Gemcitabine Plus Erlotinib in RASH-positive Patients With Metastatic Pancreatic Cancer (ML22774)

July 16, 2017 updated by: PD Dr. med. Volker Heinemann, Ludwig-Maximilians - University of Munich

Phase II Study to Evaluatate the Efficacy of Gemcitabine Plus Erlotinib for RASH-positive Patients With Metastatic Pancreatic Cancer and Friendly Risk Circumstances

In the current study it is examined whether patients with good risk factors (age <75 years, total serum bilirubin < 1,5xULN, no history of cardiovascular diseases) treated with gemcitabine and erlotinib who developed skin rash of any grade during the first 4 weeks of treatment have a comparable outcome as patients who receive FOLFIRINOX.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The study by Burris et al. 1997 revealed a superiority of gemcitabine vs. 5-FU in terms of improvement of general condition, pain symptoms and overall survival in patients with locally advanced or metastatic pancreatic cancer. Subsequently, gemcitabine was established as a standard treatment for locally advanced and metastatic pancreatic cancer.

In a series of studies gemcitabine was combined with other chemotherapeutic agents or targeted therapies. For the first time, the PA.03 study showed a significant improvement of overall survival. Patients who were treated with gemcitabine plus erlotinib had a survival of 6.24 months, compared with 5.91 months for those treated with gemcitabine plus placebo (HR 0.82, 95% CI 0.69-0.99, p=0.038). The one-year-survival rate was 23% for gemcitabine plus erlotinib vs. 17% for gemcitabine plus placebo.

In a subgroup analysis of the PA.03 study, patients developing a skin rash NCI CTC ≥ grade 2 had an advanced survival (one-year-survival rate 43%) vs. those with grade 1 or 0 (one-year-survival rate 16% and 9%, respectively). Later studies confirmed the correlation between skin rash and survival.

While patients developing a skin rash of any grade seem to profit most from treatment with erlotinib, the prognosis for those without rash is rather dismal. In this population, survival varied between 3.3 and 4.8 months in clinical trials (Verslype et al. 2009, Boeck et al. 2010, Manzano et al. 2010). In this patients, a modification of the treatment strategy should be considered. Which kind of treatment might lead to optimal results in these patients is not yet clear.

In patients with excellent general condition complying with further prerequisits (age <75 years, total serum bilirubin < 1,5xULN, no history of cardiovascular diseases) the French Prodige study-group could show a statistical superiority for the gemcitabine-free FOLFIRINOX-scheme in terms of overall survival, progression free survival and response rate compared to gemcitabine alone. However, this superiority was gained at the expense of treatment tolerability. During treatment with FOLFIRINOX a grade 3-4 neutropenia was observed in 5.4% and a grade 3-4 diarrhea in 12.7% of patients (Conroy et al. 2011). For patients who comply with the above-named criteria FOLFIRINOX is considered an established standard of care.

If a comparable efficacy of gemcitabine plus erlotinib with the published FOLFIRINOX data can be seen in the selected population, this would favour, due to the worse tolerability of FOLFIRINOX, the use of gemcitabine plus erlotinib.

In summary, the following selections are conducted during the study:

  1. Selection due to the inclusion criteria for treatment with FOLFIRINOX provided by Conroy et al.
  2. Selection due to the development of a skin rash within four weeks of treatment
  3. No signs of clinical tumour progression within the run-in phase within the first four weeks of treatment

Patients who do not develope a skin rash of any grade should be treated with FOLFIRINOX. The efficacy of FOLFIRINOX in rash-negative patients has not yet been investigated.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
150

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Munich, Germany, 81377
        • University of Munich

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologically (not cytologically) confirmed metastatic pancreatic adenocarcinoma (stage IV according to UICC, each T, each N, M1 according to TNM)
  • At least one measurable index lesion (CT or MRI) according to RECIST criteria (V 1.1)
  • ECOG PS 0 and 1
  • Age 18-75 years
  • Serum bilirubin ≤1,5x ULN (a placed biliary tract stent without concurrent cholangitis is not considered a contraindication)
  • Availability of tumour samples (no cytologic samples)
  • Written informed consent by the patient for collecting blood- and tumour-samples for translational research according to study protocol
  • Live expectancy of at least three months
  • Written informed consent
  • Negative pregnancy test in women with childbearing potential (to be performed within 7 days prior to treatment start)
  • Adequate kidney-, liver- and bone-marrow function: neutrophils >= 1500/µl, platelets >= 100.000/µ, and hemoglobin >= 8g/dl, liver transaminases<= 2,5x ULN, in case of liver metastases <= 5x ULN, serum creatinine <= 1,25x ULN, creatinine clearance ≥ 30 ml/min
  • Legal capacity of the patient
  • Option for constant long-term follow-up

Exclusion Criteria:

  • Resectable pancreatic carcinoma
  • Locally advanced pancreatic cancer (non-resectable tumour without distant metastasis)
  • Previous palliative chemotherapy for metastatic or locally advanced, non-resectable pancreatic cancer
  • Previous palliative radiation or chemoradiation for locally advanced, non-resectable pancreatic cancer
  • Radiation therapy within four weeks prior to study enrolment or radiation of indicator lesions
  • Adjuvant Chemotherapy or Radiochemotherapy for pancreatic cancer ≤ 6 months prior to study ernrolment
  • All previously occurred metastatic cancers or cured neoplasias diagnosed within the last 5 years before study enrolment
  • Major surgery within 2 weeks before study start
  • Chronic diarrhea
  • Known glucuronidation-deficiency (Gilbert´s syndrome)
  • Acute or subacute ileus or chronic inflammatory bowel disease
  • Preexisting polyneuropathy > Grade I according to NCI-CTCAE v.4.0
  • Relevant comorbidities which might impair patient eligibility or safety for study participation like active infections, hepatic, renal or metabolic diseases
  • Clinically significant cardiovascular diseases within 12 months prior to study start (e.g. unstable angina pectoris, myocardial infarction, heart failure ≥ NYHA II, cardiac arrhythmias requiring treatment)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: RASH positive

Run-In-Phase during 4 weeks:

Gemcitabine 1000 mg/m², weekly Erlotinib 100 mg, weekly

Thereafter Treatment in patients with RASH-positve outcome after 4 weeks.
Drug: Gemcitabine
1000 mg/m² iv weekly
Other Names:
  • Gemzar
Drug: Erlotinib
100mg, once per day
Other Names:
  • Tarceva
Active Comparator: RASH-negative

Run-In-Phase during 4 weeks:

Gemcitabine 1000 mg/m², weekly Erlotinib 100 mg, weekly

RASH-negative patients quit treatment with Gemcitabine + Erlotinib and continue treatment with FOLFIRINOX:

Oxaliplatin 85mg/m2 Irinotecan 180 mg/m2 Folinic acid 400 mg/m2 5-FU 400 mg/m2 bolus iv 5-FU 2400 mg/m2 46-hours continous infusion
Drug: Oxaliplatin
85mg/m², q2weeks
Other Names:
  • Eloxatin
Drug: Folinic Acid
400 mg/m², q2weeks
Other Names:
  • Leucovorin
Drug: Irinotecan
180 mg/m², q2weeks
Other Names:
  • Campto
Drug: 5-FU
400 mg/m² Day 1; 2400 mg/m² 46 hour invusion, q2weeks
Other Names:
  • 5-Flourouracil

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
1-year Survial rate of "good-risk" patients
Time Frame: Follow-Up Phase (1.5 years)
1-year Survial rate of "good-risk" patients of patients under gemcitabine plus erlotinib with RASH
Follow-Up Phase (1.5 years)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Evalutation of overall response rate, disease control rate and progression free survival
Time Frame: Approximately 12 months

Evaluation of Parameters by RASH positve and negative patients:

  • ORR
  • DCR
  • PFS
  • OS
Approximately 12 months
Evaluation of adverse events
Time Frame: Treatment Phase (1.5 Years)
Assesment with NCI-CTCAE V4.0 Evalutation of side effects including picture documentation of skin-rash
Treatment Phase (1.5 Years)
Translational Projects
Time Frame: Approximately 24 months
  • Evaluation of Parameters for EGFR signal transduction
  • Evaluation Molecularbiological Parametrs of RASH
  • Picture Documentation of RASH. Corellation with clinical and molecularbiological Parameters
Approximately 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Ludwig-Maximilians - University of Munich

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Roche Pharma AG

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2012

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2015

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 23, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 13, 2012

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 20, 2012

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 19, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 16, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2011-005471-17

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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