Head and Neck CancerPhase 1/2NCT01009346
RAD001 in Combination With Cetuximab and Cisplatin in Recurrent and Metastatic SCCHN
A Phase 1/2 study testing RAD001, Cetuximab and Cisplatin in people with Head and Neck Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.
Trial summary
1.Phase I: To estimate the Maximum Tolerated Dose (MTD) of RAD001 in combination with cetuximab and cisplatin for treatment of metastatic squamous cell cancer of the head and neck (SCCHN). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Cancer
- What is being tested?
- RAD001, Cetuximab and Cisplatin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2009to Mar 2011
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have histologically or cytologically confirmed diagnosis of squamous cell carcinoma of the head and neck, with recurrent or metastatic disease.
- Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques or as >10 mm with spiral CT scan. See Section 11 for the evaluation of measurable disease.
- Patients must have had no prior monoclonal antibodies or small molecule tyrosine-kinase inhibitors for the treatment of recurrent or metastatic SCCHN. In addition, no prior chemotherapy for the treatment of recurrent or metastatic SCCHN is allowed.
- If the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation. Patients must be greater than or equal to 12 weeks from completion of prior curative intent therapy including surgery, radiation, or systemic anticancer therapy. If palliative radiation therapy is given for recurrent or metastatic disease, patients must be greater than or equal to four weeks from treatment.
- No concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix. Patients with prior history of malignancies must be disease free for greater than or equal to two years.
- Age >18 years.
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- Life expectancy of greater than 4.5 months.
- ECOG performance status <2 (Karnofsky >60%; see Appendix A).
- Patients must have normal organ and marrow function as defined below:
- leukocytes >3,000/mcL
- absolute neutrophil count >1,500/mcL
- platelets >100,000/mcL
- total bilirubin less than or equal to 1.5 X institutional upper limit of normal or within normal institutional limits. or
- AST(SGOT)/ALT(SGPT) <3.0 X institutional upper limit of normal - creatinine within normal institutional limits OR
- creatinine clearance >60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal 3.1.8
- As the investigational agent RAD001 requires enteral administration, patients must be able to receive adequate enteral nutrition by mouth or through a G-tube device.
- The effects of RAD001 on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- Ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- Patients may not be receiving any other investigational agents.
- Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to RAD001 or other agents used in the study.
- Patients receiving any medications or substances that are inhibitors or inducers of the isoenzyme CYP3A are ineligible. Lists including medications and substances known or with the potential to interact with the CYP3A isoenzymes are provided in the appendix.
- Patients receiving chronic treatment with systemic steroids or other immunosuppressive agents are ineligible.
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- Patients with a known hypersensitivity to RAD001 (everolimus) or other rapamycin (sirolimus, temsirolimus) or its excipients.
- Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 (e.g. ulcerative disease; uncontrolled nausea, vomiting, or diarrhea; malabsorption syndrome or small bowel resection).
- Patients with active bleeding diathesis or patients on oral anti-vitamin K agent (excluding low dose warfarin).
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, severely impaired lung function or psychiatric illness/social situations that would limit compliance with study requirements Severely impaired lung function is defined as spirometry and DLCO that is 50% of the normal predicted value and /or O2 saturation that is 88% or less on room air.
- Pregnant women are excluded from this study because RAD001 is a mTOR inhibitor with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with RAD001, breastfeeding should be discontinued. These potential risks may also apply to other agents used in this study.
- HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with RAD001. 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.
About this study
Official title: A Phase 1 Study of RAD001 in Combination w/ Cetuximab and Cisplatin as First-line Therapy in Recurrent & Metastatic Squamous Cell Cancer of the Head & Neck
1.Phase I: To estimate the Maximum Tolerated Dose (MTD) of RAD001 in combination with cetuximab and cisplatin for treatment of metastatic squamous cell cancer of the head and neck (SCCHN).
Secondary Objectives
1.To assess the toxicity of RAD001 in combination with weekly cetuximab and cisplatin on days 1 and 8 of each 28 day cycle in patients with recurrent or metastatic SCCHN,
Read the detailed description
This was a dose escalation study with RAD001 in combination with cetuximab and cisplatin in recurrent/metastatic SCCHN. Patients with ECOG performance status 0-2, with no prior systemic therapy for recurrent/metastatic SCCHN were enrolled. The dose levels for RAD001 were 2.5mg, 5mg or 10 mg administered oral daily, cetuximab 250mg/m2 weekly infusion, and cisplatin 40mg/m2 days 1 and 8. Each cycle was 28 days. Safety monitoring plan was outlined in the protocol and study calendar at specific time points. Response was evaluated with CT/MRI and PET scans every 2 cycles. DLT criteria and MTD was defined.
Dose escalation followed the conventional 3+3 design.
- Conditions
- Head and Neck Cancer
- Being tested
- RAD001, Cetuximab, Cisplatin, Carboplatin
- Medical subject headings
- Head and Neck Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RAD001Drug
Also called Everolimus
Dose Level -1 2.5mg/day
Dose Level 1 5mg/day*
Dose Level 2 10mg/day
MTD RAD001
CetuximabDrug
Also called Erbitux
250mg/m2/week
CisplatinDrug
Also called cisplatinum, CDDP, cis-diamminedichloroplatinum(II)
40mg/m2 Day 1, 8 every 28 days
CarboplatinDrug
Also called cis-Diammine(1,1-cyclobutanedicarboxylato)platinum(II)
Carboplatin will be administered on Day1 and Day 8 of each 28 day cycle to a target AUC of 3 over 30 minutes. Carboplatin will be dosed using the Calvert formula:
Total dose (mg) = (target AUC) x (glomerular filtration rate + 25) Creatinine clearance will be used to estimate the GFR. The Cockgroft-Gault formula will be used to estimate the creatinine clearance.
| Study group | Role | What they receive |
|---|---|---|
| RAD001 | Experimental | Daily RAD001 in combination with weekly cetuximab and cisplatin/ carboplatin on Day 1, 8 of each 28 day cycle. Receives: Drug: RAD001; Drug: Cetuximab; Drug: Cisplatin; Drug: Carboplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) of RAD001 in Combination With Cetuximab and Cisplatin.
MTD will be defined as a) the dose of RAD001 producing DLT in 0-1 out of 6 patients, or b) the dose level below the dose which produced DLT in <2 out of 6 patients, or c) the dose of 10mg po qd with less than 33% rate of DLT
Measured: 6 months
Secondary outcomes (1)
Progression Free Survival (PFS) of RAD001 in Combination With Weekly Cetuximab and Cisplatin.
Median number of months for which participants are free of progression after initiating treatment with RAD001 in combination with weekly cetuximab and cisplatin.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2009 (estimated)
- Study startOct 2009
- Primary completionMar 2011
- Study completionMar 2011
Why it stopped: Toxicity
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 Head and Neck CancerStudies of the same condition, open and under way.
- More trials run by Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Shanthi Marur, MD, Principal investigator, Johns Hopkins SKCCC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01009346
- Sponsor's protocol ID
- J0916
- Other IDs
- NA_00023951
- Status last verified
- Jun 2018
- First submitted
- 21 Oct 2009
- Last updated
- 17 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study of RAD001 in Combination w/ Cetuximab and Cisplatin as First-line Therapy in Recurrent & Metastatic Squamous Cell Cancer of the Head & Neck
- ClinicalTrials.gov ID
- NCT01009346
- Acronym / sponsor ID
- J0916
- Conditions
- Head and Neck Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Toxicity
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Study start
- Oct 2009
- Primary completion
- Mar 2011 (actual)
- Study completion
- Mar 2011 (actual)
- First posted
- 6 Nov 2009 (estimated)
- Results
- Posted 9 Jun 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
1.Phase I: To estimate the Maximum Tolerated Dose (MTD) of RAD001 in combination with cetuximab and cisplatin for treatment of metastatic squamous cell cancer of the head and neck (SCCHN).
Secondary Objectives
1.To assess the toxicity of RAD001 in combination with weekly cetuximab and cisplatin on days 1 and 8 of each 28 day cycle in patients with recurrent or metastatic SCCHN,
Detailed description
This was a dose escalation study with RAD001 in combination with cetuximab and cisplatin in recurrent/metastatic SCCHN. Patients with ECOG performance status 0-2, with no prior systemic therapy for recurrent/metastatic SCCHN were enrolled. The dose levels for RAD001 were 2.5mg, 5mg or 10 mg administered oral daily, cetuximab 250mg/m2 weekly infusion, and cisplatin 40mg/m2 days 1 and 8. Each cycle was 28 days. Safety monitoring plan was outlined in the protocol and study calendar at specific time points. Response was evaluated with CT/MRI and PET scans every 2 cycles. DLT criteria and MTD was defined.
Dose escalation followed the conventional 3+3 design.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| RAD001 | Experimental | Drug: RAD001, Drug: Cetuximab, Drug: Cisplatin, Drug: CarboplatinDaily RAD001 in combination with weekly cetuximab and cisplatin/ carboplatin on Day 1, 8 of each 28 day cycle. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Patients must have histologically or cytologically confirmed diagnosis of squamous cell carcinoma of the head and neck, with recurrent or metastatic disease.
- Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques or as >10 mm with spiral CT scan. See Section 11 for the evaluation of measurable disease.
- Patients must have had no prior monoclonal antibodies or small molecule tyrosine-kinase inhibitors for the treatment of recurrent or metastatic SCCHN. In addition, no prior chemotherapy for the treatment of recurrent or metastatic SCCHN is allowed.
- If the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation. Patients must be greater than or equal to 12 weeks from completion of prior curative intent therapy including surgery, radiation, or systemic anticancer therapy. If palliative radiation therapy is given for recurrent or metastatic disease, patients must be greater than or equal to four weeks from treatment.
- No concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix. Patients with prior history of malignancies must be disease free for greater than or equal to two years.
Key exclusion criteria (12 listed)
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- Patients may not be receiving any other investigational agents.
- Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to RAD001 or other agents used in the study.
- Patients receiving any medications or substances that are inhibitors or inducers of the isoenzyme CYP3A are ineligible. Lists including medications and substances known or with the potential to interact with the CYP3A isoenzymes are provided in the appendix.
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 |
|---|---|---|
| RAD001Also: EverolimusDose Level -1 2.5mg/day Dose Level 1 5mg/day* Dose Level 2 10mg/day MTD RAD001 | Drug | RAD001 |
| CetuximabAlso: Erbitux250mg/m2/week | Drug | RAD001 |
| CisplatinAlso: cisplatinum, CDDP, cis-diamminedichloroplatinum(II)40mg/m2 Day 1, 8 every 28 days | Drug | RAD001 |
| CarboplatinAlso: cis-Diammine(1,1-cyclobutanedicarboxylato)platinum(II)Carboplatin will be administered on Day1 and Day 8 of each 28 day cycle to a target AUC of 3 over 30 minutes. Carboplatin will be dosed using the Calvert formula: Total dose (mg) = (target AUC) x (glomerular filtration rate + 25) Creatinine clearance will be used to estimate the GFR. The Cockgroft-Gault formula will be used to estimate the creatinine clearance. | Drug | RAD001 |
Primary outcome
Maximum Tolerated Dose (MTD) of RAD001 in Combination With Cetuximab and Cisplatin.
Time frame: 6 months
MTD will be defined as a) the dose of RAD001 producing DLT in 0-1 out of 6 patients, or b) the dose level below the dose which produced DLT in <2 out of 6 patients, or c) the dose of 10mg po qd with less than 33% rate of DLT
1 secondary outcome
Progression Free Survival (PFS) of RAD001 in Combination With Weekly Cetuximab and Cisplatin.
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Shanthi Marur, MD principal investigator
Johns Hopkins SKCCC
1 site 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 RAD001, Cetuximab and Cisplatin in people with Head and Neck Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins 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 18 inclusion and 12 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 17 Jul 2018. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Jun 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (MTD) of RAD001 in Combination With Cetuximab and Cisplatin. (time frame: 6 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 17 Jul 2018.