Lenalidomide and Gemcitabine as First-line Treatment in Patients With Pancreatic Cancer (LENAGEM)

August 18, 2022 updated by: Maria Liljefors

Phase I/II Study of Lenalidomide and Gemcitabine as First-line Treatment in Patients With Locally Advanced or Metastatic Pancreatic Cancer

The purpose of this study is to ascertain whether treatment with lenalidomide or lenalidomide in combination with gemcitabine induces modulation of immune effector functions and to characterize the nature of immune functions.

Study Overview

Status

Status

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

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

Pancreatic cancer is characterised by aggressive growth, treatment resistance and an extremely poor prognosis. In subjects with locally advanced or metastatic disease, the median survival is approximately 6 - 11 months and 2 - 6 months, respectively. The currently accepted treatment for this disease in EU is gemcitabine which supplanted treatment with 5-FU after it was shown that median survival duration was marginally improved (4.41 and 5.65 months respectively, p = 0,022). The reported median survival time for subjects treated with single-agent gemcitabine in randomized phase III studies ranged form 4.9 to 7.2 months. Despite these improvements in the treatment of pancreatic cancer, the prognosis remains very poor. Lenalidomide (Revlimid®) belongs to a proprietary class of compounds called immunomodulatory drugs (IMiDs). IMiDshave both immunomodulatory and anti-angiogenic properties which could confer antitumour and antimetastatic effects. Lenalidomide has been demonstrated to possess anti-angiogenic activity through inhibition of bFGF, VEGF and TNF-alpha induced endothelial cell migration, due at least in part to inhibition of Akt phosphorylation response to bFGF.In addition, lenalidomide has a variety of immunomodulatory effects. Gemcitabine (Gemzar®) is a synthetic pyrimidine nucleoside analogue that is used as standard treatment of advanced pancreatic cancer. Beside the cytotoxic activity of gemcitabine, accumulating evidence has indicated that the product promote specific anticancer immune responses that contribute to the therapeutic effects of conventional therapy.Down-regulation in survival rate of pancreatic cell lines has more recently been observed, when treated with lenalidomide and gemcitabine in sub-optimal concentrations.Those data supports a hypothesis of a potential hyper-additive affect of the treatments given in combination. Therefore lenalidomide and gemcitabine should be of major interest to explore for combination therapy.

This is a phase I/II open-label, multi-center study. It will consist of a phase I dose-finding part and a phase II part during which subjects will be treated at the MTD established during phase I. Lenalidomide will be administered by a stepwise dose-escalation schedule in the phase I part. Thus, the primary endpoint in the phase I part is to determine the MTD and safety of the regimen lenalidomide and gemcitabine as first-line treatment in subjects with advanced pancreatic cancer.In the phase II part, primary endpoint is to evaluate the immunomodulatory effects of lenalidomide in combination with gemcitabine in the same patient population.

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.
34

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
  • Phase 1

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

  • Sweden
    • Solna
      • Stockholm, Solna, Sweden, 171 76
        • Karolinska University Hospital

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

19 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologically or cytologically confirmed, unresectable, locally advanced, or metastatic adenocarcinoma of the pancreas.
  • ECOG performance status of 0 or 1, see Appendix 1.
  • Life expectancy > 12 weeks.
  • Must understand and voluntarily sign an informed consent form.
  • Age > 18 years at the time of signing informed consent form.
  • Must be able to adhere to the study visit schedule and other protocol requirements.

  • Female subjects of childbearing potential† must:

    • Understand that the study medication is expected to have a teratogenic risk
    • Agree to use, and be able to comply with, effective contraception without interruption, 4 weeks before starting study drug, throughout study drug therapy (including dose interruptions) and for 4 weeks after the end of study drug therapy, even if she has amenorrhoea

  • Male subjects must:

    • Agree to use condoms throughout study drug therapy, during any dose interruption and for one week after cessation of study therapy if their partner is of childbearing potential and has no contraception.
    • Agree not to donate semen during study drug therapy and for one week after end of study drug therapy

Exclusion Criteria:

  • Prior use of systemic chemotherapy for the treatment of adenocarcinoma of the pancreas (with the exception of gemcitabine, fluorouracil, or capecitabine in the adjuvant setting).
  • Laboratory abnormalities:
  • Prior history of malignancy within 5 years (except basal or squamous cell carcinoma or carcinoma in situ of the cervix or breast, localized prostate cancer with PSA < 1,0 mg/dL).
  • Subjects with a history of or active DVT or PE that are not therapeutically managed on a stable dose of appropriate anticoagulant.
  • Brain metastases (subjects that are asymptomatic and do not require steroid control may be enrolled at the discretion of the investigator).
  • Surgery within 28 days prior to cycle 1 Day 1 (minimally invasive procedures for the purpose of diagnosis or staging of the disease are permitted, including stent placement and insertion of central venous access advice).
  • Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
  • Any serious medical condition or psychiatric illness that places the subject at an unacceptable risk for study participation or would prevent the subject from signing the informed consent form.
  • Prior therapy with lenalidomide or thalidomide.
  • Use of any other experimental drug or therapy within 28 days prior to Cycle 1 Day 1.
  • Pregnant or lactating females.

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: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

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: Lenalidomide
Phase I; Lenalidomide capsules will be taken orally each day on days 1-21 of each 28-day cycle. 3 subjects will be enrolled into each dose cohort for 15, 20 and 25 mg/day. Gemcitabine, 1000 mg/m2 in 0.9% sodium chloride will be administered iv over 30 minutes, at days 1, 8, 15 of each 28-day cycle. Phase II: Every other consecutive included subject in phase II part will be treated with either single lenalidomide (days 1-21 of 28) or single gemcitabine (days 1, 8, 15 of 28) during Cycle 1. The first included patient in phase II part will start with single lenalidomide. From treatment cycle number 2 and beyond, all subjects in the phase II part of the study will be treated with lenalidomide in combination with gemcitabine.
Drug: Gemzar
Gemcitabine (Gemzar®), 1000 mg/m2 in 0.9% sodium chloride will be administered as intravenous infusion over 30 minutes, weekly for 3 weeks then rest for 1 week (days 1, 8, 15 of each 28-day cycle).
Other Names:
  • Revlimid
EXPERIMENTAL: gemcitabine
Gemcitabine, 1000 mg/m2 in 0.9% sodium chloride will be administered iv over 30 minutes, at days 1, 8, 15 of each 28-day cycle in both phase I and II. Phase I:Lenalidomide capsules will be taken orally each day on days 1-21 of each 28-day cycle. 3 subjects will be enrolled into each dose cohort for 15, 20 and 25 mg/day. Phase II: Every other consecutive included subject in phase II part will be treated with either single lenalidomide (days 1-21 of 28) or single gemcitabine (days 1, 8, 15 of 28) during Cycle 1. The first included patient in phase II part will start with single lenalidomide. From treatment cycle number 2 and beyond, all subjects in the phase II part of the study will be treated with lenalidomide in combination with gemcitabine.
Drug: Revlimid
Lenalidomide capsules will be taken orally in the morning each day on days 1-21 of each 28-day cycle. Phase I; Three subjects will be enrolled into each dose cohort for 15, 20 and 25 mg/day, respectively. Phase II; Lenalidomide at dose determined in Phase I, will be administered orally once daily for 21 days followed by 7 days rest.
Other Names:
  • Gemzar

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
Safety (phase I).
Time Frame: Within the first day after start of treatment until 30 days post the last dose of study drug.
In the phase I part of the study, the primary outcome is to determine the MTD and safety of the regimen lenalidomide and gemcitabine in combination. Data from all subjects who receive any study drug will be included in the safety analyses, according to the NCI CTCAE v3.0.
Within the first day after start of treatment until 30 days post the last dose of study drug.
Immunomodulatory effect (phase II).
Time Frame: Within the first day of treatment until 60 days after start of treatment.
In the phase II part, the primary endpoint is to evaluate assessment of immunological reaction.The changes in immune responses at the end of cycle 1 (single lenalidomide or single gemcitabine) and cycle 2 (lenalidomide combined with gemcitabine) will be described in relation to baseline within the individual patient.
Within the first day of treatment until 60 days after start of treatment.

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
Clinical efficacy
Time Frame: Within start of treatment until start of therapy until clinical and/or radiological signs of progression of the disease by treatment group together.

Progression-free survival (PFS) will be presented as time from start of therapy until clinical and/or radiological signs of progression of the disease by treatment group together.

Survival rate at 12 months will be presented as rate of patients still alive at 12 months after start of therapy by treatment group together.

Overall survival (OS) will be presented as time from start of therapy until death by treatment group together.
Within start of treatment until start of therapy until clinical and/or radiological signs of progression of the disease by treatment group together.

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.
Maria Liljefors

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.
Karolinska University Hospital
Karolinska Institutet
Celgene

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Håkan Mellstedt, Prof., Karolinska University Hospital

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

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.
October 1, 2009

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.
January 1, 2014

Study Completion (ACTUAL)

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.
November 1, 2014

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).
February 28, 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.
March 2, 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.
March 7, 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.
August 22, 2022

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.
August 18, 2022

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.
August 1, 2022

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.
  • LENAGEM-PANC

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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