Squamous Cell Carcinoma of the Head and NeckPhase 2NCT01051791
Phase II Study of RAD001 Head and Neck Cancer
A Phase 2 study testing Everolimus 10mg daily in people with Squamous Cell Carcinoma of the Head and Neck, run by Julie E. Bauman, MD, MPH at 1 site in United States.
Trial summary
To carry out exploratory studies to determine if activity of this regimen correlates with tumor and patient associated markers of the EGF-R/mTOR pathway These markers may correlate with activity of this regimen and provide exploratory insights in to the mechanism of this treatment approach. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Squamous Cell Carcinoma of the Head and Neck
- What is being tested?
- Everolimus 10mg daily
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2010to 5 Aug 2016
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically or cytologically documented squamous cell CA of the head and neck
- Metastatic and/or recurrent head and neck cancer (not eligible for curative intent surgical or radiation therapy)
- Patients must have at least one measurable site of disease according to RECIST criteria that has not been previously irradiated. If the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation
- Performance status 0-2
- Age ≥18 years
- Non-pregnant
Show all 15Show fewer
- Prior treatment:
- Prior treatment for recurrent or metastatic disease required (at least one): up to but no more than 2 regimens (chemotherapy and/or biologic) allowed.
- Prior induction and concomitant chemoradiotherapy with a curative intent (with or without biologic agents) is allowed
- No other serious medical or psychiatric disease
- Required Lab Values:
- Granulocytes ≥ 1,500/µl Platelets ≥ 100,000/µl Bilirubin ≤ 1.5 x ULN INR ≥ 1.3 (or < 3 if on anticoagulation) AST or ALT ≤ 2.5 x ULN (< 5 x ULN in patients with liver metastases) Creatinine ≤ ULN or Creatinine Clearance >= 60 mL/min, if creatinine above ULN
- Fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L AND fasting triglycerides ≤ 2.5 x ULN. NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication.
- Patients with accessible tumor tissue must agree to a pre-treatment biopsy at screening. If available, original diagnostic tissue may be submitted in place of the pre-treatment biopsy.
- Signed informed consent
Who cannot join
- Patients currently receiving anticancer therapies or who have received anticancer therapies within 4 weeks of the start of study drug (including chemotherapy, radiation therapy, antibody based therapy, etc.)
- Patients, who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or patients that may require major surgery during the course of the study
- Prior treatment with any investigational drug within the preceding 4 weeks
- Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent, except corticosteroids with a daily dosage equivalent to prednisone ≤ 20 mg. However, patients receiving corticosteroids must have been on a stable dosage regimen for a minimum of 4 weeks prior to the first treatment with RAD001. Topical or inhaled corticosteroids are allowed.
- Patients should not receive immunization with attenuated live vaccines within one week of study entry or during study period
- Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases
Show all 21Show fewer
- Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin.
- Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
- Symptomatic congestive heart failure of New York heart Association Class III or IV
- unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease
- severely impaired lung function as defined as spirometry and DLCO that is 50% of the normal predicted value and/or 02 saturation that is 88% or less at rest on room air. PFTs as clinically indicated.
- uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN
- active (acute or chronic) or uncontrolled severe infections
- liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis
- A known history of HIV seropositivity
- Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
- Patients with an active, bleeding diathesis
- Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. If barrier contraceptives are being used, these must be continued throughout the trial by both sexes. Hormonal contraceptives are not acceptable as a sole method of contraception. (Women of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to administration of RAD001)
- Patients who have received prior treatment with an mTOR inhibitor (sirolimus, temsirolimus, everolimus).
- Patients with a known hypersensitivity to RAD001 (everolimus) or other rapamycins (sirolimus, temsirolimus) or to its excipients
- Patients unwilling to or unable to comply with the protocol
Trial locations and contacts
1 site in 1 country.
United States1 site
Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
About this study
Official title: Phase II Study of RAD001 for Treatment of Refractory, Recurrent, Locally Advanced Squamous Cell Carcinoma of the Head and Neck
To carry out exploratory studies to determine if activity of this regimen correlates with tumor and patient associated markers of the EGF-R/mTOR pathway These markers may correlate with activity of this regimen and provide exploratory insights in to the mechanism of this treatment approach.
Expression of the pathway components including EGF-R and phosphorylated EGF-R (p-EGF-R), ERK and p-ERK, Akt and p-Akt(T308 and S473), p70s6k and p-p70s6k, S6 and p-S6, HIF-1-alpha, p27 and 4E-BP1 will be assessed. Mutation and FISH analysis for EGF-R expression will also be performed on tumor samples. Biopsies will be obtained at the following times: pre-treatment, and after 4 weeks (one cycle) of treatment. If available, original diagnostic tissue may be submitted in place of the pre-treatment biopsy.
Read the detailed description
The study of the efficacy of RAD001 will proceed in two stages after the method of Simon . In the first stage 15 patients will be accrued and treated. If 9 or fewer patients show clinical benefit the study will be terminated. If 10 or more patients show clinical benefit the study will proceed to the second stage, accruing an additional 26 patients. If the second stage is complete and a total of 29 or more patients show clinical benefit among the 41 patients treated, the treatment CBR for will be considered high enough to warrant further study. Conversely, if the evaluation of RAD001 concludes at the first stage, or if 28 or fewer patients experience a clinical benefit after completing the second stage, the therapy will not be considered for further study.
Current knowledge about the molecular mechanisms of cancer-related pathways involved in cellular signaling, cell cycle regulation and cell death is yielding therapies directed at specific components of these pathways, such as the epidermal growth factor receptor (EGF-R), the mammalian target of rapamycin (mTOR), the vascular endothelial growth factor receptor (VEGF-R) and the insulin-like growth factor receptor (IFG-R). Both small molecule and monoclonal antibody therapies directed against these targets are available. Furthermore, immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) and mutation analysis are available for profiling expression of pathway components, raising the possibility of individualized prognosis and therapy.
One receptor in particular, is both a prognostic factor and a therapeutic target in HNSCC. Upregulation of EGF-R expression and aberrant activation of kinase cascades downstream of this receptor occur early in the process of carcinogenesis and play a major role in malignant progression.1 The level of EGF-R expression correlates with recurrence and poor prognosis in HNSCC. A well tolerated anti-EGF-R monoclonal antibody, cetuximab, has shown remarkable activity against HNSCC, including statistically significant improvement in survival for patients with locally advanced disease treated with radiotherapy, leading to its regulatory approval for this disease.2 Unfortunately, despite survival advances achieved with EGF-R inhibitors, the majority (~60%) of patients with advanced disease are refractory to EGF-R directed therapies.3 One anticipated mechanism by which the current regimen may fail in some patients is the upregulation of escape pathways downstream of the EGF-R. A pathway of particular interest is the PI3/AKT/mTOR axis, within which the mTOR protein may be targeted by the tyrosine kinase inhibitor RAD001.
In order to investigate pathway components that may act as an escape mechanism while concurrently targeting a downstream kinase that may enable rescue from resistance to EGF-R directed therapies, we propose this prospective, phase II, single-arm, single-agent interventional clinical trial of RAD001 for patients with refractory SCCHN. The primary outcome is activity of RAD001 while secondary outcomes include safety, toxicity and extensive laboratory correlates to be performed on tumor tissues. By carrying out this clinic-translational trial of the novel mTOR inhibitor, RAD001, in patients with refractory SCCHN, we aim to explore mechanisms of activity of and resistance to inhibitors of the EGF-R pathway components while measuring the clinical activity of RAD001.
- Being tested
- Everolimus 10mg daily
- Keywords
- RAD001, Everolimus
- 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.
Everolimus 10mg dailyDrug
Also called Everolimus
RAD001 is a pill that will be taken orally (by mouth), at a dose of 10 mg, once a day for 28 days.
| Study group | Role | What they receive |
|---|---|---|
| Everolimus 10 mg daily | Experimental | The study of the efficacy of everolimus will proceed in two stages after the method of Simon1. In the first stage 15 patients will be accrued and treated. If 9 or fewer patients show clinical benefit the study will be terminated. If 10 or more patients show clinical benefit the study will proceed to the second stage, accruing an additional 26 patients. If the second stage is complete and a total of 29 or more patients show clinical benefit among the 41 patients treated, the treatment CBR for will be considered high enough to warrant further study. Conversely, if the evaluation of everolimus concludes at the first stage, or if 28 or fewer patients experience a clinical benefit after completing the second stage, the therapy will not be considered for further study.
1 Receives: Drug: Everolimus 10mg daily |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Benefit Rate (CBR)
The number of patients with recurrent/refractory SCCHN (head and neck squamous cell carcinoma) treated with single-agent everolimus that, experience a Complete Response (CR) + number of patients that experience a Partial Response (PR ) + number of patients that experience Stable Disease (SD) / total evaluable patients.
Measured: Up to 60 months
Secondary outcomes (3)
Progression Free Survival (PFS)
Measured: Up to 60 months
Overall Survival (OS)
Measured: Up to 60 months
Objective Response Rate (ORR)
The number of patients with recurrent/refractory SCCHN (head and neck squamous cell carcinoma) treated with single-agent everolimus that, experience a Complete Response (CR) + number of patients that experience a Partial Response (PR ) / total evaluable patients.
Measured: Up to 60 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jan 2010 (estimated)
- Study startJan 2010
- Primary completion26 Apr 2011
- Study completion5 Aug 2016
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.
- Other trials for Squamous Cell Carcinoma of the Head and NeckStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Julie E. Bauman, MD, MPH
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Sponsor-investigator, Julie E. Bauman, MD, MPH, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01051791
- Sponsor's protocol ID
- 08-032
- Status last verified
- Nov 2017
- First submitted
- 18 Jan 2010
- Last updated
- 19 Dec 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of RAD001 for Treatment of Refractory, Recurrent, Locally Advanced Squamous Cell Carcinoma of the Head and Neck
- ClinicalTrials.gov ID
- NCT01051791
- Acronym / sponsor ID
- 08-032
- Keywords
- RAD001, Everolimus
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Julie E. Bauman, MD, MPHUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- Jan 2010
- Primary completion
- 26 Apr 2011 (actual)
- Study completion
- 5 Aug 2016 (actual)
- First posted
- 20 Jan 2010 (estimated)
- Results
- Posted 19 Dec 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To carry out exploratory studies to determine if activity of this regimen correlates with tumor and patient associated markers of the EGF-R/mTOR pathway These markers may correlate with activity of this regimen and provide exploratory insights in to the mechanism of this treatment approach.
Expression of the pathway components including EGF-R and phosphorylated EGF-R (p-EGF-R), ERK and p-ERK, Akt and p-Akt(T308 and S473), p70s6k and p-p70s6k, S6 and p-S6, HIF-1-alpha, p27 and 4E-BP1 will be assessed. Mutation and FISH analysis for EGF-R expression will also be performed on tumor samples. Biopsies will be obtained at the following times: pre-treatment, and after 4 weeks (one cycle) of treatment. If available, original diagnostic tissue may be submitted in place of the pre-treatment biopsy.
Detailed description
The study of the efficacy of RAD001 will proceed in two stages after the method of Simon . In the first stage 15 patients will be accrued and treated. If 9 or fewer patients show clinical benefit the study will be terminated. If 10 or more patients show clinical benefit the study will proceed to the second stage, accruing an additional 26 patients. If the second stage is complete and a total of 29 or more patients show clinical benefit among the 41 patients treated, the treatment CBR for will be considered high enough to warrant further study. Conversely, if the evaluation of RAD001 concludes at the first stage, or if 28 or fewer patients experience a clinical benefit after completing the second stage, the therapy will not be considered for further study.
Current knowledge about the molecular mechanisms of cancer-related pathways involved in cellular signaling, cell cycle regulation and cell death is yielding therapies directed at specific components of these pathways, such as the epidermal growth factor receptor (EGF-R), the mammalian target of rapamycin (mTOR), the vascular endothelial growth factor receptor (VEGF-R) and the insulin-like growth factor receptor (IFG-R). Both small molecule and monoclonal antibody therapies directed against these targets are available. Furthermore, immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) and mutation analysis are available for profiling expression of pathway components, raising the possibility of individualized prognosis and therapy.
One receptor in particular, is both a prognostic factor and a therapeutic target in HNSCC. Upregulation of EGF-R expression and aberrant activation of kinase cascades downstream of this receptor occur early in the process of carcinogenesis and play a major role in malignant progression.1 The level of EGF-R expression correlates with recurrence and poor prognosis in HNSCC. A well tolerated anti-EGF-R monoclonal antibody, cetuximab, has shown remarkable activity against HNSCC, including statistically significant improvement in survival for patients with locally advanced disease treated with radiotherapy, leading to its regulatory approval for this disease.2 Unfortunately, despite survival advances achieved with EGF-R inhibitors, the majority (~60%) of patients with advanced disease are refractory to EGF-R directed therapies.3 One anticipated mechanism by which the current regimen may fail in some patients is the upregulation of escape pathways downstream of the EGF-R. A pathway of particular interest is the PI3/AKT/mTOR axis, within which the mTOR protein may be targeted by the tyrosine kinase inhibitor RAD001.
In order to investigate pathway components that may act as an escape mechanism while concurrently targeting a downstream kinase that may enable rescue from resistance to EGF-R directed therapies, we propose this prospective, phase II, single-arm, single-agent interventional clinical trial of RAD001 for patients with refractory SCCHN. The primary outcome is activity of RAD001 while secondary outcomes include safety, toxicity and extensive laboratory correlates to be performed on tumor tissues. By carrying out this clinic-translational trial of the novel mTOR inhibitor, RAD001, in patients with refractory SCCHN, we aim to explore mechanisms of activity of and resistance to inhibitors of the EGF-R pathway components while measuring the clinical activity of RAD001.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Everolimus 10 mg daily | Experimental | Drug: Everolimus 10mg dailyThe study of the efficacy of everolimus will proceed in two stages after the method of Simon1. In the first stage 15 patients will be accrued and treated. If 9 or fewer patients show clinical benefit the study will be terminated. If 10 or more patients show clinical benefit the study will proceed to the second stage, accruing an additional 26 patients. If the second stage is complete and a total of 29 or more patients show clinical benefit among the 41 patients treated, the treatment CBR for will be considered high enough to warrant further study. Conversely, if the evaluation of everolimus concludes at the first stage, or if 28 or fewer patients experience a clinical benefit after completing the second stage, the therapy will not be considered for further study. 1 |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Histologically or cytologically documented squamous cell CA of the head and neck
- Metastatic and/or recurrent head and neck cancer (not eligible for curative intent surgical or radiation therapy)
- Patients must have at least one measurable site of disease according to RECIST criteria that has not been previously irradiated. If the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation
- Performance status 0-2
- Age ≥18 years
Key exclusion criteria (21 listed)
- Patients currently receiving anticancer therapies or who have received anticancer therapies within 4 weeks of the start of study drug (including chemotherapy, radiation therapy, antibody based therapy, etc.)
- Patients, who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or patients that may require major surgery during the course of the study
- Prior treatment with any investigational drug within the preceding 4 weeks
- Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent, except corticosteroids with a daily dosage equivalent to prednisone ≤ 20 mg. However, patients receiving corticosteroids must have been on a stable dosage regimen for a minimum of 4 weeks prior to the first treatment with RAD001. Topical or inhaled corticosteroids are allowed.
- Patients should not receive immunization with attenuated live vaccines within one week of study entry or during study period
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 |
|---|---|---|
| Everolimus 10mg dailyAlso: EverolimusRAD001 is a pill that will be taken orally (by mouth), at a dose of 10 mg, once a day for 28 days. | Drug | Everolimus 10 mg daily |
Primary outcome
Clinical Benefit Rate (CBR)
Time frame: Up to 60 months
The number of patients with recurrent/refractory SCCHN (head and neck squamous cell carcinoma) treated with single-agent everolimus that, experience a Complete Response (CR) + number of patients that experience a Partial Response (PR ) + number of patients that experience Stable Disease (SD) / total evaluable patients.
3 secondary outcomes
Progression Free Survival (PFS)
Time frame: Up to 60 months
Overall Survival (OS)
Time frame: Up to 60 months
Objective Response Rate (ORR)
Time frame: Up to 60 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Squamous Cell Carcinoma of the Head and Neck
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingPhase 2
Proton Spatially Fractionated Radiotherapy or Photon Stereotactic Body Radiotherapy in Combination With Pembrolizumab Before Surgery for the Treatment of Locally Advanced and Radiation-Naive Locoregionally Recurrent Oral Cavity Cancer, OSPRI Trial
Locally Advanced Oral Cavity Squamous Cell Carcinoma, Locally Recurrent Oral Cavity Squamous Cell Carcinoma
RecruitingPhase 1/2
Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma
RecruitingPhase 2
A Single Arm Phase II Trial in p16-positive Oropharynx Cancer of Selective Dose De-escalation of nodAl VolumEs at Minimal Risk and Primary Site Disease (SAVED)
Head and Neck Cancer, Head and Neck Squamous Cell Cancer
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma
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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Everolimus 10mg daily in people with Squamous Cell Carcinoma of the Head and Neck, run by Julie E. Bauman, MD, MPH 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 15 inclusion and 21 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 19 Dec 2017. 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 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 19 Dec 2017). 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?
Clinical Benefit Rate (CBR) (time frame: Up to 60 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 19 Dec 2017.