Colorectal CancerPhase 2NCT01032291

A Study to Assess the Efficacy and Safety of Lenalidomide in Combination With Cetuximab in Pre-treated Patients With KRAS Mutant Colorectal Cancer

A Phase 2 study testing cetuximab and lenalidomide in people with Colorectal Cancer, run by Celgene Corporation at 17 sites in 6 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

The purpose of this study is to determine whether lenalidomide in combination with cetuximab is safe and effective in patients with KRAS mutant colorectal cancer. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Colorectal Cancer
What is being tested?: cetuximab and lenalidomide
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 51 participants
Where: 17 sitesin 6 countries
Study dates: Dec 2009to Jan 2011
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Metastatic colorectal adenocarcinoma.
Confirmed K-RAS mutant tumor
Disease progression on oxaliplatin- AND irinotecan-containing regimens, with at least one of these regimens containing bevacizumab.
Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1.

Who cannot join

Use of chemotherapy, hormonal therapy, immunotherapy or any other cancer or experimental treatment ≤ 28 days prior to the first day of the first cycle.
Radiotherapy for up to ≥ 30% of the bone marrow.
Surgery ≤ 28 days before day 1 of the first cycle (minimally invasive interventions for diagnostic purposes or disease staging are permitted).
Previous treatment with cetuximab, panitumumab, pomalidomide (CC-4047), lenalidomide or thalidomide.
Untreated, symptomatic brain metastases (brain imaging not required).
Venous thromboembolism ≤ 6 months before day1 of the first cycle.

Show all 9Show fewer

Current congestive heart failure (classes II to IV of the New York Heart Association).
Myocardial infarction ≤ 12 months before day1 of the first cycle.
Uncontrolled hypertension.

Trial locations and contacts

17 sites in 6 countries.

Country

City, postcode or hospital

17 sites in 6 countries

Belgium6 sites

UZ Antwerpen Dept. of Medical Oncology
Antwerp
ULB Erasme Service de Gastroenterologie
Brussels
Grand hôpital de Charleroi, Oncologie
Charleroi
Algemeen Ziekenhuis Maria Middelares
Ghent
Universitaire Ziekenhuis Gasthuisberg K.U. Leuven Gastroenterologie, Oncologie
Leuven
Centre Hospitalier Universitaire Sart Tilman Liège
Liège

Other trials in Belgium

Italy3 sites

Azienda Osperdaliero Universitaria Riuniti Umberto I-GM Lancisi-G. Salesi di Ancona Clinica di Oncologia Medica
Ancona
Azienda Ospedaliera Universitaria San Martino Unità Operativa Oncologia Medica
Genova
Azienda Ospedaliera Niguarda Ca' Grande, Oncologia Medica Falck
Milan

Other trials in Italy

Spain3 sites

Hospital Vall D'Hebron Servicio de Oncología. Unidad de ensayos clínicos
Barcelona
Hospital Universitario Marques de Valdecilla Servicio de Oncología
Santander
Hospital Clinico Universitario de Valencia Servicio de Oncologia
Valencia

Other trials in Spain

Sweden3 sites

Östra Sjukhuset Kirurgkliniken
Gothenburg
Karolinska University Hospital, Solna, Karolinska Institutet Dept of Oncology
Stockholm
Akademiska Sjukhuset Onkologkliniken
Uppsala

Other trials in Sweden

Australia1 site

Flinders Medical Centre, Dept. of Oncology
Bedford Park, South Australia

Other trials in Australia

Germany1 site

Klinikum Oldenburg gGmbH Klinik für Innere Medizin II
Oldenburg, Lower Saxony

Other trials in Germany

About this study

Official title: A Phase 2, Open-Label Study To Evaluate The Efficacy And Safety Of Lenalidomide In Combination With Cetuximab In Pretreated Subjects With K-Ras Mutant Metastatic Colorectal Cancer

The purpose of this study is to determine whether lenalidomide in combination with cetuximab is safe and effective in patients with KRAS mutant colorectal cancer.

Conditions: Colorectal Cancer
Being tested: cetuximab, lenalidomide
Keywords: Colorectal cancer, Revlimid, Lenalidomide, Cetuximab, Erbitux, KRAS
Medical subject headings: Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

cetuximabDrug
Also called Erbitux
Intravenous infusions of cetuximab (400 mg/m^2 Cycle 1 Day 1, thereafter 250 mg/m^2), administered on days 1, 8, 15 and 22 of each 28 day cycle.
lenalidomideDrug
Also called Revlimid
Daily oral lenalidomide 25mg on days 1 to 28 of each 28 day cycle

Study groups in NCT01032291
Study group	Role	What they receive
lenalidomide plus cetuximab	Experimental	Combination therapy of lenalidomide plus cetuximab Receives: Drug: cetuximab; Drug: lenalidomide
lenalidomide	Experimental	Single agent therapy of lenalidomide Receives: Drug: lenalidomide

What is being measured

The primary outcome is the main question the study is designed to answer.

Participants With Dose Limiting Toxicities (DLTs) During the First Treatment Cycle of the Safety Lead-In Period
The number of participants with DLTs determines the maximum tolerated dose of the combination therapy used in the Proof of Concept (POC) period:
If <2 of the initial 6 participants experience a DLT, then the POC will start with lenalidomide at 25 mg.
If ≥2 of the initial 6 participants experienced a DLT, then 6 more subjects were to be enrolled at 20 mg lenalidomide.
If <2 of the additional 6 subjects experienced a DLT, then the lenalidomide starting dose for the POC was to be 20 mg.
If ≥2 of the additional 6 subjects experienced a DLT, then 6 more subjects were to be enrolled at 15 mg lenalidomide.
If <2 of the additional 6 subjects experienced a DLT, then the POC was to start with lenalidomide at 15 mg.
If ≥2 of the additional 6 subjects experienced a DLT, the dosing for the study was to be reassessed by Celgene Corporation and the investigators.
Measured: Up to Day 28 (Cycle 1)
Percentage of Participants With a Response to Treatment During the Proof of Concept Period
Tumor response was evaluated every 2 cycles beginning with Cycle 3 Day 1 and at treatment discontinuation. Response and progression were evaluated using the RECIST 1.1 criteria (Eisenhauer, 2009).
Treatment response includes both complete response and partial response.
- Complete response-disappearance of all lesions
- Partial response-30% decrease in the sum of diameters of target lesions from baseline
Analysis was not performed due to the early termination of the study.
Measured: week 9 up to week 24

Secondary outcomes (5)

Kaplan-Meier Estimates for Progression Free Survival (PFS)
PFS was calculated as the time from randomization to the earlier of the first documentation of progressive disease (PD), or death on study due to any cause.
Analysis was not performed due to the early termination of the study.
Measured: up to week 24
Kaplan-Meier Estimates for Duration of Response
Duration of response was defined as the time from the initial response date to progressive disease (PD) for participants who achieved an objective confirmed complete response (CR) or partial response (PR).
Analysis was not performed due to the early termination of the study.
Measured: up to week 24
Percentage of Participants With Disease Control
Known as the Disease Control Rate (DCR), participants with a complete response, partial response or stable disease contribute to the DCR.
This analysis was not performed due to the early termination of the study.
Measured: up to week 24
Kaplan-Meier Estimates for Overall Survival
Overall survival was defined as the time between randomization and death. It was intended that participants would be followed for up to 5 years following discontinuation from treatment.
Analysis was not performed due to the early termination of the study.
Measured: up to 5.5 years
Participants With Treatment-Emergent Adverse Events (TEAE)
TEAEs are any adverse event occurring or worsening on or after the first treatment of any study drug and within 28 days after the last dose of the last study drug received. Relation to study drug was determined by the investigator. Severity of AE is graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.0. Severity is a 5-point scale: 3= severe or medically significant but not life-threatening 4=life-threatening, urgent intervention required 5=death related to AE.
Measured: up to week 28

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Dec 2009Jan 2011

First posted15 Dec 2009 (estimated)
Study startDec 2009
Primary completionJan 2011
Study completionJan 2011

Why it stopped: A business decision not to continue with Phase 2b based on non-safety observations during proof of concept phase.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Colorectal CancerStudies 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 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 51 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01032291
Sponsor's protocol ID: CC-5013-COLO-001
Other IDs: 2009-012665-61, 2009
Status last verified: Apr 2013
First submitted: 14 Dec 2009
Last updated: 21 May 2013
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Gandhi AK, Shi T, Li M, Jungnelius U, Romano A, Tabernero J, Siena S, Schafer PH, Chopra R. Immunomodulatory effects in a phase II study of lenalidomide combined with cetuximab in refractory KRAS-mutant metastatic colorectal cancer patients. PLoS One. 2013 Nov 11;8(11):e80437. doi: 10.1371/journal.pone.0080437. eCollection 2013.
PubMed 24244687
Siena S, Van Cutsem E, Li M, Jungnelius U, Romano A, Beck R, Bencardino K, Elez ME, Prenen H, Sanchis M, Sartore-Bianchi A, Tejpar S, Gandhi A, Shi T, Tabernero J. Phase II open-label study to assess efficacy and safety of lenalidomide in combination with cetuximab in KRAS-mutant metastatic colorectal cancer. PLoS One. 2013 Nov 11;8(11):e62264. doi: 10.1371/journal.pone.0062264. eCollection 2013.
PubMed 24244261

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 21 May 2013. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 2, Open-Label Study To Evaluate The Efficacy And Safety Of Lenalidomide In Combination With Cetuximab In Pretreated Subjects With K-Ras Mutant Metastatic Colorectal Cancer
ClinicalTrials.gov ID: NCT01032291
Acronym / sponsor ID: CC-5013-COLO-001
Conditions: Colorectal Cancer
Keywords: Colorectal cancer, Revlimid, Lenalidomide, Cetuximab, Erbitux, KRAS
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: A business decision not to continue with Phase 2b based on non-safety observations during proof of concept phase.
Enrolment: 51 participants (actual)
Lead sponsor: Celgene CorporationIndustry (pharma, biotech, devices)
Study start: Dec 2009
Primary completion: Jan 2011 (actual)
Study completion: Jan 2011 (actual)
First posted: 15 Dec 2009 (estimated)
Results: Posted 21 May 2013

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 determine whether lenalidomide in combination with cetuximab is safe and effective in patients with KRAS mutant colorectal cancer.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
lenalidomide plus cetuximab	Experimental	Drug: cetuximab, Drug: lenalidomideCombination therapy of lenalidomide plus cetuximab
lenalidomide	Experimental	Drug: lenalidomideSingle agent therapy of lenalidomide

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

Metastatic colorectal adenocarcinoma.
Confirmed K-RAS mutant tumor
Disease progression on oxaliplatin- AND irinotecan-containing regimens, with at least one of these regimens containing bevacizumab.
Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1.

Key exclusion criteria (9 listed)

Use of chemotherapy, hormonal therapy, immunotherapy or any other cancer or experimental treatment ≤ 28 days prior to the first day of the first cycle.
Radiotherapy for up to ≥ 30% of the bone marrow.
Surgery ≤ 28 days before day 1 of the first cycle (minimally invasive interventions for diagnostic purposes or disease staging are permitted).
Previous treatment with cetuximab, panitumumab, pomalidomide (CC-4047), lenalidomide or thalidomide.
Untreated, symptomatic brain metastases (brain imaging not required).

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
cetuximabAlso: ErbituxIntravenous infusions of cetuximab (400 mg/m^2 Cycle 1 Day 1, thereafter 250 mg/m^2), administered on days 1, 8, 15 and 22 of each 28 day cycle.	Drug	lenalidomide plus cetuximab
lenalidomideAlso: RevlimidDaily oral lenalidomide 25mg on days 1 to 28 of each 28 day cycle	Drug	lenalidomide, lenalidomide plus cetuximab

Primary outcome

Participants With Dose Limiting Toxicities (DLTs) During the First Treatment Cycle of the Safety Lead-In Period
Time frame: Up to Day 28 (Cycle 1)
The number of participants with DLTs determines the maximum tolerated dose of the combination therapy used in the Proof of Concept (POC) period: If <2 of the initial 6 participants experience a DLT, then the POC will start with lenalidomide at 25 mg. If ≥2 of the initial 6 participants experienced a DLT, then 6 more subjects were to be enrolled at 20 mg lenalidomide. If <2 of the additional 6 subjects experienced a DLT, then the lenalidomide starting dose for the POC was to be 20 mg. If ≥2 of the additional 6 subjects experienced a DLT, then 6 more subjects were to be enrolled at 15 mg lenalidomide. If <2 of the additional 6 subjects experienced a DLT, then the POC was to start with lenalidomide at 15 mg. If ≥2 of the additional 6 subjects experienced a DLT, the dosing for the study was to be reassessed by Celgene Corporation and the investigators.
Percentage of Participants With a Response to Treatment During the Proof of Concept Period
Time frame: week 9 up to week 24
Tumor response was evaluated every 2 cycles beginning with Cycle 3 Day 1 and at treatment discontinuation. Response and progression were evaluated using the RECIST 1.1 criteria (Eisenhauer, 2009). Treatment response includes both complete response and partial response. * Complete response-disappearance of all lesions * Partial response-30% decrease in the sum of diameters of target lesions from baseline Analysis was not performed due to the early termination of the study.

5 secondary outcomes

Kaplan-Meier Estimates for Progression Free Survival (PFS)
Time frame: up to week 24
Kaplan-Meier Estimates for Duration of Response
Time frame: up to week 24
Percentage of Participants With Disease Control
Time frame: up to week 24
Kaplan-Meier Estimates for Overall Survival
Time frame: up to 5.5 years
Participants With Treatment-Emergent Adverse Events (TEAE)
Time frame: up to week 28

Results and safety

Results posted to the registry on 21 May 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Lenalidomide + Cetuximab (Safety Lead-in)	8	6
Lenalidomide (Proof of Concept)	0	0
Lenalidomide + Cetuximab (Proof of Concept)	0	0

Primary outcome: Participants With Dose Limiting Toxicities (DLTs) During the First Treatment Cycle of the Safety Lead-In Period

Time frame: Up to Day 28 (Cycle 1). Number. Unit: participants

Measure	Lenalidomide Plus Cetuximab (Safety Lead-in) n = 8
Value	1

Population analysed: All participants who took at least one dose of study medication. If a participant discontinued the study prior to completing the entire first cycle for reasons other than a DLT or if ≥7 days of lenalidomide and/or ≥1 dose of cetuximab were missed during the first cycle for reasons other than a DLT, a replacement would be added at that dose level.

Primary outcome: Percentage of Participants With a Response to Treatment During the Proof of Concept Period

Time frame: week 9 up to week 24

Population analysed: Efficacy Evaluable Population. Analysis was not performed due to the early termination of the study.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: up to 28 weeks.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Lenalidomide (Proof of Concept)	9 of 21 (42.9%)	16 of 21 (76.2%)	Not reported
Lenalidomide + Cetuximab (Safety Lead-in and Proof of Concept)	14 of 29 (48.3%)	29 of 29 (100%)	Not reported

Limitations and caveats (from the sponsor): Enrollment stopped prematurely due to lack of efficacy and failure to achieve the planned response objective.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 May 2013.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 24244687Gandhi AK, Shi T, Li M, Jungnelius U, Romano A, Tabernero J, Siena S, Schafer PH, Chopra R. Immunomodulatory effects in a phase II study of lenalidomide combined with cetuximab in refractory KRAS-mutant metastatic colorectal cancer patients. PLoS One. 2013 Nov 11;8(11):e80437. doi: 10.1371/journal.pone.0080437. eCollection 2013.
Derived from this study: PubMed 24244261Siena S, Van Cutsem E, Li M, Jungnelius U, Romano A, Beck R, Bencardino K, Elez ME, Prenen H, Sanchis M, Sartore-Bianchi A, Tejpar S, Gandhi A, Shi T, Tabernero J. Phase II open-label study to assess efficacy and safety of lenalidomide in combination with cetuximab in KRAS-mutant metastatic colorectal cancer. PLoS One. 2013 Nov 11;8(11):e62264. doi: 10.1371/journal.pone.0062264. eCollection 2013.

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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.

Eric Van Cutsem, M.D., Ph,D principal investigator

Universitaire Ziekenhuis Gasthuisberg K.U. Leuven, Belgium

Josep Tabernero, M.D. principal investigator

Hospital Vall d´Hebrón, Servicio de Oncología, Barcelona. Spain

17 sites in 6 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing cetuximab and lenalidomide in people with Colorectal Cancer, run by Celgene Corporation at 17 sites in 6 countries.

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 4 inclusion and 9 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: stopped early, as of the sponsor's last update on 21 May 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in Belgium, Italy, Spain, Sweden, Australia and 1 more country. 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 phase mean?

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?

Yes. Results are posted in the registry (first posted 21 May 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Participants With Dose Limiting Toxicities (DLTs) During the First Treatment Cycle of the Safety Lead-In Period (time frame: Up to Day 28 (Cycle 1)). 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 NCT01032291, 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 21 May 2013.