Oropharynx CancerPhase 1/2NCT01108042
TPF-Induction Chemotherapy of Oropharyngeal and Cavity of the Mouth Cancer
A Phase 1/2 study testing Taxotere, Cisplatin, 5-Fluorouracil (5-FU) in people with Oropharynx Cancer and Squamous Cell Carcinoma of the Oral Cavity, run by Orlando Guntinas-Lichius, Prof. Dr. med. at 4 sites in Germany.
Trial summary
A combination therapy of Docetaxel, Cisplatin und 5-Fluorouracil (= TPF) will be used in patients with resectable oropharyngeal and cavity of the mouth cancer. To improve the compatibility of the TPF-induction without decreasing the efficacy the dose will be given on day 1 and 8 instead of applying the whole dose on… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Oropharynx Cancer, Squamous Cell Carcinoma of the Oral Cavity
- What is being tested?
- Taxotere, Cisplatin, 5-Fluorouracil (5-FU)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 71 participants
- Where
- 4 sitesGermany
- Study dates
- Nov 2009to Feb 2016
- 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 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histological proven, resectable squamous epithelial carcinoma of the oropharynx and the cavity of the mouth
- R0-resection possible
- All T N2 M0 / all T N3 M0 / if T3 or T4a also N0-1 M0
- Leucocytes > 4000/mm³ bzw. neutrophils > 2000/mm³, thrombocytes > 100000/mm³
- adequate kidney function, defined as serum creatinine und urea in normal range, Creatinine clearance > 60 ml/min
- adequate liver function with glutamate oxaloacetate transaminase (SGOT), glutamate pyruvate transaminase (SGPT) and bilirubin in normal range
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- electrolytes in normal range
- risks of anesthesia complications normal or minor increased
- Eastern Cooperative Oncology Group (ECOG) 0-2 / Karnofsky >= 60%
- Age 18 - 80 years
- signed written informed consent
- effective contraception for both male and female subjects if the risk of conception exists
Who cannot join
- T1 N0 M0 / T1 N1 M0 / T2 N0 M0 / T2 N1 M0
- Resection without curative intention: primary tumor is not treatable with resection methods
- Infiltration of the lower jaw
- M1 status
- Tumor not measurable with Innovation Center Computer Assisted Surgery (ICCAS) methods
- No prior chemotherapy or radiation (a primary surgery is allowed)
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- Metachronous or oder synchronous malignoma (Exception: basal cell carcinoma)
- Life expectance < 3 months
- ECOG > 2; Karnofsky < 60%
- acute infections or fever
- known HIV-infection or other immune suppression
- severe cardio pulmonary concomitant diseases
- chronic disease with continuous therapy (uncontrolled diabetes, rheumatoid arthritis) especially continuous therapy with steroids
- other concomitant diseases which, in the investigator's opinion, would exclude the patient from the study
- Contraindications which permit a therapy with Docetaxel, Cisplatin, 5-FU or radiation therapy
- missing patient's compliance
- regular Follow-up visits not possible
- Pregnancy or lactation period
- legal incapacity or limited legal capacity
- Participation in another clinical trial or administration of a not approved substance within 30 days before registration
Trial locations and contacts
4 sites in 1 country.
Germany4 sites
Städt. Kliniken Bielefeld gem. GmbH
Bielefeld, 33604
Friedrich-Schiller-University Jena
Jena, 07740
Universitätsklinikum Leipzig - Klinik und Poliklinik für HNO-Heilkunde
Leipzig, 04103
Klinikum Ernst von Bergmann
Potsdam, 14467
About this study
Official title: Phase I/II Study of Split-dose TPF-Induction Chemotherapy Before Surgery of Oropharyngeal and Cavity of the Mouth Cancer
A combination therapy of Docetaxel, Cisplatin und 5-Fluorouracil (= TPF) will be used in patients with resectable oropharyngeal and cavity of the mouth cancer. To improve the compatibility of the TPF-induction without decreasing the efficacy the dose will be given on day 1 and 8 instead of applying the whole dose on day 1 every 3 weeks.
In the phase I-part of the trial the optimal therapeutic dose of Docetaxel and Cisplatin will be defined.
In the phase II-part the progression-free survival after 2 years will be assessed in patients treated with the optimal therapeutic dose.
Read the detailed description
Local advanced Oropharyngeal and cavity of the mouth Cancer are often treated with a combination of surgery and/or radiation and /or chemotherapy.
Despite of therapy improvement there are only little advances in progression-free survival and overall survival.
Therefore new therapy concepts are needed. The advantage of the induction chemotherapy is the possibility of tumor response assessment during chemotherapy and may present a selection criterion for organ preservation.
In order to minimize the time between chemotherapy and surgery it is important to have an early answer for the tumor response. In this study response will be assessed after the first cycle of chemotherapy. Patients showing no tumor response will be operated at once. The other patients will receive further cycles of chemotherapy.
Toxicity of the induction chemotherapy have to be moderate because surgery should not be delayed.
To improve the tolerance of induction therapy the medication dose isn't given on day 1 every 3 weeks, but is dispersed on day 1 and day 8, q3weeks.
- Being tested
- Taxotere, Cisplatin, 5-Fluorouracil (5-FU)
- Medical subject headings
- Oropharyngeal Neoplasms, Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Taxotere, Cisplatin, 5-Fluorouracil (5-FU)Drug
Also called Docetaxel
Phase 1: Intravenous infusion of 40 mg/m² Taxotere and 40 mg/m² Cisplatin followed by 24 h-infusion of 2000 mg/m² 5-FU on day 1 and day 8 every 3 weeks. If possible an escalation to 50 mg/m² Taxotere and 50 mg/m² Cisplatin can be carried out. Phase 2: Optimal dose of phase 1 will be given.
| Study group | Role | What they receive |
|---|---|---|
| Taxotere, Cisplatin, 5-Fluorouracil (5-FU) | Experimental | Phase 1: Intravenous infusion of 40 mg/m² Taxotere and 40 mg/m² Cisplatin followed by 24 h-infusion of 2000 mg/m² 5-FU on day 1 and day 8 every 3 weeks. If possible an escalation to 50 mg/m² Taxotere and 50 mg/m² Cisplatin can be carried out. Receives: Drug: Taxotere, Cisplatin, 5-Fluorouracil (5-FU) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determination of progression-free survival after 2 years
Measured: 24 months
Secondary outcomes (5)
Overall survival after 2 years
Measured: after 2 years
Determination of the efficacy of the induction therapy
CT or magnetic resonance tomography (MRT) of the neck region
Measured: after 1, 12 and 24 months
Function of swallowing according the penetration-aspiration-scale
assessed according the penetration-aspiration-scale (PAS, Rosenbek et al. 1996) and according measuring after Prosiegel (Prosiegel et al. 2002).
Measured: 0,1, 6, 12, 18, 24 months
Adverse events as a measure of safety and tolerability
The number of patients with adverse events will be evaluated. Adverse events will be assessed according Common Terminology Criteria of Adverse Events (CTCAE) v.3.0 and analysed as number per patient and number per cycle.
Measured: once a week
Quality of life
European Organisation for Research and Treatment of Cancer (EORTC) Quality of life questionnaire (QLQ) for head and neck cancer patients (HN35) questionnaire filled in by the patients
Measured: 0,1, 6, 12, 18, 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2010 (estimated)
- Study startNov 2009
- Primary completionJan 2016
- Study completionFeb 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Oropharynx 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 71 participants (actual)
Sponsor and investigators
- Lead sponsor
- Orlando Guntinas-Lichius, Prof. Dr. med.
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Orlando Guntinas-Lichius, Prof. Dr. med., University of Jena
- Investigators
- Orlando Guntinas-Lichius, Prof. Dr., Principal investigator, Friedrich-Schiller-University Jena
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01108042
- Sponsor's protocol ID
- TISOC-1
- Other IDs
- 2009-011902-41, 2009
- Status last verified
- May 2016
- First submitted
- 14 Apr 2010
- Last updated
- 18 May 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Inhestern J, Schmalenberg H, Dietz A, Rotter N, Maschmeyer G, Jungehulsing M, Grosse-Thie C, Kuhnt T, Gorner M, Sudhoff H, Wittekindt C, Guntinas-Lichius O. A two-arm multicenter phase II trial of one cycle chemoselection split-dose docetaxel, cisplatin and 5-fluorouracil (TPF) induction chemotherapy before two cycles of split TPF followed by curative surgery combined with postoperative radiotherapy in patients with locally advanced oral and oropharyngeal squamous cell cancer (TISOC-1). Ann Oncol. 2017 Aug 1;28(8):1917-1922. doi: 10.1093/annonc/mdx202.
PubMed 28498880Inhestern J, Oertel K, Stemmann V, Schmalenberg H, Dietz A, Rotter N, Veit J, Gorner M, Sudhoff H, Junghanss C, Wittekindt C, Pachmann K, Guntinas-Lichius O. Prognostic Role of Circulating Tumor Cells during Induction Chemotherapy Followed by Curative Surgery Combined with Postoperative Radiotherapy in Patients with Locally Advanced Oral and Oropharyngeal Squamous Cell Cancer. PLoS One. 2015 Jul 17;10(7):e0132901. doi: 10.1371/journal.pone.0132901. eCollection 2015.
PubMed 26186556Oertel K, Spiegel K, Schmalenberg H, Dietz A, Maschmeyer G, Kuhnt T, Sudhoff H, Wendt TG, Guntinas-Lichius O. Phase I trial of split-dose induction docetaxel, cisplatin, and 5-fluorouracil (TPF) chemotherapy followed by curative surgery combined with postoperative radiotherapy in patients with locally advanced oral and oropharyngeal squamous cell cancer (TISOC-1). BMC Cancer. 2012 Oct 20;12:483. doi: 10.1186/1471-2407-12-483.
PubMed 23083061
Study at a glance
From the registry record, last updated by the sponsor on 18 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study of Split-dose TPF-Induction Chemotherapy Before Surgery of Oropharyngeal and Cavity of the Mouth Cancer
- ClinicalTrials.gov ID
- NCT01108042
- Acronym / sponsor ID
- TISOC-1
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 71 participants (actual)
- Lead sponsor
- Orlando Guntinas-Lichius, Prof. Dr. med.University, hospital or other
- Study start
- Nov 2009
- Primary completion
- Jan 2016 (actual)
- Study completion
- Feb 2016 (actual)
- First posted
- 21 Apr 2010 (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.
A combination therapy of Docetaxel, Cisplatin und 5-Fluorouracil (= TPF) will be used in patients with resectable oropharyngeal and cavity of the mouth cancer. To improve the compatibility of the TPF-induction without decreasing the efficacy the dose will be given on day 1 and 8 instead of applying the whole dose on day 1 every 3 weeks.
In the phase I-part of the trial the optimal therapeutic dose of Docetaxel and Cisplatin will be defined.
In the phase II-part the progression-free survival after 2 years will be assessed in patients treated with the optimal therapeutic dose.
Detailed description
Local advanced Oropharyngeal and cavity of the mouth Cancer are often treated with a combination of surgery and/or radiation and /or chemotherapy.
Despite of therapy improvement there are only little advances in progression-free survival and overall survival.
Therefore new therapy concepts are needed. The advantage of the induction chemotherapy is the possibility of tumor response assessment during chemotherapy and may present a selection criterion for organ preservation.
In order to minimize the time between chemotherapy and surgery it is important to have an early answer for the tumor response. In this study response will be assessed after the first cycle of chemotherapy. Patients showing no tumor response will be operated at once. The other patients will receive further cycles of chemotherapy.
Toxicity of the induction chemotherapy have to be moderate because surgery should not be delayed.
To improve the tolerance of induction therapy the medication dose isn't given on day 1 every 3 weeks, but is dispersed on day 1 and day 8, q3weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Taxotere, Cisplatin, 5-Fluorouracil (5-FU) | Experimental | Drug: Taxotere, Cisplatin, 5-Fluorouracil (5-FU)Phase 1: Intravenous infusion of 40 mg/m² Taxotere and 40 mg/m² Cisplatin followed by 24 h-infusion of 2000 mg/m² 5-FU on day 1 and day 8 every 3 weeks. If possible an escalation to 50 mg/m² Taxotere and 50 mg/m² Cisplatin can be carried out. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Histological proven, resectable squamous epithelial carcinoma of the oropharynx and the cavity of the mouth
- R0-resection possible
- All T N2 M0 / all T N3 M0 / if T3 or T4a also N0-1 M0
- Leucocytes > 4000/mm³ bzw. neutrophils > 2000/mm³, thrombocytes > 100000/mm³
- adequate kidney function, defined as serum creatinine und urea in normal range, Creatinine clearance > 60 ml/min
Key exclusion criteria (20 listed)
- T1 N0 M0 / T1 N1 M0 / T2 N0 M0 / T2 N1 M0
- Resection without curative intention: primary tumor is not treatable with resection methods
- Infiltration of the lower jaw
- M1 status
- Tumor not measurable with Innovation Center Computer Assisted Surgery (ICCAS) methods
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 |
|---|---|---|
| Taxotere, Cisplatin, 5-Fluorouracil (5-FU)Also: DocetaxelPhase 1: Intravenous infusion of 40 mg/m² Taxotere and 40 mg/m² Cisplatin followed by 24 h-infusion of 2000 mg/m² 5-FU on day 1 and day 8 every 3 weeks. If possible an escalation to 50 mg/m² Taxotere and 50 mg/m² Cisplatin can be carried out. Phase 2: Optimal dose of phase 1 will be given. | Drug | Taxotere, Cisplatin, 5-Fluorouracil (5-FU) |
Primary outcome
Determination of progression-free survival after 2 years
Time frame: 24 months
5 secondary outcomes
Overall survival after 2 years
Time frame: after 2 years
Determination of the efficacy of the induction therapy
Time frame: after 1, 12 and 24 months
Function of swallowing according the penetration-aspiration-scale
Time frame: 0,1, 6, 12, 18, 24 months
Adverse events as a measure of safety and tolerability
Time frame: once a week
Quality of life
Time frame: 0,1, 6, 12, 18, 24 months
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 18 May 2016.
- Derived from this study: PubMed 28498880Inhestern J, Schmalenberg H, Dietz A, Rotter N, Maschmeyer G, Jungehulsing M, Grosse-Thie C, Kuhnt T, Gorner M, Sudhoff H, Wittekindt C, Guntinas-Lichius O. A two-arm multicenter phase II trial of one cycle chemoselection split-dose docetaxel, cisplatin and 5-fluorouracil (TPF) induction chemotherapy before two cycles of split TPF followed by curative surgery combined with postoperative radiotherapy in patients with locally advanced oral and oropharyngeal squamous cell cancer (TISOC-1). Ann Oncol. 2017 Aug 1;28(8):1917-1922. doi: 10.1093/annonc/mdx202.
- Derived from this study: PubMed 26186556Inhestern J, Oertel K, Stemmann V, Schmalenberg H, Dietz A, Rotter N, Veit J, Gorner M, Sudhoff H, Junghanss C, Wittekindt C, Pachmann K, Guntinas-Lichius O. Prognostic Role of Circulating Tumor Cells during Induction Chemotherapy Followed by Curative Surgery Combined with Postoperative Radiotherapy in Patients with Locally Advanced Oral and Oropharyngeal Squamous Cell Cancer. PLoS One. 2015 Jul 17;10(7):e0132901. doi: 10.1371/journal.pone.0132901. eCollection 2015.
- Derived from this study: PubMed 23083061Oertel K, Spiegel K, Schmalenberg H, Dietz A, Maschmeyer G, Kuhnt T, Sudhoff H, Wendt TG, Guntinas-Lichius O. Phase I trial of split-dose induction docetaxel, cisplatin, and 5-fluorouracil (TPF) chemotherapy followed by curative surgery combined with postoperative radiotherapy in patients with locally advanced oral and oropharyngeal squamous cell cancer (TISOC-1). BMC Cancer. 2012 Oct 20;12:483. doi: 10.1186/1471-2407-12-483.
- Individual participant dataSharing planned: No
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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.
Orlando Guntinas-Lichius, Prof. Dr. principal investigator
Friedrich-Schiller-University Jena
4 sites 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 Taxotere, Cisplatin, 5-Fluorouracil (5-FU) in people with Oropharynx Cancer and Squamous Cell Carcinoma of the Oral Cavity, run by Orlando Guntinas-Lichius, Prof. Dr. med. at 4 sites in Germany.
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 20 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 18 May 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Germany. 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?
Determination of progression-free survival after 2 years (time frame: 24 months). 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 NCT01108042, which also lists 3 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 18 May 2016.