Head and Neck Cancer
Conditions
Keywords
stage I squamous cell carcinoma of the hypopharynx, stage I squamous cell carcinoma of the larynx, stage I squamous cell carcinoma of the lip and oral cavity, stage I squamous cell carcinoma of the oropharynx, stage II squamous cell carcinoma of the hypopharynx, stage II squamous cell carcinoma of the larynx, stage II squamous cell carcinoma of the lip and oral cavity, stage II squamous cell carcinoma of the oropharynx, stage III squamous cell carcinoma of the hypopharynx, stage III squamous cell carcinoma of the larynx, stage III squamous cell carcinoma of the lip and oral cavity, stage III squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the hypopharynx, stage IV squamous cell carcinoma of the larynx, stage IV squamous cell carcinoma of the lip and oral cavity, stage IV squamous cell carcinoma of the oropharynx
Brief summary
RATIONALE: Chemoprevention therapy is the use of certain substances to try to prevent the development or recurrence of cancer. Fruit and vegetable extracts may be effective in preventing the recurrence or further development of head and neck cancer. PURPOSE: This randomized phase II trial is studying how well fruit and vegetable extracts work in preventing the recurrence of stage I, stage II, stage III, stage IVA, or stage IVB head and neck cancer.
Detailed description
OBJECTIVES: * Compare the disease-free survival of patients with stage I-IV (including stage IVA and IVB) head and neck cancer treated with fruit and vegetable extracts vs placebo. * Compare the effect of these extracts on biomarkers (p27 expression, cell proliferation of Ki-67, DNA damage, and T-cell function) in these patients. * Correlate changes in biomarkers with other factors (e.g., site and stage of the original tumors, tobacco/alcohol use, or depression) in patients treated with these extracts. * Compare serum carotenoids and antioxidant levels (vitamins A, C, and E) at baseline and posttreatment in patients treated with these extracts. OUTLINE: This is a randomized, placebo-controlled, double-blind study. Patients are stratified according to tobacco use (yes vs no), alcohol consumption (yes vs no), and tumor stage at diagnosis (I vs II vs III vs IVA vs IVB). Patients are randomized to 1 of 2 treatment arms. * Arm I: Patients receive oral fruit and vegetable extracts twice daily. * Arm II: Patients receive oral placebo twice daily. Treatment in both arms continues for 12 weeks in the absence of disease progression or unacceptable toxicity. Patients are followed annually for 5 years. PROJECTED ACCRUAL: A total of 200 patients (100 per treatment arm) will be accrued for this study within 18 months.
Interventions
DIETARY_SUPPLEMENTfruit and vegetable extracts
Given orally
DIETARY_SUPPLEMENTplacebo
Given orally
Sponsors
National Cancer Institute (NCI)
Wake Forest University Health Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Curatively treated stage I-IV (including stage IVA and IVB) squamous cell carcinoma of the upper aerodigestive tract of 1 of the following primary sites: * Oral cavity * Oropharynx * Hypopharynx * Larynx * Disease-free for at least 6 months and no more than 3 years after completion of surgery, radiotherapy, and/or chemotherapy * No synchronous tumors PATIENT CHARACTERISTICS: Age * 18 and over Performance status * Karnofsky 70-100% OR * Zubrod 0-1 Life expectancy * At least 6 months Hematopoietic * Hemoglobin ≥ 10 g/dL * WBC ≥ 3,000/mm\^3 * Platelet count ≥ 100,000/mm\^3 Hepatic * Bilirubin ≤ 1.5 mg/dL * SGOT ≤ 40 U/L * SGPT ≤ 56 U/L Renal * Creatinine ≤ 1.5 mg/dL Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No other malignancy within the past 5 years except curatively treated head and neck squamous cell carcinoma, nonmelanoma skin cancer, or carcinoma in situ of the cervix * No other serious medical or psychiatric illness that would preclude giving informed consent * No nausea ≥ grade 2 PRIOR CONCURRENT THERAPY: Biologic therapy * Not specified Chemotherapy * See Disease Characteristics * More than 6 months and less than 3 years since prior chemotherapy * No concurrent chemotherapy * No other concurrent chemopreventive agents Endocrine therapy * More than 6 months and less than 3 years since prior hormonal therapy Radiotherapy * See Disease Characteristics * More than 6 months and less than 3 years since prior radiotherapy * No concurrent radiotherapy Surgery * See Disease Characteristics * More than 6 months and less than 3 years since prior surgery * No concurrent surgery Other * More than 6 months and less than 3 years since prior investigational agents * More than 2 months since prior high-dose vitamins (i.e., 10 times the recommended daily allowance \[8,000-10,000 IU of vitamin A, 600 mg of vitamin C, or 80-100 IU of vitamin E\])
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Expression of p27 Cell Cycle Regulatory Protein at Baseline and Week 12 | baseline and 12 weeks | Expression of p27 cell cycle regulatory protein at baseline and week 12. p27 is measured continuously. Lower values are worse. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cell Proliferation (Ki-67) at Baseline and Week 12 | baseline and 12 weeks | Cell proliferation (Ki-67) at baseline and week 12. Ki67 is a cell proliferation associated nuclear protein. It is measured continuously. Higher values are worse. |
Countries
United States
Participant flow
Recruitment details
Participants are recruited from NCI CCOP sites.
Participants by arm
| Arm | Count |
|---|---|
| Arm I - JuicePlus Patients receive oral fruit and vegetable extracts twice daily.
fruit and vegetable extracts: Given orally | 72 |
| Arm II - Control Patients receive oral placebo twice daily.
placebo: Given orally | 62 |
| Total | 134 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 1 |
| Overall Study | Disease Progression | 2 | 1 |
| Overall Study | Lost to Follow-up | 2 | 2 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Arm I - JuicePlus | Arm II - Control | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 21 Participants | 16 Participants | 37 Participants |
| Age, Categorical Between 18 and 65 years | 51 Participants | 46 Participants | 97 Participants |
| Age, Continuous | 58 years | 59 years | 58 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 2 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 64 Participants | 60 Participants | 124 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 7 Participants | 11 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) White | 64 Participants | 55 Participants | 119 Participants |
| Region of Enrollment United States | 72 Participants | 62 Participants | 134 Participants |
| Sex: Female, Male Female | 11 Participants | 10 Participants | 21 Participants |
| Sex: Female, Male Male | 61 Participants | 52 Participants | 113 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 21 / 68 | 16 / 59 |
| serious Total, serious adverse events | 2 / 68 | 2 / 59 |
Outcome results
Primary
Expression of p27 Cell Cycle Regulatory Protein at Baseline and Week 12
Expression of p27 cell cycle regulatory protein at baseline and week 12. p27 is measured continuously. Lower values are worse.
Time frame: baseline and 12 weeks
Population: All randomized participants. Not all participants had p27 or Ki67 determined, so the sample sizes for the two outcomes differ from the total sample size.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm I - JuicePlus | Expression of p27 Cell Cycle Regulatory Protein at Baseline and Week 12 | Baseline | 18.6 percentage of cells | Standard Error 1.52 |
| Arm I - JuicePlus | Expression of p27 Cell Cycle Regulatory Protein at Baseline and Week 12 | 12 weeks | 17.0 percentage of cells | Standard Error 1.39 |
| Arm II - Control | Expression of p27 Cell Cycle Regulatory Protein at Baseline and Week 12 | Baseline | 15.1 percentage of cells | Standard Error 1.42 |
| Arm II - Control | Expression of p27 Cell Cycle Regulatory Protein at Baseline and Week 12 | 12 weeks | 14.5 percentage of cells | Standard Error 1.57 |
Secondary
Cell Proliferation (Ki-67) at Baseline and Week 12
Cell proliferation (Ki-67) at baseline and week 12. Ki67 is a cell proliferation associated nuclear protein. It is measured continuously. Higher values are worse.
Time frame: baseline and 12 weeks
Population: All participants randomized. Not all participants had p27 or Ki67 data so the sample sizes for the primary and secondary analyses differ from the overall sample size.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm I - JuicePlus | Cell Proliferation (Ki-67) at Baseline and Week 12 | Baseline | 26.8 percentage of cells | Standard Error 1.2 |
| Arm I - JuicePlus | Cell Proliferation (Ki-67) at Baseline and Week 12 | 12 Weeks | 27.1 percentage of cells | Standard Error 1.43 |
| Arm II - Control | Cell Proliferation (Ki-67) at Baseline and Week 12 | Baseline | 26.2 percentage of cells | Standard Error 1.28 |
| Arm II - Control | Cell Proliferation (Ki-67) at Baseline and Week 12 | 12 Weeks | 27.0 percentage of cells | Standard Error 1.55 |