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Recurrent Hypopharyngeal Squamous Cell CarcinomaPhase 2MAESTRO HNNCT01256385

Temsirolimus With or Without Cetuximab in Patients With Recurrent and/or Metastatic Head and Neck Cancer Who Did Not Respond to Previous Therapy

A Phase 2 study testing Cetuximab, Laboratory Biomarker Analysis and Temsirolimus in people with Recurrent Hypopharyngeal Squamous Cell Carcinoma and Recurrent Laryngeal Squamous Cell Carcinoma, run by National Cancer Institute (NCI) at 24 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase II trial studies how well giving temsirolimus together with cetuximab works compared to temsirolimus alone in treating patients with recurrent and/or metastatic head and neck cancer who did not respond to previous therapy. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cetuximab, Laboratory Biomarker Analysis and Temsirolimus
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
86 participants
Where
24 sitesin 2 countries
Study dates
Nov 2010to Dec 2013
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically/cytologically confirmed diagnosis of squamous cell carcinoma of head and neck origin not amenable to curative intent therapy; information on prior exposure to cetuximab (duration, single agent/combined with chemotherapy/combined with radiation, best response, interval prior to study entry) will be collected
  • Progressive disease by RECIST criteria (or unequivocal clinical progression) on a cetuximab based therapy in any line of therapy for recurrent/metastatic disease; prior use of cetuximab for recurrent/metastatic disease is defined as palliative intent use either alone or in combination with chemotherapy with a minimum of 2 weeks of uninterrupted treatment with cetuximab; treatment with cetuximab during radiotherapy or chemoradiotherapy is not sufficient
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1
  • Presence of measurable lesions by RECIST: 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 computed tomography (CT) scan
  • Knowledge of the anatomic site of the original tumor (oropharynx versus non-oropharynx) or alternatively human papilloma virus (HPV) status; the trial will stratify patients by oropharynx versus non-oropharynx origin; HPV(+) tumors will be counted in the oropharynx cohort, HPV(-) tumors in the non-oropharynx cohort; at a later point all patients will undergo HPV testing as part of this trial; any widely used form of HPV testing is acceptable (including but not limited to HPV in situ hybridization [ISH], p16 testing [immunohistochemistry (IHC)], HPV16 testing, polymerase chain reaction [PCR], hybrid capture, etc)
  • Availability of formalin-fixed, paraffin-embedded (FFPE) tissue and blood
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  • FFPE: >=14 slides containing tumor, 18 recommended
  • 7-10 slides 5 um thick, AND 7-10 slides 10 um thick, and cut with a clean blade (use new blade if possible or clean vigorously to avoid RNA/DNA, RNase contamination)
  • Blood: two 10 cc ethylenediaminetetraacetic acid (EDTA) purple top tubes (blood); two 2 ml cryovials (serum)
  • Patients with human immunodeficiency virus (HIV), not requiring highly active antiretroviral treatment (HAART) therapy are eligible
  • Life expectancy of greater than 8 weeks
  • Leukocytes >= 2,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin within normal institutional limits (unless proven Gilbert's disease, which after principal investigator [PI] approval patient may be included)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
  • Creatinine within 1.5 X normal institutional limits
  • 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
  • Ability to understand and the willingness to sign a written informed consent document
  • Fasting glucose of =< 120 mg/dl and glycosylated hemoglobin (HbA1c) =< 7.5%

Who cannot join

  • Patients who have had chemotherapy or radiotherapy within 2 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 2 weeks earlier
  • Patients may not be receiving any other investigational agents
  • Patients with known, active brain metastases should be excluded from this clinical trial; patients with treated brain metastases stable for >= 12 weeks are eligible
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to temsirolimus or cetuximab
  • Concurrent life-threatening diseases: patients with diseases which with reasonable certainty do not limit life expectancy to 12 months or less are eligible; assessment of such concurrent illnesses should be by the principal investigator
  • Use of strong inhibitors/inducers of CYP3A4 is not permitted
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  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study
  • Breastfeeding should be discontinued if the mother is treated with temsirolimus
  • HIV-positive patients with normal immune function (CD4 count > 200) are eligible if there are no drug interactions with temsirolimus or cetuximab; patients with impaired immune function are ineligible due to the risk of additional immunosuppression from temsirolimus therapy
  • Concurrent administration of temsirolimus with vaccinations is to be avoided and a 14-day window from administration of the vaccine is advised; in emergent situations this policy may be revisited by the PI if deemed important for the patient's health
  • Poorly controlled hyperglycemia (HbA1C > 7.5%) or hyperlipidemia are exclusion criteria; hyperglycemia or hyperlipidemia need to be appropriately managed and controlled
  • Concurrent use of warfarin is allowed, but requires close monitoring of prothrombin time (PT)/international normalized ratio (INR)
  • Patients with clinically significant pneumonitis/pulmonary infiltrates unless there is a known and treatable cause for the condition

Trial locations and contacts

24 sites in 2 countries.

24 sites in 2 countries

United States23 sites

  • University of Michigan Comprehensive Cancer Center

    Ann Arbor, Michigan, 48109

  • University of Colorado Cancer Center - Anschutz Cancer Pavilion

    Aurora, Colorado, 80045

  • University of Maryland/Greenebaum Cancer Center

    Baltimore, Maryland, 21201

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • Northwestern University

    Chicago, Illinois, 60611

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • Decatur Memorial Hospital

    Decatur, Illinois, 62526

  • NorthShore University HealthSystem-Evanston Hospital

    Evanston, Illinois, 60201

  • Fort Wayne Medical Oncology and Hematology Inc-Parkview

    Fort Wayne, Indiana, 46845

  • Ingalls Memorial Hospital

    Harvey, Illinois, 60426

  • Indiana University/Melvin and Bren Simon Cancer Center

    Indianapolis, Indiana, 46202

  • University of Iowa/Holden Comprehensive Cancer Center

    Iowa City, Iowa, 52242

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

  • University of Wisconsin Hospital and Clinics

    Madison, Wisconsin, 53792

  • Loyola University Medical Center

    Maywood, Illinois, 60153

  • Illinois CancerCare-Peoria

    Peoria, Illinois, 61615

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Metro Minnesota Community Oncology Research Consortium

    Saint Louis Park, Minnesota, 55416

  • Mayo Clinic in Arizona

    Scottsdale, Arizona, 85259

  • Central Illinois Hematology Oncology Center

    Springfield, Illinois, 62702

  • Southern Illinois University School of Medicine

    Springfield, Illinois, 62702

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Mercy Hospital Saint Louis

    St Louis, Missouri, 63141

Other trials in United States

China1 site

  • Chinese University of Hong Kong-Prince of Wales Hospital

    Shatin, Hong Kong, OX1 3UJ

Other trials in China

About this study

Official title: A T1 Translational Multicenter Randomized Phase II Study of Temsirolimus Versus Cetuximab Plus Temsirolimus in Patients With Recurrent / Metastatic Head and Neck Cancer, Who Failed Prior EGFR Based Therapy

This phase II trial studies how well giving temsirolimus together with cetuximab works compared to temsirolimus alone in treating patients with recurrent and/or metastatic head and neck cancer who did not respond to previous therapy. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether giving temsirolimus together with cetuximab is more effective than giving temsirolimus alone.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Primary endpoint is progression free survival (PFS) of cetuximab/temsirolimus combination cohort (Arm A) compared to temsirolimus alone (Arm B).

SECONDARY OBJECTIVES:

  1. Progression-free survival (PFS) of cetuximab/temsirolimus combination group (Arm A) and temsirolimus control group (Arm B) compared to a historic control cohort.

II. Subgroup analysis of myofibroblast (+) cohort (PFS). III. Overall survival (OS). IV. Toxicities. V. Response (Response Evaluation Criteria in Solid Tumors [RECIST])/absolute tumor shrinkage (waterfall plot analysis).

VI. Activity of combination therapy (temsirolimus/cetuximab) after failure (progressive disease [PD]) of temsirolimus monotherapy.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive temsirolimus intravenously (IV) over 30-60 minutes and cetuximab IV over 1-2 hours once weekly. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive temsirolimus as in Arm A. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients with progressive disease may cross over to Arm A.

After completion of study therapy, patients are followed up for a minimum of 8 weeks and then once a year for 5 years.

Being tested
Cetuximab, Laboratory Biomarker Analysis, Temsirolimus
Medical subject headings
Squamous Cell Carcinoma of Head and Neck, Lymphoid Interstitial Pneumonia, Salivary Gland Neoplasms, Tongue Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CetuximabBiological

    Also called Chimeric Anti-EGFR Monoclonal Antibody, Chimeric MoAb C225, Chimeric Monoclonal Antibody C225, Erbitux

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • TemsirolimusDrug

    Also called CCI-779, CCI-779 Rapamycin Analog, Cell Cycle Inhibitor 779, Rapamycin Analog

    Given IV

Study groups in NCT01256385
Study groupRoleWhat they receive
Arm A (cetuximab and temsirolimus)ExperimentalPatients receive temsirolimus IV over 30-60 minutes and cetuximab IV over 1-2 hours once weekly. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Cetuximab; Other: Laboratory Biomarker Analysis; Drug: Temsirolimus
Arm B (temsirolimus)ExperimentalPatients receive temsirolimus as in Arm A. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients with progressive disease may cross over to Arm A.
Receives: Other: Laboratory Biomarker Analysis; Drug: Temsirolimus

What is being measured

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

  1. Progression-free Survival (PFS)

    Progression determined using RECIST criteria: >=20% increase in the sum of the longest diameters of target lesions from nadir, occurrence of new lesions, or progression of non-target lesions.

    Measured: From start of treatment to time of progression or death from any cause, assessed up to 5 years

Secondary outcomes (7)

  1. Overall Survival (OS)

    Time from randomization until death from any cause

    Measured: Up to 5 years

  2. Overall Response Rates (OR)

    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Statistics reported are for Overall Response (OR) = CR + PR.

    Measured: Up to 5 years

  3. PFS vs. Historical Control Cohort

    PFS at 4 months in Arm A and Arm B will each be compared with a 4-month historical control rate of 21.4%. The historical data appears in two publications, an ASCO abstract: Abidoye, ASCO Annual Meeting 2006: 5568 and de Souza, Davis, et al, Clin Cancer Res 2012; 18(8):2336-2343.

    Measured: From start of treatment to time of progression or death of any cause, assessed at 4 months

  4. Grade 3 or Higher Hematological Toxicity

    Incidence of hematological toxicities at least possibly related to study drug, graded based on Common Terminology Criteria for Adverse Events version 4

    Measured: Up to 5 years

  5. Percentage of Responses After Crossover From Control Arm to the Combination Arm, Assessed According to RECIST

    Percentage of responses (if any) after crossover from the control arm to the combination arm will be evaluated qualitatively. This is includes complete and partial responses, and is different from Outcome Measure 8 below, which includes complete and partial responses as well as stable disease.

    Measured: Up to 5 years

  6. PFS of Myofibroblast (+) Cohort

    Measured: From start of treatment to time of progression or death of any cause, assessed up to 5 years

  7. Percentage of Responses/Disease Stabilization for Patients Crossing Over to the Combination Therapy After Progressing on Arm B.

    Assessed according to RECIST. This is includes complete and partial responses as well as stable disease, and is different from Outcome Measure 6 above, which includes only complete and partial responses.

    Measured: Up to 5 years

Timeline

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

  1. First posted8 Dec 2010 (estimated)
  2. Study startNov 2010
  3. Primary completionDec 2013
  4. Study completionDec 2013

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
86 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01256385
Sponsor's protocol ID
NCI-2011-02596
Other IDs
NCI-2011-02596, CDR0000689896, UCCRC-10-428-B, 10-428-B, 10-428-B, 8692, N01CM00071, N01CM00099
Acronym
MAESTRO HN
Status last verified
Feb 2017
First submitted
7 Dec 2010
Last updated
27 Mar 2017

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cetuximab, Laboratory Biomarker Analysis and Temsirolimus in people with Recurrent Hypopharyngeal Squamous Cell Carcinoma and Recurrent Laryngeal Squamous Cell Carcinoma, run by National Cancer Institute (NCI) at 24 sites in 2 countries.

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 20 inclusion and 14 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 27 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 24 sites in United States, China. 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 6 Feb 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?

Progression-free Survival (PFS) (time frame: From start of treatment to time of progression or death from any cause, assessed up to 5 years). 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 NCT01256385.

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 27 Mar 2017.

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