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Squamous Cell CancerPhase 1/2ADVANTAGENCT00705016

Cilengitide in Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN)

A Phase 1/2 study testing Cilengitide 2000 mg once weekly, Cilengitide 2000 mg twice weekly and Cetuximab in people with Squamous Cell Cancer, run by Merck KGaA, Darmstadt, Germany at 37 sites in 9 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this open-label, randomized, controlled, Phase 1/2 study of the integrin inhibitor cilengitide is to evaluate the safety and efficacy of the combination of different regimens of cilengitide added to cisplatin, 5-fluorouracil (5-FU), and cetuximab in participants with recurrent/metastatic squamous cell… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Squamous Cell Cancer
What is being tested?
Cilengitide 2000 mg once weekly, Cilengitide 2000 mg twice weekly and Cetuximab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
184 participants
Where
37 sitesin 9 countries
Study dates
Oct 2008to Jun 2013
Phase
Phase 1/2
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

  • Histologically or cytologically confirmed diagnosis of SCCHN
  • At least one measurable lesion either by computerized tomography (CT) scan or magnetic resonance imaging (MRI)
  • Karnofsky performance status (KPS) of greater than or equal to 70 or eastern cooperative oncology group performance status (ECOG PS) of 0-1 at trial entry

Who cannot join

  • Prior systemic chemotherapy, except if given as part of a multimodal treatment for locally advanced disease, which was completed more than 6 months prior to trial entry
  • Surgery (excluding prior diagnostic biopsy) or irradiation within 4 weeks before trial entry
  • Nasopharyngeal Carcinoma
  • Documented or symptomatic brain or leptomeningeal metastasis
  • Previous treatment with epidermal growth factor receptor (EGFR) targeting therapy or signal transduction inhibitors

Trial locations and contacts

37 sites in 9 countries.

37 sites in 9 countries

Germany9 sites
  • Research Site

    Aachen

  • Research Site

    Berlin

  • Research Site

    Essen

  • Research Site

    Hamburg

  • Research Site

    Heidelberg

  • Research Site

    Jena

  • Research Site

    Leipzig

  • Research Site

    Rostock

  • Research Site

    Stuttgart

Other trials in Germany

France7 sites
  • Research Site

    Lille

  • Research Site

    Montpellier

  • Research Site

    Nice

  • Research Site

    Toulouse

  • Research Site

    Tours

  • Research Site

    Vandœuvre-lès-Nancy

  • Research Site

    Villejuif

Other trials in France

Belgium6 sites
  • Research Site

    Antwerp

  • Research Site

    Brussels

  • Research Site

    Edegem (Antwerp)

  • Research Site

    Ghent

  • Research Site

    Leuven

  • Research Site

    Namur

Other trials in Belgium

Hungary3 sites
  • Research Site

    Budapest

  • Research Site

    Győr

  • Research Site

    Nyíregyháza

Other trials in Hungary

Italy3 sites
  • Research Site

    La Spezia

  • Research Site

    Milan

  • Research Site

    Naples

Other trials in Italy

Spain3 sites
  • Research Site

    L'Hospitalet de Llobregat

  • Research Site

    Madrid

  • Research Site

    Velencia

Other trials in Spain

Austria2 sites
  • Research Site

    Salzburg

  • Research Site

    Vienna

Other trials in Austria

Poland2 sites
  • Research Site

    Gliwice

  • Research Site

    Warsaw

Other trials in Poland

Switzerland2 sites
  • Research Site

    Basel

  • Research Site

    Geneva

Other trials in Switzerland

About this study

Official title: Open-label, Randomized, Controlled Phase I/II Study of Cilengitide to Evaluate the Safety and Efficacy of the Combination of Different Regimens of Cilengitide Added to Cisplatin, 5-FU, and Cetuximab in Subjects With Recurrent/Metastatic Squamous Cell Cancer of the Head and Neck

The purpose of this open-label, randomized, controlled, Phase 1/2 study of the integrin inhibitor cilengitide is to evaluate the safety and efficacy of the combination of different regimens of cilengitide added to cisplatin, 5-fluorouracil (5-FU), and cetuximab in participants with recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN).

The Phase 1 part was conducted in dedicated study centers. In the Phase 2 part of this trial, cilengitide is administered at two different doses to two experimental groups. The third group will only receive cisplatin, 5-FU and cetuximab. In the Phase 1 part of this trial, the dose of cilengitide in combination with cisplatin, 5-FU and cetuximab was determined.

Read more

Cilengitide is an experimental anti-cancer substance interacting with so-called integrins. Integrins are protein molecules that are known to be present on the surface of certain cancer cells. Integrins are also found on certain cells that belong to growing blood vessels (endothelial cells). Integrins potentially facilitate the blood vessels' support of the tumor (angiogenesis) as well as the tumor's growth and further spread throughout the body (metastasis). By inhibiting integrins on the tumor cell surface, cilengitide potentially kills cancer cells, and potentially sensitizes cancer cells to other co-administered therapeutics. By inhibiting integrins on the endothelial cell surface, it potentially inhibits the ingrowth of additional blood vessels towards the tumor.

Cilengitide is given as an intravenous infusion (given by a drip in one vein of your arm). If any unacceptable side effect occurs, treatment with the study drug will be stopped.

Being tested
Cilengitide 2000 mg once weekly, Cilengitide 2000 mg twice weekly, Cetuximab, 5-fluorouracil (5-FU), Cisplatin
Keywords
Randomized treatment, open-label, controlled, recurrent, metastatic, SCCHN, suitable, for local therapy
Medical subject headings
Neoplasms, Squamous Cell, Recurrence, Neoplasm Metastasis

What participants receive

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

  • Cilengitide 2000 mg once weeklyDrug

    Cilengitide 500 milligram (mg) will be administered as an intravenous infusion over 60 minutes, daily from Day 1 to 4 of the first week of each 3-week cycle, subsequently followed by 2000 mg dose of cilengitide on Day 8 and 15 of every cycle for a total of 6 cycles (18 weeks) or until PD, unacceptable toxicity or withdrawal for any other reason. After 6 cycles, participants received cilengitide 2000 mg once weekly until PD, unacceptable toxicity or withdrawal for any other reason.

  • Cilengitide 2000 mg twice weeklyDrug

    Cilengitide 2000 mg will be administered as an intravenous infusion over 60 minutes, twice weekly on Day 1, 4, 8, 11, 15, and 18 of each 3-week cycle for a total of 6 cycles (18 weeks) or until PD, unacceptable toxicity or withdrawal for any other reason. After 6 cycles, participants will receive cilengitide 2000 mg once weekly until PD, unacceptable toxicity or withdrawal for any other reason.

  • CetuximabDrug

    Also called Erbitux®

    Cetuximab will be administered as 250 milligram per square meter (mg/m^2) as infusion (initial starting dose of 400 mg/m^2) on Day 1, 8 and 15 of each 3-week treatment cycle. Cetuximab will be administered for a total of 6 cycles (18 weeks) or until PD, unacceptable toxicity or withdrawal for any other reason. After 6 cycles, participants received Cetuximab 250 mg/m^2 once weekly until PD, unacceptable toxicity or withdrawal for any other reason.

  • 5-fluorouracil (5-FU)Drug

    5-FU will be administered as an intravenous continuous infusion at a dose of 1000 mg/m^2 daily from Day 1 to 4 of each 3-week treatment cycle. 5-FU will be administered for a total of 6 cycles (18 weeks), or until PD, unacceptable toxicity, or withdrawal for any other reason, whichever occur first.

  • CisplatinDrug

    Cisplatin will be administered as an intravenous infusion over 60 minutes, at a dose 100 mg/m^2 on Day 1 of each 3-week treatment cycle. Cisplatin will be administered for a total of 6 cycles (18 weeks), or until PD, unacceptable toxicity, or withdrawal for any other reason, whichever occur first.

Study groups in NCT00705016
Study groupRoleWhat they receive
Cilengitide 2000 mg once weekly+Cetuximab+5-FU+CisplatinExperimentalNot described
Receives: Drug: Cilengitide 2000 mg once weekly; Drug: Cetuximab; Drug: 5-fluorouracil (5-FU); Drug: Cisplatin
Cilengitide 2000 mg twice weekly+Cetuximab+5-FU+CisplatinExperimentalNot described
Receives: Drug: Cilengitide 2000 mg twice weekly; Drug: Cetuximab; Drug: 5-fluorouracil (5-FU); Drug: Cisplatin
Cetuximab+5-FU+CisplatinActive comparatorNot described
Receives: Drug: Cetuximab; Drug: 5-fluorouracil (5-FU); Drug: Cisplatin

What is being measured

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

  1. Progression-free Survival (PFS) Time: Investigator Read

    The PFS is defined as the duration from randomization until radiological progression (based on response evaluation criteria in solid tumors [RECIST] Version 1.0) or death due to any cause. Only deaths within 84 days of last tumor assessment are considered. Participants without event are censored on the date of last tumor assessment. Investigator read is the assessment of all imaging by the treating physician at the local trial site.

    Measured: Time from randomization to disease progression, death or last tumor assessment, reported between day of first participant randomized, 03 July 2009, until cut-off date (03 September 2011)

Secondary outcomes (6)
  1. Overall Survival (OS) Time

    The OS time is defined as the time from randomization to death. Participants without event are censored at the last date known to be alive or at the clinical cut-off date, whichever is earlier.

    Measured: Time from randomization to death, reported between day of first participant randomized, 03 July 2009, until cut-off date (03 September 2011)

  2. Best Overall Response (BOR) Rate

    The BOR rate is defined as the percentage of the participants having achieved confirmed complete response (CR) or partial response (PR) as the best overall response according to radiological assessments (based on RECIST Version 1.0).

    Measured: Evaluations will be performed every 6 weeks until progression reported between day of first participant randomized, 03 July 2009, until cut-off date (03 September 2011)

  3. Disease Control Rate

    The disease control rate is defined as the percentage of participants having achieved confirmed CR, PR or stable disease (SD) as best overall response according to radiological assessments (based on RECIST Version 1.0).

    Measured: Evaluations will be performed every 6 weeks until progression reported between day of first participant randomized, 03 July 2009, until cut-off date (03 September 2011)

  4. Time to Treatment Failure (TTF)

    TTF is defined as the time from randomization to date of the first occurrence of; progression, discontinuation of treatment due to progression or adverse event, start of new anticancer therapy, withdrawal of consent, or death (within 84 days of last tumor assessment). Participants without event are censored on the date of last tumor assessment.

    Measured: Time from randomization to disease progression, death or last tumor assessment, reported between day of first participant randomized, 03 July 2009, until cut-off date (03 September 2011)

  5. Duration of Response

    Duration of response is defined as the time from the first assessment of CR or PR until the date of the first occurrence of progressive disease (PD), or until the date of death.

    Measured: Time from first assessment of CR or PR until PD, death or last tumor assessment, reported between day of first participant randomized, 03 July 2009, until cut-off date (03 September 2011)

  6. Safety - Number of Participants Experiencing Any Adverse Event

    Please refer to Adverse Events section for details of individual serious adverse events and other adverse events

    Measured: Time from first assessment of CR or PR until PD, death or last tumor assessment, reported between day of first participant randomized, 03 July 2009, until cut-off date (03 September 2011)

Timeline

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

  1. First posted25 Jun 2008 (estimated)
  2. Study startOct 2008
  3. Primary completionSep 2011
  4. Study completionJun 2013

Resources

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
184 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00705016
Sponsor's protocol ID
EMR 200052-013
Other IDs
2008-000615-15, 2008
Acronym
ADVANTAGE
Status last verified
Mar 2014
First submitted
24 Jun 2008
Last updated
30 Apr 2014
Data monitoring committee
Yes

Publications

  • Vermorken JB, Peyrade F, Krauss J, Mesia R, Remenar E, Gauler TC, Keilholz U, Delord JP, Schafhausen P, Erfan J, Brummendorf TH, Iglesias L, Bethe U, Hicking C, Clement PM. Cisplatin, 5-fluorouracil, and cetuximab (PFE) with or without cilengitide in recurrent/metastatic squamous cell carcinoma of the head and neck: results of the randomized phase I/II ADVANTAGE trial (phase II part). Ann Oncol. 2014 Mar;25(3):682-688. doi: 10.1093/annonc/mdu003.

    PubMed 24567516

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Cilengitide 2000 mg once weekly, Cilengitide 2000 mg twice weekly and Cetuximab in people with Squamous Cell Cancer, run by Merck KGaA, Darmstadt, Germany at 37 sites in 9 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 3 inclusion and 5 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 30 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 37 sites in Germany, France, Belgium, Hungary, Italy and 4 more countries. 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?

Yes. Results are posted in the registry (first posted 30 Apr 2014). 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?

Progression-free Survival (PFS) Time: Investigator Read (time frame: Time from randomization to disease progression, death or last tumor assessment, reported between day of first participant randomized, 03 July 2009, until cut-off date (03 September 2011)). 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 NCT00705016, which also lists 1 linked publication.

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 30 Apr 2014.

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