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

Phase 1/Phase 2
19 Years
Open (Enrolling)
Pancreatic Carcinoma.

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Trial Information

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

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.

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.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safety (phase I).

Outcome Description:

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.

Outcome Time Frame:

Within the first day after start of treatment until 30 days post the last dose of study drug.

Safety Issue:


Principal Investigator

Håkan Mellstedt, Prof.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Karolinska University Hospital


Sweden: Medical Products Agency

Study ID:




Start Date:

October 2009

Completion Date:

January 2014

Related Keywords:

  • Pancreatic Carcinoma.
  • Carcinoma
  • Pancreatic Neoplasms