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

NCT01547260 | Completed Phase 1 DMC

• 1 other identifier: LENAGEM-PANC
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Pancreatic Carcinoma Metastatic; Pancreatic Ductal Adenocarcinoma

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Within the first day of treatment until 60 days after start of treatment.

Secondary Outcomes (1)

• Clinical efficacy

  Within start of treatment until start of therapy until clinical and/or radiological signs of progression of the disease by treatment group together.

Study Arms (2)

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.

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.

Drug: Revlimid

Interventions

Gemzar DRUG

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).

Also known as: Revlimid

Lenalidomide

Revlimid DRUG

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.

Also known as: Gemzar

gemcitabine

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Maria Liljefors: lead
• Karolinska University Hospital: collaborator
• Karolinska Institutet: collaborator
• Celgene: collaborator

Study Sites (1)

Karolinska University Hospital

Stockholm, Solna, 171 76, Sweden

Location

Related Publications (2)

• 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.

  PMID: 28099502 DERIVED

• Ullenhag 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.

  PMID: 25837499 DERIVED

MeSH Terms

Interventions

Gemcitabine; Lenalidomide

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Håkan Mellstedt, Prof.

  Karolinska University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, Senior consultant

Study Record Dates

• First Submitted: February 28, 2012
• First Posted: March 7, 2012
• Study Start: October 1, 2009
• Primary Completion: January 1, 2014
• Study Completion: November 1, 2014
• Last Updated: August 22, 2022

Record last verified: 2022-08

Locations

SE (1)