AzTrials
AzTrials

Squamous Cell Carcinoma of the Head and NeckPhase 1/2NCT01015664

Combination of Cisplatin, Cetuximab and Temsirolimus in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

A Phase 1/2 study testing temsirolimus, cisplatin and cetuximab in people with Squamous Cell Carcinoma of the Head and Neck, run by University of Tennessee Cancer Institute at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

This study will accrue in two "phases". During the first "phase" of the study, the optimal dose of temsirolimus in combination with cisplatin and cetuximab will be determined. It is expected that between 9-12 patients will be needed for this dose finding phase. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
temsirolimus, cisplatin and cetuximab
Type of treatment
Injection or infusion
How many people
11 participants
Where
1 siteUnited States
Study dates
Feb 2010to Dec 2012
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must be ≥ 18 years of age and have a histologically confirmed diagnosis of R/M SCCHN which is no longer amenable to curative surgical or radiation therapy.
  • Patients must sign a written informed consent form and HIPAA statement.
  • Patients must undergo biopsy for confirmation of R/M disease within 6 weeks (42 days) of study entry and be willing and able to comply with peripheral blood collections for the purpose of correlative studies. Biopsy of primary or metastatic site(s) is allowed, provided the site has not been previously irradiated.
  • Patients must have measurable disease as defined by RECIST.
  • Patients must have ECOG PS 0 or 1.
  • Patients must have adequate hematologic function as defined by an ANC ≥ 1,500, hemoglobin ≥ 10 g/dL, and a platelet count ≥ 75,000 obtained within 14 days prior to treatment.
Show all 12Show fewer
  • Patients must have adequate hepatic function as defined by a total bilirubin ≤ 1.5 mg/dL and AST (SGOT) and ALT (SGPT) ≤ 2 times the ULN obtained within 14 days prior to treatment.
  • Patients must have adequate renal function defined as a serum creatinine ≤ 1.5 mg/dL or calculated CrCl ≥ 55 mL/minute (calculations should be conducted using the Cockroft-Gault equation).
  • Patients must have adequate lipid control defined as a serum cholesterol ≤ 350 mg/dL and serum triglycerides ≤ 300 mg/dL obtained within 14 days prior to treatment.
  • Patients must not have received previous chemotherapy for the treatment of R/M SCCHN. Previous curative-intent treatment with chemotherapy, radiation therapy, chemoradiotherapy, or surgery for locoregional disease is allowed provided at least 3 months have elapsed since the completion of previous therapies and the patient has recovered from all treatment related toxicities.
  • Patients may have received prior radiation therapy for symptomatic sites of disease progression provided that ≥ 21 days have elapsed since treatment and the patient has recovered from any treatment related toxicities.
  • Males and females of reproductive potential must agree to use effective contraception for the duration of study participation.

Who cannot join

  • Patients with active or prior CNS metastases.
  • Patients with a history of previous hypersensitivity reaction to study drugs.
  • Patients with other active malignancies are excluded. Patients with a history of non-melanoma skin cancers, in-situ cervical cancer, definitively treated stage I or II cancers from which the patient is in remission, or a history of other malignancies from which the patient has been disease free for ≥ 5 years are permitted.
  • Concurrent therapy with any other anti-cancer treatments.
  • Ongoing or active clinically serious infection requiring IV antibiotics or active HIV infection.
  • Patients with a history of symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or any medical condition that could compromise the safety of the patient.
Show all 10Show fewer
  • Patients with, in the best judgment of the investigator, psychosocial, family, sociological, or geographical limitations which could impact the patient's ability to comply with study procedures.
  • Pregnant or lactating females.
  • Employees of the investigator or study center with direct involvement in this or other studies under the direction of the investigative team.
  • Patients currently taking any of the following medications are ineligible: phenytoin, carbamazepine, phenobarbitor, and/or rifampin as these are all strong Cyp3A4/5 inducers.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Boston Baskin Caner Foundation

    Memphis, Tennessee, 38138

Other trials in United States

About this study

Official title: A Phase I/II Trial of the Combination of Cisplatin, Cetuximab, and Temsirolimus in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

This study will accrue in two "phases". During the first "phase" of the study, the optimal dose of temsirolimus in combination with cisplatin and cetuximab will be determined. It is expected that between 9-12 patients will be needed for this dose finding phase. Once the optimal dose has been determined, an additional 41 patients will be enrolled in the second "phase" of the study. The primary purpose of second phase of the study is to learn what effects, good and/or bad, temsirolimus in combination with cisplatin and cetuximab has on recurrent or metastatic head and neck cancer.

Collection of additional blood and tissue specimens will make it possible to do special tests, which will provide us information about how tumors respond to the chemotherapy, how your body breaks down and processes the drug, how differences in the genetic makeup of each person affects how the drug may work and is processed in the body, and how the drug affects proteins and cells in the body. We hope to determine if results of the specialized tests done on blood will help to predict which patients are more likely to benefit from the use of the drugs used in this study.

Read the detailed description

The epidermal growth factor receptor (EGFR) pathway is a key molecular pathway in the pathogenesis of SCCHN. Cetuximab, a therapy targeting the EGFR pathway, has shown great promise in SCCHN. The EXTREME study found that by combining cetuximab to a regimen of cisplatin and 5-fluorouracil, PFS could be extended to 5.6 months from 3.3 months, and that overall survival increased to 10.1 months versus 7.4 months. While this study proved a survival benefit with the addition of cetuximab, there were high rates of Grade 3 or 4 toxicities to the chemotherapy backbone of high dose cisplatin with 5-fluorouracil.

The mammalian target of rapamycin (mTOR) pathway is activated when conditions favor cellular growth and proliferation. The PI3K-Akt pathway is one of the key modulators in the activation of mTOR. Phosphorylated Akt is detected in the majority of SCCHN tumors by immunohistochemistry.

Temsirolimus is an mTOR inhibitor that has been shown to have a synergistic effect with cisplatin and carboplatin in other tumor models. Due to the minimal toxicities associated with temsirolimus in clinical studies to date, this is an ideal agent to use in combination with other chemotherapies.

There is limited experience for the combination of EGFR inhibitors and mTOR inhibitors in human subjects. These agents have been combined with a suggested synergistic effect in preclinical models of colon cancer xenografts and cell lines from non-small cell lung, pancreas, colon, and breast cancers. Cetuximab has been safely combined with everolimus (on oral mTOR inhibitor) in human subjects.

There is sufficient evidence to suggest that the addition of the mTOR inhibitor, temsirolimus, may increase both the cytotoxicity seen from platinum-based chemotherapy as well as augment the effect of EGFR pathway inhibition from cetuximab, and possibly provide clinical benefit of its own. It is hypothesized that the combination of cisplatin, cetuximab, and temsirolimus will be an effective, well tolerated regimen for patients with R/M SCCHN.

Being tested
temsirolimus, cisplatin, 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.

  • temsirolimusDrug

    Also called Torisel

    10, 15, or 25 mg IV over 30 minutes on Days 1, 8, 15 and 22

  • cisplatinDrug

    Also called Platinol

    75 mg/m2 IV over 60 minutes on day 1

  • cetuximabDrug

    Also called Erbitux

    400 mg m2 on Day 1 of Cycle 1, then 250 mg/m2 IV over 60 minutes on Days 1, 8, 15, and 22

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase one - the outcome measure for determining the optimal dose will be determined by whether the subjects experience a dose limiting toxicity (DLT)

  2. Phase 2 - the outcome measure of Progression-Free Survival is defined as the time from first treatment to the documented progression of disease or death, whichever comes first.

Secondary outcomes (3)

  1. Overall response rate is defined as the proportion of patients achieving any response (CR + PR) compared to the total patient population.

  2. Disease control rate is defined as the proportion of patients who achieve a CR, PR, or SD (for ≥ 12 weeks) during study treatment compared to the total patient population.

  3. Overall survival is defined as the time from first treatment to the time of death, regardless of cause.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Nov 2009 (estimated)
  2. Study startFeb 2010
  3. Primary completionDec 2012
  4. Study completionDec 2012

Resources

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
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01015664
Sponsor's protocol ID
HN0209
Status last verified
Dec 2012
First submitted
17 Nov 2009
Last updated
17 Dec 2012
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing temsirolimus, cisplatin and cetuximab in people with Squamous Cell Carcinoma of the Head and Neck, run by University of Tennessee Cancer Institute 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 12 inclusion and 10 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 Dec 2012. 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?

The study was stopped early. Results are not available in the source record.

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?

Phase one - the outcome measure for determining the optimal dose will be determined by whether the subjects experience a dose limiting toxicity (DLT). The study lists 2 primary outcomes in all. 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 NCT01015664.

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 Dec 2012.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in