Squamous Cell Carcinoma of the Head and NeckPhase 1HNSCCNCT01716416
Pazopanib Plus Cetuximab for Incurable Head and Neck Squamous Cell Carcinoma (HNSCC)
A Phase 1 study testing Pazopanib and Cetuximab in people with Squamous Cell Carcinoma of the Head and Neck, run by Washington University School of Medicine at 1 site in United States.
Trial summary
This phase I trial studies the side effects and best dose of pazopanib hydrochloride (pazopanib) when given together with cetuximab in treating patients with incurable recurrent or metastatic head and neck cancer. Pazopanib may stop the growth of cancer by blocking blood flow to the tumor. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Squamous Cell Carcinoma of the Head and Neck
- What is being tested?
- Pazopanib and Cetuximab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- 31 May 2013to 31 Aug 2017
- Phase
- Phase 1
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient must have histologically confirmed diagnosis of incurable metastatic or recurrent head and neck squamous cell carcinoma
- Patient must have measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥10 mm with CT scan, as ≥20 mm by chest x-ray, or ≥10 mm with calipers by clinical exam (Expanded Cohort only; patients without measurable disease by RECIST 1.1 criteria but with evaluable disease will be eligible for the dose-finding phase).
- Patient must be ≥ 18 years of age.
- Patient must have an ECOG performance status 0-1
- Patient must have normal bone marrow and organ function as defined below:
- Absolute neutrophil count ≥ 1,500/mcL
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- Platelets ≥ 100,000/mcL
- Hemoglobin ≥ 9.0 g/dL
- INR ≤ 1.2 x IULN; patients receiving anticoagulant therapy are eligible if their INR is stable and within the recommended range for the desired level of anticoagulation
- aPTT ≤ 1.2 x IULN
- Corrected QT interval (QTc) < 480 msecs
- Total bilirubin ≤ 1.5 x IULN
- AST(SGOT) ≤ 2.5 x IULN and ALT(SGPT) ≤ 2.5 x IULN
- Creatinine ≤ 1.5 mg/dL OR Creatinine clearance ≥ 50 mL/min/1.73 m2 for patients with creatinine levels > 1.5 mg/dL
- Urine protein to creatinine ratio (UPC) < 1; if UPC ≥ 1, then a 24-hour urine protein must be assessed; patients must have a 24-hour urine protein value < 1 g to be eligible
- Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) beginning 14 days prior to first dose of pazopanib, through the dosing period, and for at least 28 days after the last dose of pazopanib.
- Patient must be able to understand and willing to sign an IRB approved written informed consent document.
Who cannot join
- For the expanded cohort only, patient must not have had prior therapy with an EGFR-specific monoclonal antibody or EGFR-specific TKI for treatment of incurable HNSCC. Prior therapy with an EGFR-specific monoclonal antibody as part of the definitive treatment of curable HNSCC is acceptable if this occurred more than 3 months prior to study enrollment. For the dose-finding cohorts, prior EGFR-specific therapy in the incurable setting is allowed.
- Patient must not have had radiation therapy, minor surgery, or tumor embolization with 14 days prior to the first dose of pazopanib.
- Patient must not have had chemotherapy, immunotherapy, biologic therapy, hormonal therapy, or investigational therapy within 14 days or 5 half-lives of the drug prior to the first dose of pazopanib. For patients enrolling in the phase I portion of this study, this requirement does not apply to prior treatment with cetuximab.
- Patient must not have prior major surgery, trauma, presence of any non-healing wound, fracture, or ulcer within 28 days prior to first dose of study drug.
- Patient must not have a history of other malignancy ≤ 2 years previous with the exception of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma.
- Patient must not be receiving any medication that is a strong CYP3A4 inhibitor beginning 14 days prior to first dose of study drug. Strong CYP3A4 inhibitors include (but are not limited to): antibiotics such as clarithromycin, telithromycin, troleandromycin; protease inhibitors such as ritonavir, indinavir, saquinavir, nelfinavir, lopinavir; antifungals such as itraconazole, ketoconazole, voriconazole; and antidepressants such as nefazodone.
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- Patient must not be receiving any other investigational agents.
- Patient must not be experiencing any ongoing toxicity from prior anti-cancer therapy that is > grade 1 or that is progressing in severity, except alopecia.
- Patient must not have a history of or clinical evidence of central nervous system metastases or leptomeningeal carcinomatosis, except for individuals who have had previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medications for 6 months prior to first dose of pazopanib.
- Patient must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to pazopanib, cetuximab, or other agents used in the study.
- Patient must not have any clinically significant gastrointestinal abnormality that may increase the risk of GI bleeding including, but not limited to, active peptic ulcer disease, known intraluminal metastatic lesions with risk of bleeding, inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease), other GI conditions with increased risk of perforation, history of abdominal fistula or GI perforation or intra-abdominal abscess within 28 days prior to beginning study treatment.
- Patient must not have any clinically significant abnormality that may affect absorption of investigational product including, but not limited to, malabsorption syndrome or major resection of the stomach or small bowel.
- Patient must not have an uncontrolled intercurrent illness within the 6 months prior to study entry including, but not limited to, ongoing or active infection, Class III or IV congestive heart failure (as defined by the New York Heart Association (NYHA)), unstable angina pectoris, cardiac arrhythmia, myocardial infarction, cardiac angioplasty or stenting, coronary artery bypass graft surgery, symptomatic peripheral vascular disease, or psychiatric illness/social situations that would limit compliance with study requirements.
- Patient must not have poorly controlled hypertension (defined as systolic blood pressure of ≥ 140 mmHg or diastolic blood pressure of ≥ 90 mmHg). Initiation or adjustment of antihypertensive medications is permitted prior to study entry. Blood pressure must be re-assessed on two occasions that are separated by a minimum of one hour; on each of these occasions, the mean (of 3 readings) from each assessment must be < 140/90 mmHg for a patient to be eligible for this study.
- Patient must not have a history of cerebrovascular accident including transient ischemic attack within the past 6 months. Patients with recent deep venous thrombosis or pulmonary embolism who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible as long as INR is stable.
- Patient must not have evidence of active bleeding or bleeding diathesis.
- Patient must not have any known endobronchial lesions and/or lesions infiltrating major pulmonary vessels.
- Patient must not experience hemoptysis in excess of 2.5 mL within 8 weeks prior to the first dose of pazopanib.
- Patient must not be pregnant and/or breastfeeding. Patient must have a negative serum pregnancy test within 14 days of study entry.
- Patient must not be known to be HIV-positive on combination antiretroviral because of the potential for pharmacokinetic interactions with pazopanib. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: A Phase I Trial of Pazopanib Suspension Plus Cetuximab in Patients With Incurable Head and Neck Squamous Cell Carcinoma
This phase I trial studies the side effects and best dose of pazopanib hydrochloride (pazopanib) when given together with cetuximab in treating patients with incurable recurrent or metastatic head and neck cancer. Pazopanib may stop the growth of cancer by blocking blood flow to the tumor. Pazopanib may also block some of the enzymes needed for cell growth. Cetuximab is a monoclonal antibody that blocks the ability of some tumor cells to grow and spread. Giving pazopanib with cetuximab may provide a more effective treatment for patients with advanced head and neck cancer.
- Being tested
- Pazopanib, Cetuximab
- Medical subject headings
- 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.
PazopanibDrug
Also called Votrient®
CetuximabDrug
Also called Erbitux®
| Study group | Role | What they receive |
|---|---|---|
| Dose Level 1 | Experimental | Pazopanib 200 mg PO QD
Cetuximab 400 mg/m^2 (cycle 1 week 1 only) followed by weekly maintenance doses of 250 mg/m^2 Receives: Drug: Pazopanib; Drug: Cetuximab |
| Dose Level 2 | Experimental | Pazopanib 400 mg PO QD
Cetuximab 400 mg/m^2 (cycle 1 week 1 only) followed by weekly maintenance doses of 250 mg/m^2 Receives: Drug: Pazopanib; Drug: Cetuximab |
| Dose Level 3 | Experimental | Pazopanib 600 mg PO QD
Cetuximab 400 mg/m^2 (cycle 1 week 1 only) followed by weekly maintenance doses of 250 mg/m^2 Receives: Drug: Pazopanib; Drug: Cetuximab |
| Dose Level 4 | Experimental | Pazopanib 800 mg PO QD
Cetuximab 400 mg/m^2 (cycle 1 week 1 only) followed by weekly maintenance doses of 250 mg/m^2 Receives: Drug: Pazopanib; Drug: Cetuximab |
| Part 2 Dose | Experimental | Pazopanib (dose to be determined in Part 1 of study) mg PO QD
Cetuximab 400 mg/m^2 (cycle 1 week 1 only) followed by weekly maintenance doses of 250 mg/m^2 Receives: Drug: Pazopanib; Drug: Cetuximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerable dose (MTD) of pazopanib suspension when combined with fixed dose cetuximab in patients with incurable HNSCC.
Measured: 9 weeks (completion of all patients in part 1 of study through 1st cycle)
Secondary outcomes (7)
Early Adverse events
Graded by NCI-CTC criteria version 4 and described in a frequency distribution analysis for the first 8 weeks of pazopanib and cetuximab
Measured: 8 weeks
Late adverse events
Graded by NCI-CTC criteria version 4 and described in a frequency distribution analysis for subsequent interval (after first 8 weeks of therapy) of receiving pazopanib and cetuximab
Measured: Weeks 8 through 16
Anatomic tumor response
Assessed by CT and clinical exam
Measured: 8 weeks
Overall metabolic response
Assessed by FDG-PET
Measured: 8 weeks
Overall response rate
CR+PR
Measured: 8 weeks
Duration of overall response
Time from CR or PR until relapse
Measured: 8 weeks
Best overall response rates in patients treated with MTD
According to RECIST criteria
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2012 (estimated)
- Study start31 May 2013
- Primary completion31 Jul 2015
- Study completion31 Aug 2017
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 Cell Carcinoma of the Head and NeckStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Douglas Adkins, M.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01716416
- Sponsor's protocol ID
- 201211110
- Acronym
- HNSCC
- Status last verified
- Apr 2019
- First submitted
- 24 Oct 2012
- Last updated
- 16 Apr 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Adkins D, Mehan P, Ley J, Siegel MJ, Siegel BA, Dehdashti F, Jiang X, Salama NN, Trinkaus K, Oppelt P. Pazopanib plus cetuximab in recurrent or metastatic head and neck squamous cell carcinoma: an open-label, phase 1b and expansion study. Lancet Oncol. 2018 Aug;19(8):1082-1093. doi: 10.1016/S1470-2045(18)30350-4. Epub 2018 Jul 11.
PubMed 30001987
Study at a glance
From the registry record, last updated by the sponsor on 16 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial of Pazopanib Suspension Plus Cetuximab in Patients With Incurable Head and Neck Squamous Cell Carcinoma
- ClinicalTrials.gov ID
- NCT01716416
- Acronym / sponsor ID
- HNSCC / 201211110
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Study start
- 31 May 2013 (actual)
- Primary completion
- 31 Jul 2015 (actual)
- Study completion
- 31 Aug 2017 (actual)
- First posted
- 29 Oct 2012 (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.
This phase I trial studies the side effects and best dose of pazopanib hydrochloride (pazopanib) when given together with cetuximab in treating patients with incurable recurrent or metastatic head and neck cancer. Pazopanib may stop the growth of cancer by blocking blood flow to the tumor. Pazopanib may also block some of the enzymes needed for cell growth. Cetuximab is a monoclonal antibody that blocks the ability of some tumor cells to grow and spread. Giving pazopanib with cetuximab may provide a more effective treatment for patients with advanced head and neck cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Dose Level 1 | Experimental | Drug: Pazopanib, Drug: CetuximabPazopanib 200 mg PO QD Cetuximab 400 mg/m^2 (cycle 1 week 1 only) followed by weekly maintenance doses of 250 mg/m^2 |
| Dose Level 2 | Experimental | Drug: Pazopanib, Drug: CetuximabPazopanib 400 mg PO QD Cetuximab 400 mg/m^2 (cycle 1 week 1 only) followed by weekly maintenance doses of 250 mg/m^2 |
| Dose Level 3 | Experimental | Drug: Pazopanib, Drug: CetuximabPazopanib 600 mg PO QD Cetuximab 400 mg/m^2 (cycle 1 week 1 only) followed by weekly maintenance doses of 250 mg/m^2 |
| Dose Level 4 | Experimental | Drug: Pazopanib, Drug: CetuximabPazopanib 800 mg PO QD Cetuximab 400 mg/m^2 (cycle 1 week 1 only) followed by weekly maintenance doses of 250 mg/m^2 |
| Part 2 Dose | Experimental | Drug: Pazopanib, Drug: CetuximabPazopanib (dose to be determined in Part 1 of study) mg PO QD Cetuximab 400 mg/m^2 (cycle 1 week 1 only) followed by weekly maintenance doses of 250 mg/m^2 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Patient must have histologically confirmed diagnosis of incurable metastatic or recurrent head and neck squamous cell carcinoma
- Patient must have measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥10 mm with CT scan, as ≥20 mm by chest x-ray, or ≥10 mm with calipers by clinical exam (Expanded Cohort only; patients without measurable disease by RECIST 1.1 criteria but with evaluable disease will be eligible for the dose-finding phase).
- Patient must be ≥ 18 years of age.
- Patient must have an ECOG performance status 0-1
- Patient must have normal bone marrow and organ function as defined below:
Key exclusion criteria (20 listed)
- For the expanded cohort only, patient must not have had prior therapy with an EGFR-specific monoclonal antibody or EGFR-specific TKI for treatment of incurable HNSCC. Prior therapy with an EGFR-specific monoclonal antibody as part of the definitive treatment of curable HNSCC is acceptable if this occurred more than 3 months prior to study enrollment. For the dose-finding cohorts, prior EGFR-specific therapy in the incurable setting is allowed.
- Patient must not have had radiation therapy, minor surgery, or tumor embolization with 14 days prior to the first dose of pazopanib.
- Patient must not have had chemotherapy, immunotherapy, biologic therapy, hormonal therapy, or investigational therapy within 14 days or 5 half-lives of the drug prior to the first dose of pazopanib. For patients enrolling in the phase I portion of this study, this requirement does not apply to prior treatment with cetuximab.
- Patient must not have prior major surgery, trauma, presence of any non-healing wound, fracture, or ulcer within 28 days prior to first dose of study drug.
- Patient must not have a history of other malignancy ≤ 2 years previous with the exception of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma.
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 |
|---|---|---|
| PazopanibAlso: Votrient® | Drug | Dose Level 1, Dose Level 2, Dose Level 3, Dose Level 4, Part 2 Dose |
| CetuximabAlso: Erbitux® | Drug | Dose Level 1, Dose Level 2, Dose Level 3, Dose Level 4, Part 2 Dose |
Primary outcome
Maximum tolerable dose (MTD) of pazopanib suspension when combined with fixed dose cetuximab in patients with incurable HNSCC.
Time frame: 9 weeks (completion of all patients in part 1 of study through 1st cycle)
7 secondary outcomes
Early Adverse events
Time frame: 8 weeks
Late adverse events
Time frame: Weeks 8 through 16
Anatomic tumor response
Time frame: 8 weeks
Overall metabolic response
Time frame: 8 weeks
Overall response rate
Time frame: 8 weeks
Duration of overall response
Time frame: 8 weeks
Best overall response rates in patients treated with MTD
Time frame: 8 weeks
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 16 Apr 2019.
- Derived from this study: PubMed 30001987Adkins D, Mehan P, Ley J, Siegel MJ, Siegel BA, Dehdashti F, Jiang X, Salama NN, Trinkaus K, Oppelt P. Pazopanib plus cetuximab in recurrent or metastatic head and neck squamous cell carcinoma: an open-label, phase 1b and expansion study. Lancet Oncol. 2018 Aug;19(8):1082-1093. doi: 10.1016/S1470-2045(18)30350-4. Epub 2018 Jul 11.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
- 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.
Douglas Adkins, M.D. principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Pazopanib and Cetuximab in people with Squamous Cell Carcinoma of the Head and Neck, run by Washington University School of Medicine at 1 site 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?
The sponsor lists 17 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 16 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 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.
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?
Maximum tolerable dose (MTD) of pazopanib suspension when combined with fixed dose cetuximab in patients with incurable HNSCC. (time frame: 9 weeks (completion of all patients in part 1 of study through 1st cycle)). 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 NCT01716416, 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 16 Apr 2019.