Torisel in Addition to Standard Chemotherapy With Radiation for Advanced Head and Neck Cancer

This study has been withdrawn prior to enrollment.
(funding)
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Thomas Jefferson University
ClinicalTrials.gov Identifier:
NCT01326468
First received: March 29, 2011
Last updated: February 14, 2012
Last verified: February 2012
  Purpose

Patients with advanced head and neck cancer is at high risk of recurrence at the primary site or in the neck. Part of normal treatment is to treat such patients with chemotherapy and radiation. The chemotherapy can include Erbitux. The purpose of this study is to treat such patients with an additional agent, Torisel. This study tests the doses of Torisel that can be safely administered together with radiation and chemotherapy.


Condition Intervention
Head and Neck Cancer
Drug: Temsirolimus
Drug: Cetuximab
Drug: Cisplatin
Device: Radiation Therapy

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study of Chemoradiotherapy Plus Temsirolimus (Torisel) for Advanced Head and Neck Cancer

Resource links provided by NLM:


Further study details as provided by Thomas Jefferson University:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) of Torisel [ Time Frame: 7 weeks ] [ Designated as safety issue: Yes ]
    To determine the maximum tolerated dose (MTD) and a recommended phase II dose (RP2D) of Torisel (Torisel) when given with chemoradiotherapy (radiosensitized radiotherapy with cetuximab, cisplatin or both).


Secondary Outcome Measures:
  • Progression-Free Survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Progression-free survival (PFS) rate at 12 months (PFS12)


Enrollment: 0
Study Start Date: January 2011
Arms Assigned Interventions
Experimental: Cohort A - Temsirolimus with Cisplatin
Temsirolimus with cisplatin, Erbitux and radiation therapy
Drug: Temsirolimus
All patients will receive temsirolimus. The dose of temsirolimus in this study will range from 15-25 mg depending on the dose level. Temsirolimus will be infused over a 30-60 minute period once a week for the duration of radiation therapy.
Other Names:
  • Torisel
  • CCI-779
Drug: Cetuximab

All patients will receive cetuximab. An initial loading dose of cetuximab 400 mg/m2, intravenously over 120 minutes at least 4 days before radiation therapy but no more than 7 days before the start of radiation therapy.

Thereafter, cetuximab will be infused at 250 mg/m2 dose over 60 minutes weekly for the duration of radiation therapy.

Other Names:
  • IMC-C225
  • Erbitux
Drug: Cisplatin
All patients in Cohort A will receive cisplatin. The dose will be 20 mg/m2 or 30 mg/m2 depending upon the dose level.
Other Names:
  • cisplatinum
  • cis-diamminedichloroplatinum(II)
  • CDDP
  • Platinol
  • Platinol-AQ
Device: Radiation Therapy
Patients will be treated on a linear accelerator fitted with multi-leaf collimators with 1.6-2.3 Gy fractions delivered daily 5 days per week over 4-7 weeks to a cumulative dose of 66 Gy. A variance of +/- 10% in this nominal prescription dose is allowable and will depend on the extent of residual disease, at the discretion of the attending radiation oncologist.
Other Names:
  • IMRT
  • RT
  • radiation oncology
  • radiotherapy
  • XRT
Experimental: Cohort B - Temsirolimus
Temsirolimus with Erbitux and radiation therapy
Drug: Temsirolimus
All patients will receive temsirolimus. The dose of temsirolimus in this study will range from 15-25 mg depending on the dose level. Temsirolimus will be infused over a 30-60 minute period once a week for the duration of radiation therapy.
Other Names:
  • Torisel
  • CCI-779
Drug: Cetuximab

All patients will receive cetuximab. An initial loading dose of cetuximab 400 mg/m2, intravenously over 120 minutes at least 4 days before radiation therapy but no more than 7 days before the start of radiation therapy.

Thereafter, cetuximab will be infused at 250 mg/m2 dose over 60 minutes weekly for the duration of radiation therapy.

Other Names:
  • IMC-C225
  • Erbitux
Device: Radiation Therapy
Patients will be treated on a linear accelerator fitted with multi-leaf collimators with 1.6-2.3 Gy fractions delivered daily 5 days per week over 4-7 weeks to a cumulative dose of 66 Gy. A variance of +/- 10% in this nominal prescription dose is allowable and will depend on the extent of residual disease, at the discretion of the attending radiation oncologist.
Other Names:
  • IMRT
  • RT
  • radiation oncology
  • radiotherapy
  • XRT

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Cohort A:

  • Stage III or IVA-B HNC without prior RT except non-sm0kers with human papillomavirus (HPV) + nasopharynx and oropharynx. HPV+ oropharynx patients who have smoked regularly in the past 5 years are eligible.
  • Patients with local or regional recurrence after surgery alone are eligible, as long as the recurrent stage is III or IVA-B
  • Age > or = 18
  • Karnofsky performance status > 70
  • No severe active infection requiring intravenous antibiotics (oral antibiotics are allowable).
  • Adequate renal function (creatinine < 1.5 mg/dl), based upon blood work performed within 1 month prior to registration.
  • Adequate hepatic function (alkaline phosphatase and AST/ALT < 2 x ULN) based upon bloodwork performed within 1 month prior to registration.
  • Adequate bone marrow function (ANC > 1.5; platelets > 100K) based upon blood work performed within one month prior to registration.
  • Adequate cardiopulmonary function (no signs of acute coronary event and/or active CHF).
  • No plans for other concurrent radiation therapy, chemotherapy or biologic anti-cancer therapy.

Cohort B:

  • Platinum ineligible patients as defined by the multidisciplinary team.
  • Stage III or IVA-B HNC without prior RT except nonsmokers with HPV + nasopharynx and oropharynx. HPV+ oropharynx patients who have smoked regularly in the past 5 years are eligible.
  • Patients with local or regional recurrence after surgery alone are eligible, as long as the recurrent stage is III or IVA-B
  • Age > or = 18
  • KPS > 70
  • No severe active infection requiring intravenous antibiotics (oral antibiotics are allowable).
  • Adequate hepatic function (alkaline phosphatase and AST/ALT < 2 x ULN) based upon bloodwork performed within 1 month prior to registration.
  • Adequate bone marrow function (ANC > 1.5; platelets > 100K) based upon bloodwork performed within one month prior to registration.
  • Adequate cardiopulmonary function (no signs of acute coronary event and/or active CHF).
  • No plans for other concurrent radiation therapy, chemotherapy or biologic anti-cancer therapy.

Exclusion Criteria:

  • Current, recent (within 4 weeks of enrollment in this study) or planned participation in an experimental drug study other than this one.
  • KPS < 70%
  • Expected survival < 6 months
  • Early stage head and neck cancer as defined as T1N0 or T2N0 by AJCC 7th edition
  • Poorly controlled blood pressure, defined as systolic bp > 150 and/or diastolic bp > 100 despite medication.
  • Unstable angina.
  • NY Heart Association (NYHA) Grade II or greater congestive heart failure.
  • History of myocardial infarction or stroke within 6 months.
  • Clinically significant peripheral vascular disease.
  • Evidence of bleeding diathesis or coagulopathy.
  • Presence of brain or spinal cord metastases.
  • Major surgical procedure(s), open biopsy or significant traumatic injury within 14 days prior to initiation of radiation therapy and/or anticipation of need for major surgical procedure during the course of the study.
  • Minor surgical procedures such as needle/core biopsies, dental work, PEG placement, tracheostomy within 10 days prior to initiation of radiation therapy.
  • Carotid artery exposure or other signs of impending carotid artery hemorrhage.
  • History of abdominal fistula and/or gastrointestinal abdominal abscess within 6 months prior to enrollment.
  • Serious, non-healing wound, ulcer, or bone fracture.
  • Prior irradiation that would result in radiotherapy field "overlap."
  • Requirement for high dose oral anticoagulation (i.e., goal INR > 2.0). "Mini-dose" anticoagulation may be used to assist in patency of central venous lines. Subcutaneous low-molecular weight heparin is allowable.
  • No known allergies to any of the drug therapies being used in this protocol.
  • No pregnancy, lactation or inability to use medically acceptable birth control if of childbearing potential.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01326468

Sponsors and Collaborators
Thomas Jefferson University
Pfizer
Investigators
Principal Investigator: Voichita Bar-Ad, MD Thomas Jefferson University
  More Information

Additional Information:
No publications provided

Responsible Party: Thomas Jefferson University
ClinicalTrials.gov Identifier: NCT01326468     History of Changes
Other Study ID Numbers: 10D.133, 2009-44
Study First Received: March 29, 2011
Last Updated: February 14, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Thomas Jefferson University:
head and neck cancer
temsirolimus
cetuximab
cisplatin
radiation therapy

Additional relevant MeSH terms:
Head and Neck Neoplasms
Neoplasms by Site
Neoplasms
Cetuximab
Cisplatin
Sirolimus
Everolimus
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Antifungal Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on July 26, 2014