Pancreatic Carcinoma MetastaticPhase 1/2LENAGEMNCT01547260
Lenalidomide and Gemcitabine as First-line Treatment in Patients With Pancreatic Cancer
A Phase 1/2 study testing Gemzar and Revlimid in people with Pancreatic Carcinoma Metastatic and Pancreatic Ductal Adenocarcinoma, run by Maria Liljefors at 1 site in Sweden.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Pancreatic Carcinoma Metastatic, Pancreatic Ductal Adenocarcinoma
- What is being tested?
- Gemzar and Revlimid
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteSweden
- Study dates
- Oct 2009to Nov 2014
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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).
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Being tested
- Gemzar, Revlimid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GemzarDrug
Also called Revlimid
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).
RevlimidDrug
Also called Gemzar
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.
| Study group | Role | What they receive |
|---|---|---|
| Lenalidomide | Experimental | 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. Receives: Drug: Gemzar |
| gemcitabine | Experimental | 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. Receives: Drug: Revlimid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety (phase I).
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.
Measured: Within the first day after start of treatment until 30 days post the last dose of study drug.
Immunomodulatory effect (phase II).
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.
Measured: Within the first day of treatment until 60 days after start of treatment.
Secondary outcomes (1)
Clinical efficacy
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.
Measured: Within start of treatment until start of therapy until clinical and/or radiological signs of progression of the disease by treatment group together.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2012 (estimated)
- Study startOct 2009
- Primary completionJan 2014
- Study completionNov 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Pancreatic Carcinoma MetastaticStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maria Liljefors
- Sponsor type
- University, hospital or other
- Collaborators
- Karolinska University Hospital, Karolinska Institutet, Celgene
- Responsible party
- Sponsor-investigator, Maria Liljefors, Karolinska University Hospital
- Investigators
- Håkan Mellstedt, Prof., Principal investigator, Karolinska University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01547260
- Sponsor's protocol ID
- LENAGEM-PANC
- Acronym
- LENAGEM
- Status last verified
- Aug 2022
- First submitted
- 28 Feb 2012
- Last updated
- 22 Aug 2022
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Ullenhag GJ, Mozaffari F, Broberg M, Mellstedt H, Liljefors M. Clinical and Immune Effects of Lenalidomide in Combination with Gemcitabine in Patients with Advanced Pancreatic Cancer. PLoS One. 2017 Jan 18;12(1):e0169736. doi: 10.1371/journal.pone.0169736. eCollection 2017.
PubMed 28099502Ullenhag GJ, Rossmann E, Liljefors M. A phase I dose-escalation study of lenalidomide in combination with gemcitabine in patients with advanced pancreatic cancer. PLoS One. 2015 Apr 2;10(4):e0121197. doi: 10.1371/journal.pone.0121197. eCollection 2015.
PubMed 25837499
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study of Lenalidomide and Gemcitabine as First-line Treatment in Patients With Locally Advanced or Metastatic Pancreatic Cancer
- ClinicalTrials.gov ID
- NCT01547260
- Acronym / sponsor ID
- LENAGEM / LENAGEM-PANC
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Maria LiljeforsUniversity, hospital or other
- Collaborators
- Karolinska University Hospital, Karolinska Institutet, Celgene
- Study start
- Oct 2009
- Primary completion
- Jan 2014 (actual)
- Study completion
- Nov 2014 (actual)
- First posted
- 7 Mar 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Lenalidomide | Experimental | Drug: GemzarPhase 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. |
| gemcitabine | Experimental | Drug: RevlimidGemcitabine, 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. |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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.
Key exclusion criteria (11 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GemzarAlso: RevlimidGemcitabine (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). | Drug | Lenalidomide |
| RevlimidAlso: GemzarLenalidomide 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. | Drug | gemcitabine |
Primary outcome
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.
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.
1 secondary outcome
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2022.
- Derived from this study: PubMed 28099502Ullenhag GJ, Mozaffari F, Broberg M, Mellstedt H, Liljefors M. Clinical and Immune Effects of Lenalidomide in Combination with Gemcitabine in Patients with Advanced Pancreatic Cancer. PLoS One. 2017 Jan 18;12(1):e0169736. doi: 10.1371/journal.pone.0169736. eCollection 2017.
- Derived from this study: PubMed 25837499Ullenhag GJ, Rossmann E, Liljefors M. A phase I dose-escalation study of lenalidomide in combination with gemcitabine in patients with advanced pancreatic cancer. PLoS One. 2015 Apr 2;10(4):e0121197. doi: 10.1371/journal.pone.0121197. eCollection 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Håkan Mellstedt, Prof. principal investigator
Karolinska University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Gemzar and Revlimid in people with Pancreatic Carcinoma Metastatic and Pancreatic Ductal Adenocarcinoma, run by Maria Liljefors at 1 site in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety (phase I). (time frame: Within the first day after start of treatment until 30 days post the last dose of study drug.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01547260, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2022.