NCT01256385

Brief 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. 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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
86

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Nov 2010

Typical duration for phase_2

Geographic Reach
2 countries

24 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 1, 2010

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

December 7, 2010

Completed
1 day until next milestone

First Posted

Study publicly available on registry

December 8, 2010

Completed
3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2013

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2013

Completed
3.2 years until next milestone

Results Posted

Study results publicly available

February 6, 2017

Completed
Last Updated

March 27, 2017

Status Verified

February 1, 2017

Enrollment Period

3.1 years

First QC Date

December 7, 2010

Results QC Date

October 4, 2016

Last Update Submit

February 23, 2017

Conditions

Recurrent Hypopharyngeal Squamous Cell CarcinomaRecurrent Laryngeal Squamous Cell CarcinomaRecurrent Laryngeal Verrucous CarcinomaRecurrent Lip and Oral Cavity Squamous Cell CarcinomaRecurrent Metastatic Squamous Cell Carcinoma in the Neck With Occult PrimaryRecurrent Nasal Cavity and Paranasal Sinus Squamous Cell CarcinomaRecurrent Nasopharyngeal Keratinizing Squamous Cell CarcinomaRecurrent Oral Cavity Verrucous CarcinomaRecurrent Oropharyngeal Squamous Cell CarcinomaRecurrent Salivary Gland CarcinomaSalivary Gland Squamous Cell CarcinomaSquamous Cell Carcinoma Metastatic in the Neck With Occult PrimaryStage IV Hypopharyngeal Squamous Cell CarcinomaStage IV Nasopharyngeal Keratinizing Squamous Cell CarcinomaStage IVA Laryngeal Squamous Cell CarcinomaStage IVA Laryngeal Verrucous CarcinomaStage IVA Lip and Oral Cavity Squamous Cell CarcinomaStage IVA Major Salivary Gland CarcinomaStage IVA Nasal Cavity and Paranasal Sinus Squamous Cell CarcinomaStage IVA Oral Cavity Verrucous CarcinomaStage IVA Oropharyngeal Squamous Cell CarcinomaStage IVB Laryngeal Squamous Cell CarcinomaStage IVB Laryngeal Verrucous CarcinomaStage IVB Lip and Oral Cavity Squamous Cell CarcinomaStage IVB Major Salivary Gland CarcinomaStage IVB Nasal Cavity and Paranasal Sinus Squamous Cell CarcinomaStage IVB Oral Cavity Verrucous CarcinomaStage IVB Oropharyngeal Squamous Cell CarcinomaStage IVC Laryngeal Squamous Cell CarcinomaStage IVC Laryngeal Verrucous CarcinomaStage IVC Lip and Oral Cavity Squamous Cell CarcinomaStage IVC Major Salivary Gland CarcinomaStage IVC Nasal Cavity and Paranasal Sinus Squamous Cell CarcinomaStage IVC Oral Cavity Verrucous CarcinomaStage IVC Oropharyngeal Squamous Cell CarcinomaTongue Carcinoma

Outcome Measures

Primary Outcomes (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.

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

Secondary Outcomes (7)

  • Overall Survival (OS)

    Up to 5 years

  • Overall Response Rates (OR)

    Up to 5 years

  • PFS vs. Historical Control Cohort

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

  • Grade 3 or Higher Hematological Toxicity

    Up to 5 years

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

    Up to 5 years

  • +2 more secondary outcomes

Study Arms (2)

Arm A (cetuximab and temsirolimus)

EXPERIMENTAL

Patients 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.

Biological: CetuximabOther: Laboratory Biomarker AnalysisDrug: Temsirolimus

Arm B (temsirolimus)

EXPERIMENTAL

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.

Other: Laboratory Biomarker AnalysisDrug: Temsirolimus

Interventions

CetuximabBIOLOGICAL

Given IV

Also known as: Chimeric Anti-EGFR Monoclonal Antibody, Chimeric MoAb C225, Chimeric Monoclonal Antibody C225, Erbitux, IMC-C225
Arm A (cetuximab and temsirolimus)

Correlative studies

Arm A (cetuximab and temsirolimus)Arm B (temsirolimus)

Given IV

Also known as: CCI-779, CCI-779 Rapamycin Analog, Cell Cycle Inhibitor 779, Rapamycin Analog, Rapamycin Analog CCI-779, Torisel
Arm A (cetuximab and temsirolimus)Arm B (temsirolimus)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • FFPE: \>=14 slides containing tumor, 18 recommended
  • 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)
  • +5 more criteria

You may not qualify if:

  • 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
  • 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
  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (24)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

University of Colorado Cancer Center - Anschutz Cancer Pavilion

Aurora, Colorado, 80045, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

Decatur Memorial Hospital

Decatur, Illinois, 62526, United States

Location

NorthShore University HealthSystem-Evanston Hospital

Evanston, Illinois, 60201, United States

Location

Ingalls Memorial Hospital

Harvey, Illinois, 60426, United States

Location

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

Illinois CancerCare-Peoria

Peoria, Illinois, 61615, United States

Location

Central Illinois Hematology Oncology Center

Springfield, Illinois, 62702, United States

Location

Southern Illinois University School of Medicine

Springfield, Illinois, 62702, United States

Location

Fort Wayne Medical Oncology and Hematology Inc-Parkview

Fort Wayne, Indiana, 46845, United States

Location

Indiana University/Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

Location

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Metro Minnesota Community Oncology Research Consortium

Saint Louis Park, Minnesota, 55416, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Mercy Hospital Saint Louis

St Louis, Missouri, 63141, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

Chinese University of Hong Kong-Prince of Wales Hospital

Shatin, Hong Kong, OX1 3UJ, China

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and NeckLymphoid Interstitial PneumoniaSalivary Gland NeoplasmsTongue Neoplasms

Interventions

CetuximabtemsirolimusSirolimus

Condition Hierarchy (Ancestors)

Carcinoma, Squamous CellCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsHead and Neck NeoplasmsNeoplasms by SiteMouth NeoplasmsMouth DiseasesStomatognathic DiseasesSalivary Gland DiseasesTongue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsMacrolidesLactonesOrganic Chemicals

Results Point of Contact

Title
Dr. Tanguy Seiwert
Organization
University of Chicago

Study Officials

  • Tanguy Seiwert

    University of Chicago Comprehensive Cancer Center P2C

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
LTE60
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 7, 2010

First Posted

December 8, 2010

Study Start

November 1, 2010

Primary Completion

December 1, 2013

Study Completion

December 1, 2013

Last Updated

March 27, 2017

Results First Posted

February 6, 2017

Record last verified: 2017-02

Locations