Clinical trial NCT01581970: Potentiation of Cetuximab by Tregs Depletion With CSA in Advanced Head & Neck Cancer
Official title: Potentiation of Cetuximab by Tregs Depletion With Metronomic Cyclophosphamide in Metastatic Squamous Cell Cancers of Head and Neck
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Head and Neck Cancer
Head and Neck Squamous Cell Carcinoma
Keywords: head and neck cancer
metastatic squamous cell cancer
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
First posted: 2012-04-20
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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 Regulatory T Cells (Tregs) to effector cells will be measured in peripheral blood at the same time points.

Eligibility criteria: 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

Primary outcomes:
measure: Progression
timeFrame: At 2 Years
Secondary outcomes:
measure: Aggregate Ratio of Tregs to Effector Cells for All Participants
timeFrame: 6 Weeks Post Treatment with Cyclophosphamide
measure: Aggregate Ratio of Tregs to Natural Killer (NK) Cells for All Participants
timeFrame: 6 Weeks Post Treatment with Cyclophosphamide
measure: Myeloid-derived Suppressor Cells in Tumor Tissue
timeFrame: Week 6
measure: Quality of Life Scores
timeFrame: Comparison from Baseline to Week 6 and Week 12
measure: Overall Survival
timeFrame: 2 years
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Masonic Cancer Center, University of Minnesota
state: Minnesota
Study officials:
affiliation: Masonic Cancer Center, University of Minnesota
name: Gautam Jha, M.D.
role: PRINCIPAL_INVESTIGATOR
References: