Head and Neck CancerPhase 2NCT01581970
Potentiation of Cetuximab by Tregs Depletion With CSA in Advanced Head & Neck Cancer
A Phase 2 study testing Cyclophosphamide and Cetuximab in people with Head and Neck Cancer and Head and Neck Squamous Cell Carcinoma, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma
- What is being tested?
- Cyclophosphamide and Cetuximab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2012to Sep 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, 55455
About this study
Official title: Potentiation of Cetuximab by Tregs Depletion With Metronomic Cyclophosphamide in Metastatic Squamous Cell Cancers of Head and Neck
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.
Read the 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.
- Being tested
- Cyclophosphamide, Cetuximab
- Keywords
- head and neck cancer, metastatic squamous cell cancer
- Medical subject headings
- Head and Neck Neoplasms, Squamous Cell Carcinoma of Head and Neck, Neoplasms, Squamous Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CyclophosphamideDrug
Also called Cytoxan
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.
CetuximabDrug
Also called Erbitux
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.
| Study group | Role | What they receive |
|---|---|---|
| Cetuximab/low dose Cyclophosphamide | Experimental | Safety population as defined by all patients receiving at least one treatment with cyclophosphamide on Day 1. Receives: Drug: Cyclophosphamide; Drug: Cetuximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: At 2 Years
Secondary outcomes (5)
Aggregate Ratio of Tregs to Effector Cells for All Participants
The ratio of Tregs to effector cells (NK cells, CD 8+ lymphocytes, macrophages/monocytes) in tumor tissue as measured by immune-histochemistry (IHC) of tumor tissue for all Participants. Measure of central tendency was collected but the data is not accessible anymore because PI left institution and did not respond to requests for data.
Measured: 6 Weeks Post Treatment with Cyclophosphamide
Aggregate Ratio of Tregs to Natural Killer (NK) Cells for All Participants
the Ratio of Tregs to NK cells in peripheral blood as measured by flow cytometry for all Participants. Measure of central tendency was collected but the data is not accessible anymore because the PI left institution and did not respond to requests for data.
Measured: 6 Weeks Post Treatment with Cyclophosphamide
Myeloid-derived Suppressor Cells in Tumor Tissue
Myeloid-derived suppressor cells in tumor tissue as measured by immune-histochemistry (IHC)
Measured: Week 6
Quality of Life Scores
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.
At this point, the data is not able to be analyzed because the PI left the institution and did not respond to requests for data.
Measured: Comparison from Baseline to Week 6 and Week 12
Overall Survival
Defined as the number of patients alive two years out from study enrollment.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2012 (estimated)
- Study startJun 2012
- Primary completionSep 2015
- Study completionSep 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Head and Neck CancerStudies of the same condition, open and under way.
- More trials run by Masonic Cancer Center, University of MinnesotaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Masonic Cancer Center, University of Minnesota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Gautam Jha, M.D., Principal investigator, Masonic Cancer Center, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01581970
- Sponsor's protocol ID
- 2012LS002
- Status last verified
- Sep 2019
- First submitted
- 18 Apr 2012
- Last updated
- 11 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Potentiation of Cetuximab by Tregs Depletion With Metronomic Cyclophosphamide in Metastatic Squamous Cell Cancers of Head and Neck
- ClinicalTrials.gov ID
- NCT01581970
- Acronym / sponsor ID
- 2012LS002
- Keywords
- head and neck cancer, metastatic squamous cell cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Masonic Cancer Center, University of MinnesotaUniversity, hospital or other
- Study start
- Jun 2012
- Primary completion
- Sep 2015 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 20 Apr 2012 (estimated)
- Results
- Posted 11 Sep 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cetuximab/low dose Cyclophosphamide | Experimental | Drug: Cyclophosphamide, Drug: CetuximabSafety population as defined by all patients receiving at least one treatment with cyclophosphamide on Day 1. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CyclophosphamideAlso: CytoxanPatients 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. | Drug | Cetuximab/low dose Cyclophosphamide |
| CetuximabAlso: ErbituxThe 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. | Drug | Cetuximab/low dose Cyclophosphamide |
Primary outcome
Progression
Time frame: At 2 Years
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.
5 secondary outcomes
Aggregate Ratio of Tregs to Effector Cells for All Participants
Time frame: 6 Weeks Post Treatment with Cyclophosphamide
Aggregate Ratio of Tregs to Natural Killer (NK) Cells for All Participants
Time frame: 6 Weeks Post Treatment with Cyclophosphamide
Myeloid-derived Suppressor Cells in Tumor Tissue
Time frame: Week 6
Quality of Life Scores
Time frame: Comparison from Baseline to Week 6 and Week 12
Overall Survival
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gautam Jha, M.D. principal investigator
Masonic Cancer Center, University of Minnesota
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cyclophosphamide and Cetuximab in people with Head and Neck Cancer and Head and Neck Squamous Cell Carcinoma, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression (time frame: At 2 Years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Sep 2019.