Met QC Criteria: March 2, 2015
• First Posted (Estimate): March 6, 2015

Study Record Updates

• Last Update Posted (Estimate): July 6, 2016
• Last Update Submitted That Met QC Criteria: July 5, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: Nab-paclitaxel; Advanced pancreatic cancer; Fragile
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Gemcitabine; Paclitaxel; Albumin-Bound Paclitaxel
• Other Study ID Numbers: PHR-2012-01