Afatinib and Gemcitabine/Nab-paclitaxel in Metastatic Pancreatic Cancer

NCT02975141 | Unknown Phase 1 DMC

• 1 other identifier: 2015-004065-86
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This study sets out to determine the maximum tolerated dose (MTD) of afatinib in combination with gemcitabine/nab-paclitaxel in patients with metastatic pancreatic ductal adenocarcinoma. The identified MTD will serve as recommended phase II dose (RP2D).

Conditions

Metastatic Pancreatic Cancer

Keywords

Palliative Chemotherapy; Afatinib; Gemcitabine; nab-paclitaxel; pancreatic cancer

Outcome Measures

Primary Outcomes (1)

• MTD of afatinib in combination with gemcitabine/nab-paclitaxel

  Completion of the first cycle of chemotherapy

  28 days after the first dose of chemotherapy

Secondary Outcomes (4)

• RECIST measurements of target lesions (in cm/inches)

  18 months

• Progression free survival (in months)

  18 months

• Overall survival (in months)

  18 months

• Incidence of Treatment-Emergent Adverse Events

  18 months

Study Arms (4)

Afatinib 40Mg Tab, Gemzar, Abraxane +1

EXPERIMENTAL

Dose Level +1 Afatinib 40 mg Nab-paclitaxel 125 mg/m2 BSA Gemcitabine 1000 mg/m2 BSA

Drug: Afatinib 40Mg Tab; Drug: Gemzar; Drug: Abraxane

Afatinib 30Mg Tab, Gemzar, Abraxane 0

EXPERIMENTAL

Dose Level 0 Afatinib 30 mg Nab-paclitaxel 125 mg/m2 BSA Gemcitabine 1000 mg/m2 BSA

Drug: Afatinib 30Mg Tab; Drug: Gemzar; Drug: Abraxane

Afatinib 30Mg Tab, Gemzar, Abraxane -1

EXPERIMENTAL

Dose Level -1 Afatinib 30 mg Nab-paclitaxel 100 mg/m2 BSA Gemcitabine 800 mg/m2 BSA

Drug: Afatinib 30Mg Tab; Drug: Gemzar; Drug: Abraxane

Afatinib 30Mg Tab, Gemzar, Abraxane -2

EXPERIMENTAL

Dose Level -2 Afatinib 30 mg Nab-paclitaxel 75 mg/m2 BSA Gemcitabine 600 mg/m2 BSA

Drug: Afatinib 30Mg Tab; Drug: Gemzar; Drug: Abraxane

Interventions

Afatinib 30Mg Tab DRUG

Study Drug

Also known as: Giotrif

Afatinib 30Mg Tab, Gemzar, Abraxane -1; Afatinib 30Mg Tab, Gemzar, Abraxane -2; Afatinib 30Mg Tab, Gemzar, Abraxane 0

Afatinib 40Mg Tab DRUG

Study Drug

Also known as: Giotrif

Afatinib 40Mg Tab, Gemzar, Abraxane +1

Gemzar DRUG

Chemotherapy Backbone

Also known as: Gemcitabine

Afatinib 30Mg Tab, Gemzar, Abraxane -1; Afatinib 30Mg Tab, Gemzar, Abraxane -2; Afatinib 30Mg Tab, Gemzar, Abraxane 0; Afatinib 40Mg Tab, Gemzar, Abraxane +1

Abraxane DRUG

Chemotherapy Backbone

Also known as: nab-Paclitaxel

Afatinib 30Mg Tab, Gemzar, Abraxane -1; Afatinib 30Mg Tab, Gemzar, Abraxane -2; Afatinib 30Mg Tab, Gemzar, Abraxane 0; Afatinib 40Mg Tab, Gemzar, Abraxane +1

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients ≥ 18 years of age and ≤ 75 years
• Histologically (not cytologically) confirmed diagnosis of metastatic pancreatic ductal adenocarcinoma (PDAC) \[Stage IV according to UICC TNM edition 7 of 2009: each T, each N, M1\]
• No option for surgical resection or radiation in curative intent
• At least one unidimensionally measurable tumor lesion (according to RECIST 1.1)
• ECOG performance status 0 - 1
• Life expectancy at least 3 months
• Adequate hepatic, renal and bone marrow function, defined as:
• Absolute neutrophil count (ANC) ≥ 1.5x109/L
• Haemoglobin ≥ 9 g/dL 9
• Thrombocytes ≥100x10/L
• Total bilirubin ≤ 1.5xULN.
• Patients with a biliary stent may be included provided that bilirubin level after stent insertion decreased to ≤ 1.5 x ULN and there is no cholangitis.
• AST/GOT and/or ALT/GPT ≤ 2.5 x ULN or in case of liver metastasis ≤ 5 x ULN)
• Serum creatinine within normal limits or creatinine clearance ≥60 mL/min/1.73 m2 as calculated by CKD- EPI formula for patients with serum creatinine levels above or below the institutional normal value.
• Acceptable coagulation studies defined as prothrombin time (or INR) and PTT ≤ 1.5 x ULN

You may not qualify if:

• Locally advanced PDAC without metastasis
• Evidence of ascites
• Known metastatic disease to the brain. Brain imaging is required in symptomatic patients to rule out brain metastases, but is not required in asymptomatic patients.
• Previous palliative chemotherapy or other palliative systemic tumor therapy for metastatic disease of PDAC
• Previous gemcitabine treatment with exception of gemcitabine treatment applied as monotherapy in the adjuvant setting (after potential curative R0 or R1 resection) and if the adjuvant single-agent gemcitabine chemotherapy was terminated at least 6 months before study entry
• Previous radiotherapy of PDAC
• Previous ErbB family directed therapy for PDAC (e. g. erlotinib, cetuximab, trastuzumab, lapatinib)
• Any major surgery within the last 4 weeks before study entry
• Clinical significant decrease in performance status within 2 weeks of intended first application of study medication (by medical history)
• Severe tumor-related cachexia and/or known weight loss \>15% within one month before study enrollment
• Pre-existing polyneuropathy ≥ grade 2 according to CTCAE version 4.03
• LDH \>2.5xULN
• Significant (≥ 20%) decrease in serum albumin levels within 2 weeks of intended first application of study medication (by medical history)
• Gastrointestinal disorders that might interfere with the absorption of the study drug and gastrointestinal disorders with diarrhoea as a major symptom (e.g. Crohn's disease, malabsorption), and chronic diarrhoea of any aetiology CTCAE version 4.03 grade ≥ 2
• Medical history of interstitial lung disease (ILD) or pulmonary fibrosis or severe COPD

Sponsors & Collaborators

• PD Dr. med. Volker Heinemann: lead
• Technical University of Munich: collaborator
• University of Cologne: collaborator

Study Sites (1)

Ludwig-Maximilians - University of Munich

Munich, 81377, Germany

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Afatinib; Gemcitabine; Albumin-Bound Paclitaxel; 130-nm albumin-bound paclitaxel

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Volker Heinemann, Professor

  University of Munich - Klinikum Großhadern

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: September 21, 2016
• First Posted: November 29, 2016
• Study Start: September 1, 2016
• Primary Completion: December 1, 2018
• Study Completion: June 1, 2019
• Last Updated: August 13, 2018

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)