Squamous Neck Carcinoma of the Head and Neck Cancer (SCCHN)Phase 2NCT00002774
Radiation Therapy and Combination Chemotherapy in Treating Patients With Stage III or Stage IV Head and Neck Cancer
A Phase 2 study testing Tirapazamine, Cisplatin and 5-fluorouracil in people with Squamous Neck Carcinoma of the Head and Neck Cancer (SCCHN), run by Stanford University at 2 sites in United States.
Trial summary
PURPOSE: Randomized phase 2 trial to compare the effectiveness of chemo-radiation therapy (RT + cisplatin + 5-FU) with or without tirapazamine for the treatment of patients with stage III or IV squamous cell carcinomas of the head and neck cancer (SCCHN). Read more about this study
- Who is it for?
- Ages 17 years and older
- Conditions the study is for
- Squamous Neck Carcinoma of the Head and Neck Cancer (SCCHN)
- What is being tested?
- Tirapazamine, Cisplatin and 5-fluorouracil
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 63 participants
- Where
- 2 sitesUnited States
- Study dates
- Jun 1996to Jun 2005
- Phase
- Phase 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 17 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
DISEASE CHARACTERISTICS:
Biopsy proven squamous cell carcinoma of the following head and neck sites:
Hypopharynx Oral cavity Larynx Oropharynx Nasal cavity Unknown primary Paranasal sinus
Histologically proven poorly-differentiated carcinoma of the following head and neck sites:
Hypopharynx Oral cavity Larynx Oropharynx Nasal cavity Paranasal sinus Stage III/IV (T0-4 N1-3 M0-2) disease
PATIENT CHARACTERISTICS:
WBC at least 3,000/mm3 Bilirubin no greater than 2.0 mg/dL AST no greater than 100 U/L Creatinine no greater than 2.0 mg/dL Creatinine clearance at least 60 mL/min (patients in Group N2-N3) No second malignancy within 5 years except curatively treated nonmelanomatous skin carcinoma No prior RT or chemotherapy, except prior radiotherapy to primary tumor allowed Not pregnant or nursing. Negative pregnancy test required Effective contraception required of fertile women Subjects with unknown primary cancers who had metastatic cervical lymph nodes are eligible Signed informed consent previously approved by the Institutional Review Board.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Veterans Affairs Medical Center - Palo Alto
Palo Alto, California, 94304
Stanford University Medical Center
Stanford, California, 94305-5408
About this study
Official title: Randomized Phase 2 Trial of Tirapazamine and the Role of Tumor Hypoxia in Advanced Squamous Head and Neck Cancer
PURPOSE: Randomized phase 2 trial to compare the effectiveness of chemo-radiation therapy (RT + cisplatin + 5-FU) with or without tirapazamine for the treatment of patients with stage III or IV squamous cell carcinomas of the head and neck cancer (SCCHN).
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. Radiation therapy uses high-energy x-rays to damage tumor cells.
Tirapazamine may increase the effectiveness of chemotherapy and radiation therapy by making tumor cells more sensitive to therapy.
Read the detailed description
Subjects were stratified according to pO2 values (high vs low), and randomized to 1 of 2 treatment arms, differing by the addition of tirapazamine to the therapeutic regimen. Treatment consists of two 21-day cycles of induction chemotherapy, followed by radiotherapy (RT).
Induction chemotherapy was cisplatin 100 mg/m2 per day administered over 4 hours on Study Days 1 and 22 (ie, 1st day of both induction cycles) with continuous infusion (CI) 5-FU at a dose of 1000 mg/m2 per day for 120 hours per cycle starting on Study Days 1 and 22 (ie, days 1 to 5 of both induction cycles).
Patients who achieve at least partial response proceeded to chemoradiotherapy (CRT) consisting of localized RT + cisplatin IV + 5-FU +/- tirapazamine. Location of RT was based on whether the site had a CR or PR. Radiotherapy began on day 43 (week 1), and continued for 5.5 weeks. Subjects with no response or progressive disease proceeded to salvage surgery.
A total of 63 patients were accrued for this study over approximately 5 years. 1 subject withdrew consent prior to treatment for personal reasons.
- Being tested
- Tirapazamine, Cisplatin, 5-fluorouracil, Radiotherapy (RT)
- Keywords
- stage III, stage IV, recurrent
- Medical subject headings
- Head and Neck Neoplasms, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TirapazamineDrug
Also called Tirazone, TPZ, SR 4233, 3-amino-1,4-benzotriazine-1-N-oxide
Tirapazamine is a benzotriazine with selective cytotoxicity for hypoxic cells. Under hypoxic conditions, it undergoes a 1-electron reduction to form a cytotoxic free radical that poisons topoisomerase II and causes DNA breaks, chromosomal aberrations, and cell death.
Tirapazamine was administered on Days 1 and 22 prior to the administration of neoadjuvant cisplatin and on Days 43, 45, 47, 71, 73, and 75 within 1 or 2 hours prior to each simultaneous cisplatin dose.
Tirapazamine dose was as follows:
Level 1 - 300 mg/m2 during the induction phase and 160 mg/m2 during the simultaneous phase (n = 4)
Level 2 - 330 mg/m2 during the induction phase and 260 mg/m2 during the simultaneous phase (n = 4)
Level 3 - 300 mg/m2 during the induction phase and 220 mg/m2 during the simultaneous phase (n = 25)
CisplatinDrug
Also called Cisplatinum, Cis-diamminedichloroplatinum(II), CDDP
The simultaneous chemoradiotherapy (CRT) regimen included cisplatin 20 mg/m2 administered 3 times per week.
5-fluorouracilDrug
Also called 5-FU
100 mg/m2 per day on Days 1 and 22, and continuous infusion (CI) 5-FU at a dose of 1000 mg/m2 per day for 120 hours per cycle starting on Days 1 and 22.
The simultaneous chemoradiotherapy (CRT) regimen included continuous infusion (CI) 5-FU 600 mg/m2 per day for 96 hours per cycle in Weeks 1 and 5 of RT.
Radiotherapy (RT)Radiation
During the CRT regimen, RT was given within 3 hrs of the tirapazamine infusion. The dose for the parallel opposed fields was 2 Gy/fraction/day given 5 dys/week up to a total dose of 66-70 Gy at the target lesion. The dose to the supraclavicular region was 50 Gy at a depth of 3 cm, delivered in 25 fractions. Supervoltage photons (≥4 megavolts) were used to treat both locations.
After 50 Gy were delivered to the primary site and regional lymph nodes, all sites were reassessed for clinical response by physical exam, direct fiber optic evaluation, and radiographic imaging (CT or MRI).
Subjects with a CR at both the primary site and the neck completed RT treatment to a total dose ≥66 Gy to the primary site and the involved lymph node(s). Subjects with a CR at the primary site but a partial response (PR) at the neck completed RT treatment to the primary site followed by neck dissection. Subjects with a PR at the primary site stopped radiation at 50 Gy and underwent salvage surgery.
| Study group | Role | What they receive |
|---|---|---|
| Tirapazamine + cisplatin + 5-FU | Experimental | 2 cycles of induction chemotherapy (tirapazamine, cisplatin, and 5-fluorouracil [5-FU]) followed by simultaneous chemoradiotherapy (tirapazamine, cisplatin, and 5-FU) Receives: Drug: Tirapazamine; Drug: Cisplatin; Drug: 5-fluorouracil; Radiation: Radiotherapy (RT) |
| Cisplatin + 5-FU | Active comparator | 2 cycles of induction chemotherapy (cisplatin + 5-fluorouracil [5-FU]) followed by simultaneous chemoradiotherapy (cisplatin + 5-FU) Receives: Drug: Cisplatin; Drug: 5-fluorouracil; Radiation: Radiotherapy (RT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete response rate (CRR)
Compare the CRR following CRT with or without tirapazamine in patients with squamous cell carcinoma of the head and neck.
Measured: 12 weeks
Secondary outcomes (3)
Overall survival (OS)
Survival was assessed at 5 years post-treatment.
Measured: 5 years
Cause-specific survival (CSS)
CSS is also known as disease-specific survival (DSS), and in this study represents cancer survival from diagnosis until death due to cancer, in the absence of other causes of death. All other causes of death are censored.
Measured: 5 years
Rate of freedom from recurrence (FFR)
FFR is the period until first treatment failure, and typically includes failure to achieve CR, but does not include deaths.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2004 (estimated)
- Study startJun 1996
- Primary completionJun 2000
- Study completionJun 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Squamous Neck Carcinoma of the Head and Neck Cancer (SCCHN)Studies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- 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
- Enrolment
- 63 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Harlan A. Pinto, MD, Study chair, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00002774
- Sponsor's protocol ID
- IRB-12503
- Other IDs
- CA67166, NCI-T94-0119O, CDR0000064752, SQL 72951
- Status last verified
- Jun 2014
- First submitted
- 6 Apr 2000
- Last updated
- 20 Jun 2014
- Results posted
- No
Publications
Le QT, Taira A, Budenz S, Jo Dorie M, Goffinet DR, Fee WE, Goode R, Bloch D, Koong A, Martin Brown J, Pinto HA. Mature results from a randomized Phase II trial of cisplatin plus 5-fluorouracil and radiotherapy with or without tirapazamine in patients with resectable Stage IV head and neck squamous cell carcinomas. Cancer. 2006 May 1;106(9):1940-9. doi: 10.1002/cncr.21785.
PubMed 16532436
Study at a glance
From the registry record, last updated by the sponsor on 20 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Phase 2 Trial of Tirapazamine and the Role of Tumor Hypoxia in Advanced Squamous Head and Neck Cancer
- ClinicalTrials.gov ID
- NCT00002774
- Acronym / sponsor ID
- IRB-12503
- Keywords
- stage III, stage IV, recurrent
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 63 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Jun 1996
- Primary completion
- Jun 2000 (actual)
- Study completion
- Jun 2005 (actual)
- First posted
- 6 Apr 2004 (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.
PURPOSE: Randomized phase 2 trial to compare the effectiveness of chemo-radiation therapy (RT + cisplatin + 5-FU) with or without tirapazamine for the treatment of patients with stage III or IV squamous cell carcinomas of the head and neck cancer (SCCHN).
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. Radiation therapy uses high-energy x-rays to damage tumor cells.
Tirapazamine may increase the effectiveness of chemotherapy and radiation therapy by making tumor cells more sensitive to therapy.
Detailed description
Subjects were stratified according to pO2 values (high vs low), and randomized to 1 of 2 treatment arms, differing by the addition of tirapazamine to the therapeutic regimen. Treatment consists of two 21-day cycles of induction chemotherapy, followed by radiotherapy (RT).
Induction chemotherapy was cisplatin 100 mg/m2 per day administered over 4 hours on Study Days 1 and 22 (ie, 1st day of both induction cycles) with continuous infusion (CI) 5-FU at a dose of 1000 mg/m2 per day for 120 hours per cycle starting on Study Days 1 and 22 (ie, days 1 to 5 of both induction cycles).
Patients who achieve at least partial response proceeded to chemoradiotherapy (CRT) consisting of localized RT + cisplatin IV + 5-FU +/- tirapazamine. Location of RT was based on whether the site had a CR or PR. Radiotherapy began on day 43 (week 1), and continued for 5.5 weeks. Subjects with no response or progressive disease proceeded to salvage surgery.
A total of 63 patients were accrued for this study over approximately 5 years. 1 subject withdrew consent prior to treatment for personal reasons.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tirapazamine + cisplatin + 5-FU | Experimental | Drug: Tirapazamine, Drug: Cisplatin, Drug: 5-fluorouracil, Radiation: Radiotherapy (RT)2 cycles of induction chemotherapy (tirapazamine, cisplatin, and 5-fluorouracil [5-FU]) followed by simultaneous chemoradiotherapy (tirapazamine, cisplatin, and 5-FU) |
| Cisplatin + 5-FU | Active comparator | Drug: Cisplatin, Drug: 5-fluorouracil, Radiation: Radiotherapy (RT)2 cycles of induction chemotherapy (cisplatin + 5-fluorouracil [5-FU]) followed by simultaneous chemoradiotherapy (cisplatin + 5-FU) |
Who may qualify
- Ages
- 17 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
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 |
|---|---|---|
| TirapazamineAlso: Tirazone, TPZ, SR 4233, 3-amino-1,4-benzotriazine-1-N-oxideTirapazamine is a benzotriazine with selective cytotoxicity for hypoxic cells. Under hypoxic conditions, it undergoes a 1-electron reduction to form a cytotoxic free radical that poisons topoisomerase II and causes DNA breaks, chromosomal aberrations, and cell death. Tirapazamine was administered on Days 1 and 22 prior to the administration of neoadjuvant cisplatin and on Days 43, 45, 47, 71, 73, and 75 within 1 or 2 hours prior to each simultaneous cisplatin dose. Tirapazamine dose was as follows: Level 1 - 300 mg/m2 during the induction phase and 160 mg/m2 during the simultaneous phase (n = 4) Level 2 - 330 mg/m2 during the induction phase and 260 mg/m2 during the simultaneous phase (n = 4) Level 3 - 300 mg/m2 during the induction phase and 220 mg/m2 during the simultaneous phase (n = 25) | Drug | Tirapazamine + cisplatin + 5-FU |
| CisplatinAlso: Cisplatinum, Cis-diamminedichloroplatinum(II), CDDPThe simultaneous chemoradiotherapy (CRT) regimen included cisplatin 20 mg/m2 administered 3 times per week. | Drug | Cisplatin + 5-FU, Tirapazamine + cisplatin + 5-FU |
| 5-fluorouracilAlso: 5-FU100 mg/m2 per day on Days 1 and 22, and continuous infusion (CI) 5-FU at a dose of 1000 mg/m2 per day for 120 hours per cycle starting on Days 1 and 22. The simultaneous chemoradiotherapy (CRT) regimen included continuous infusion (CI) 5-FU 600 mg/m2 per day for 96 hours per cycle in Weeks 1 and 5 of RT. | Drug | Cisplatin + 5-FU, Tirapazamine + cisplatin + 5-FU |
| Radiotherapy (RT)During the CRT regimen, RT was given within 3 hrs of the tirapazamine infusion. The dose for the parallel opposed fields was 2 Gy/fraction/day given 5 dys/week up to a total dose of 66-70 Gy at the target lesion. The dose to the supraclavicular region was 50 Gy at a depth of 3 cm, delivered in 25 fractions. Supervoltage photons (≥4 megavolts) were used to treat both locations. After 50 Gy were delivered to the primary site and regional lymph nodes, all sites were reassessed for clinical response by physical exam, direct fiber optic evaluation, and radiographic imaging (CT or MRI). Subjects with a CR at both the primary site and the neck completed RT treatment to a total dose ≥66 Gy to the primary site and the involved lymph node(s). Subjects with a CR at the primary site but a partial response (PR) at the neck completed RT treatment to the primary site followed by neck dissection. Subjects with a PR at the primary site stopped radiation at 50 Gy and underwent salvage surgery. | Radiation | Cisplatin + 5-FU, Tirapazamine + cisplatin + 5-FU |
Primary outcome
Complete response rate (CRR)
Time frame: 12 weeks
Compare the CRR following CRT with or without tirapazamine in patients with squamous cell carcinoma of the head and neck.
3 secondary outcomes
Overall survival (OS)
Time frame: 5 years
Cause-specific survival (CSS)
Time frame: 5 years
Rate of freedom from recurrence (FFR)
Time frame: 5 years
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 20 Jun 2014.
- Results publication: PubMed 16532436Le QT, Taira A, Budenz S, Jo Dorie M, Goffinet DR, Fee WE, Goode R, Bloch D, Koong A, Martin Brown J, Pinto HA. Mature results from a randomized Phase II trial of cisplatin plus 5-fluorouracil and radiotherapy with or without tirapazamine in patients with resectable Stage IV head and neck squamous cell carcinomas. Cancer. 2006 May 1;106(9):1940-9. doi: 10.1002/cncr.21785.
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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.
Harlan A. Pinto, MD study chair
Stanford University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tirapazamine, Cisplatin and 5-fluorouracil in people with Squamous Neck Carcinoma of the Head and Neck Cancer (SCCHN), run by Stanford University at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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 20 Jun 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. 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?
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?
Complete response rate (CRR) (time frame: 12 weeks). 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 NCT00002774, 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 20 Jun 2014.