Potentiation of Cetuximab by Tregs Depletion With CSA in Advanced Head & Neck Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01581970
Recruitment Status : Completed
First Posted : April 20, 2012
Last Update Posted : July 16, 2015
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

Brief Summary:
This is a feasibility study to assess the effectiveness of cetuximab when administered with low dose oral cyclophosphamide. Patients with metastatic squamous cell cancer of head and neck who have progressed on first line chemotherapy other than a cetuximab containing regimen will be treated with standard of care weekly cetuximab and twice daily low dose oral cyclophosphamide for 12 weeks.

Condition or disease Intervention/treatment Phase
Head and Neck Cancer Head and Neck Squamous Cell Carcinoma Drug: Cyclophosphamide Drug: Cetuximab Phase 2

Detailed Description:
In this study, patients with head and neck squamous cell carcinoma (HNSCC) will be given low-dose cyclophosphamide in combination with standard of care cetuximab. Tumor biopsies will be collected before and six weeks after treatment for measurement of tumor infiltration by effector cells, including CD8+ T cells, natural killer (NK) cells, and monocytes. In addition, the proportion of Tregs to effector cells will be measured in peripheral blood at the same time points.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 8 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Potentiation of Cetuximab by Tregs Depletion With Metronomic Cyclophosphamide in Metastatic Squamous Cell Cancers of Head and Neck
Study Start Date : June 2012
Actual Primary Completion Date : February 2015
Actual Study Completion Date : July 2015

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Cetuximab/low dose Cyclophosphamide
Safety population as defined by all patients receiving at least one treatment with cyclophosphamide on Day 1.
Drug: Cyclophosphamide
Patients will be given oral cyclophosphamide 50 mg twice daily to be self-administered starting the first day of therapy with weekly cetuximab for 12 weeks or until disease progression.
Other Name: Cytoxan

Drug: Cetuximab
The initial dose of cetuximab 400 mg/m^2 is administered over 120 minutes followed by weekly infusions of cetuximab 250 mg/m^2 intravenously (IV) over 60 minutes.
Other Name: Erbitux

Primary Outcome Measures :
  1. Progression Free Survival [ Time Frame: At 2 Years ]
    Progression of disease is defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.

Secondary Outcome Measures :
  1. Ratio of Tregs to Effector Cells [ Time Frame: 6 Weeks Post Treatment with Cyclophosphamide ]
    the ratio of Tregs to effector cells (NK cells, CD8+ lymphocytes, macrophages/monocytes) in tumor tissue as measured by immune-histochemistry (IHC) of tumor tissue

  2. Ratio of Tregs to Natural Killer (NK) Cells [ Time Frame: 6 Weeks Post Treatment with Cyclophosphamide ]
    the Ratio of Tregs to NK cells in peripheral blood as measured by flow cytometry

  3. Myeloid-derived suppressor cells in Tumor Tissue [ Time Frame: Week 6 ]
    Myeloid-derived suppressor cells in tumor tissue as measured by immune-histochemistry (IHC)

  4. Quality of Life Scores [ Time Frame: Comparison from Baseline to Week 6 and Week 12 ]
    Comparison of health related quality of life scores as measured by FACT-G: Functional Assessment of Cancer Therapy - General (constitutes the core of all subscales; the FACT-G can be used with patients of any tumor type)questionnaire.

  5. Overall survival [ Time Frame: 2 years ]
    Defined as patient alive at this time period.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically documented squamous cell carcinoma of the head and neck (irrespective of site of primary - nasopharyngeal, oral cavity, oropharyngeal, laryngeal or unknown primary) that is metastatic/incurable and has progressed on a first line chemotherapy regimen.
  • Progression of measurable disease within the last 6 weeks based on Response Evaluation Criteria in Solid Tumors (RECIST) criteria
  • If the patient has received prior treatment with anti-epidermal growth factor receptor (EGFR) therapy as a part of definitive therapy concurrent with radiation, the time from the last cetuximab exposure must be > 180 days.
  • Must be at least 30 days from prior treatment and have recovered from the reversible effects of previous anti-cancer treatment
  • Age ≥ 18 years
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1 or 2
  • Adequate bone marrow, renal and hepatic function within 14 days of study enrollment defined as:

    • Bone marrow: White blood cells (WBC) > 3,000/uL; absolute neutrophil count > 1,500/uL; platelets > 100,000/uL
    • Renal: creatinine ≤ 2.5 times the institutional upper limit of normal (ULN)
    • Hepatic: total bilirubin < 1.5 X institutional ULN; aspartate aminotransferase/alanine aminotransferase (AST[SGOT] and ALT[SGPT]) < 2.5 X institutional ULN
    • Albumin > 3.0 gm/dL
  • Women of childbearing potential and fertile men must be willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study and for 60 days after the last dose of study drug.
  • Voluntary written consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care

Exclusion Criteria:

  • Pregnant or lactating - females of child bearing potential must have a negative pregnancy test within 14 days of study enrollment as cyclophosphamide is Pregnancy Category D
  • History of another active primary invasive cancer within the previous 2 years, excluding non-melanoma skin cancer
  • The patient is receiving concurrent treatment with other anticancer therapy, including chemotherapy, immunotherapy, hormonal therapy, radiotherapy (RT), chemoembolization, or targeted therapy. Patients receiving palliative radiation therapy to bony metastases prior to the first dose of study medication are eligible.
  • Chronic steroid dependence
  • Known HIV-positive patients and those with other acquired/inherited immunodeficiency hepatitis B, hepatitis C, connective tissue disease, or other clinical diagnosis, ongoing or intercurrent illness that in the Investigator's opinion should preclude the subject from participation
  • History of gastrointestinal disease causing malabsorption or obstruction such as, but not limited to Crohn's disease, celiac sprue, tropical sprue, bacterial overgrowth/blind loop syndrome, gastric bypass surgery, strictures, adhesions, achalasia, bowel obstruction, or extensive small bowel resection
  • Inability to take medications by mouth
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition
  • Active autoimmune disease, chronic inflammatory condition, conditions requiring concurrent use of any systemic immunosuppressants or steroids. Mild-intermittent asthma requiring only occasional beta-agonist inhaler use or mild localized eczema will not be excluded.
  • Previous allo-transplant of any kind

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01581970

United States, Minnesota
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Principal Investigator: Gautam Jha, M.D. Masonic Cancer Center, University of Minnesota

Responsible Party: Masonic Cancer Center, University of Minnesota Identifier: NCT01581970     History of Changes
Other Study ID Numbers: 2012LS002
First Posted: April 20, 2012    Key Record Dates
Last Update Posted: July 16, 2015
Last Verified: July 2015

Keywords provided by Masonic Cancer Center, University of Minnesota:
head and neck cancer
metastatic squamous cell cancer

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Neoplasms, Squamous Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms by Site
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists