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

NCT01581970 | Completed Phase 2 Results

• 1 other identifier: 2012LS002
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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.

Conditions

Head and Neck Cancer; Head and Neck Squamous Cell Carcinoma

Keywords

head and neck cancer; metastatic squamous cell cancer

Outcome Measures

Primary Outcomes (1)

• Progression

  The number of patients without disease progression two years out from study enrollment. Progression of disease is defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria and is as at least a 20% increase in size of the lesion(s) being followed and/or the appearance of one or more new lesions.

  At 2 Years

Secondary Outcomes (5)

• Aggregate Ratio of Tregs to Effector Cells for All Participants

  6 Weeks Post Treatment with Cyclophosphamide

• Aggregate Ratio of Tregs to Natural Killer (NK) Cells for All Participants

  6 Weeks Post Treatment with Cyclophosphamide

• Myeloid-derived Suppressor Cells in Tumor Tissue

  Week 6

• Quality of Life Scores

  Comparison from Baseline to Week 6 and Week 12

• Overall Survival

  2 years

Study Arms (1)

Cetuximab/low dose Cyclophosphamide

EXPERIMENTAL

Safety population as defined by all patients receiving at least one treatment with cyclophosphamide on Day 1.

Drug: Cyclophosphamide; Drug: Cetuximab

Interventions

Cyclophosphamide DRUG

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.

Also known as: Cytoxan

Cetuximab/low dose Cyclophosphamide

Cetuximab DRUG

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.

Also known as: Erbitux

Cetuximab/low dose Cyclophosphamide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (1)

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck; Neoplasms, Squamous Cell

Interventions

Cyclophosphamide; Cetuximab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Gautam Jha
• Organization: Masonic Cancer Center, University of Minnesota

jhaxx014@umn.edu

612-624-5373

Study Officials

• Gautam Jha, M.D.

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2012
• First Posted: April 20, 2012
• Study Start: June 1, 2012
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2015
• Last Updated: September 11, 2019
• Results First Posted: September 11, 2019

Record last verified: 2019-09

Locations

US (1)