Fruit and Vegetable Extracts in Treating Patients With Stage I-IV, Stage IVA/IVB Head and Neck Cancer

• Sponsor: Wake Forest University Health Sciences (Other)
• Overall Status: Completed
• CT.gov ID: NCT00064298
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 134
• Locations: 28
• Arms: 2
• Actual Duration (Months): 63
• Patients Per Site: 4.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Cancer	Dietary Supplement: fruit and vegetable extracts; Dietary Supplement: placebo	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 134 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Prevention
• Official Title: A Phase II Randomized Placebo Controlled, Double Blinded Trial To Evaluate The Effects Of Fruit And Vegetable Extracts On Intermediate Biomarkers In Head And Neck Cancer Patients
• Actual Study Start Date: Jan 1, 2004
• Actual Primary Completion Date: Oct 1, 2008
• Actual Study Completion Date: Apr 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I - JuicePlus Patients receive oral fruit and vegetable extracts twice daily.	Dietary Supplement: fruit and vegetable extracts; Given orally
Placebo Comparator: Arm II - Control Patients receive oral placebo twice daily.	Dietary Supplement: placebo; Given orally

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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])

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	CCOP - Santa Rosa Memorial Hospital	Santa Rosa	California	United States	95403
2	Redwood Regional Medical Group	Santa Rosa	California	United States	95405
3	CCOP - Christiana Care Health Services	Newark	Delaware	United States	19713
4	MBCCOP - Howard University Cancer Center	Washington	District of Columbia	United States	20060
5	CCOP - Mount Sinai Medical Center	Miami Beach	Florida	United States	33140
6	University of Miami Sylvester Comprehensive Cancer Center - Miami	Miami	Florida	United States	33136
7	MBCCOP - JHS Hospital of Cook County	Chicago	Illinois	United States	60612
8	CCOP - Central Illinois	Decatur	Illinois	United States	62526
9	CCOP - Northern Indiana CR Consortium	South Bend	Indiana	United States	46601
10	Cedar Rapids Oncology Associates	Cedar Rapids	Iowa	United States	52403
11	MBCCOP - LSU Health Sciences Center	New Orleans	Louisiana	United States	70112
12	Feist-Weiller Cancer Center at Louisiana State University Health Sciences	Shreveport	Louisiana	United States	71130-3932
13	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan	United States	48106
14	CCOP - Beaumont	Royal Oak	Michigan	United States	48073-6769
15	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota	United States	55416
16	Missouri Baptist Cancer Center	Saint Louis	Missouri	United States	63131
17	CCOP - St. Louis-Cape Girardeau	Saint Louis	Missouri	United States	63141
18	CCOP - Cancer Research for the Ozarks	Springfield	Missouri	United States	65804
19	Alamance Cancer Center at Alamance Regional Medical Center	Burlington	North Carolina	United States	27216
20	Hugh Chatham Memorial Hospital	Elkin	North Carolina	United States	28621
21	CCOP - Southeast Cancer Control Consortium	Goldsboro	North Carolina	United States	27534-9479
22	Leo W. Jenkins Cancer Center at ECU Medical School	Greenville	North Carolina	United States	27835-6028
23	High Point Regional Hospital	High Point	North Carolina	United States	27261
24	Caldwell Memorial Hospital	Lenoir	North Carolina	United States	28645
25	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina	United States	27157-1030
26	CCOP - Greenville	Greenville	South Carolina	United States	29615
27	CCOP - Upstate Carolina	Spartanburg	South Carolina	United States	29303
28	Danville Regional Medical Center	Danville	Virginia	United States	24541

Sponsors and Collaborators

• Wake Forest University Health Sciences
• National Cancer Institute (NCI)

Investigators

• Study Chair: Steven A. Akman, MD, Wake Forest University Health Sciences

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Clinical trial summary from the National Cancer Institute's PDQ® database

Publications

None provided.

• Responsible Party: Wake Forest University Health Sciences
• ClinicalTrials.gov Identifier: NCT00064298
• Other Study ID Numbers: REBAWFU-60A02; U10CA081851
• First Posted: Jul 9, 2003
• Last Update Posted: Sep 28, 2021
• Last Verified: Sep 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Wake Forest University Health Sciences: 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
• Additional relevant MeSH terms: Head and Neck Neoplasms

Study Results

Participant Flow

Recruitment Details	Participants are recruited from NCI CCOP sites.

Arm/Group Title	Arm I - JuicePlus	Arm II - Control
Arm/Group Description	Patients receive oral fruit and vegetable extracts twice daily. fruit and vegetable extracts: Given orally	Patients receive oral placebo twice daily. placebo: Given orally
Period Title: Overall Study
STARTED	72	62
COMPLETED	66	57
NOT COMPLETED	6	5

Baseline Characteristics

Arm/Group Title	Arm I - JuicePlus	Arm II - Control	Total
Arm/Group Description	Patients receive oral fruit and vegetable extracts twice daily. fruit and vegetable extracts: Given orally	Patients receive oral placebo twice daily. placebo: Given orally	Total of all reporting groups
Overall Participants	72	62	134
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	51 70.8%	46 74.2%	97 72.4%
>=65 years	21 29.2%	16 25.8%	37 27.6%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	58	59	58
Sex: Female, Male (Count of Participants)
Female	11 15.3%	10 16.1%	21 15.7%
Male	61 84.7%	52 83.9%	113 84.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	7 9.7%	2 3.2%	9 6.7%
Not Hispanic or Latino	64 88.9%	60 96.8%	124 92.5%
Unknown or Not Reported	1 1.4%	0 0%	1 0.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 1.4%	0 0%	1 0.7%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	4 5.6%	7 11.3%	11 8.2%
White	64 88.9%	55 88.7%	119 88.8%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	3 4.2%	0 0%	3 2.2%
Region of Enrollment (Count of Participants)
United States	72 100%	62 100%	134 100%

Outcome Measures

1. Primary Outcome

Title	Expression of p27 Cell Cycle Regulatory Protein at Baseline and Week 12
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Arm I - JuicePlus	Arm II - Control
Arm/Group Description	Patients receive oral fruit and vegetable extracts twice daily. fruit and vegetable extracts: Given orally	Patients receive oral placebo twice daily. placebo: Given orally
Measure Participants	72	62
Baseline	18.6 (1.52)	15.1 (1.42)
12 weeks	17.0 (1.39)	14.5 (1.57)

2. Secondary Outcome

Title	Cell Proliferation (Ki-67) at Baseline and Week 12
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Arm I - JuicePlus	Arm II - Control
Arm/Group Description	Patients receive oral fruit and vegetable extracts twice daily. fruit and vegetable extracts: Given orally	Patients receive oral placebo twice daily. placebo: Given orally
Measure Participants	72	62
Baseline	26.8 (1.20)	26.2 (1.28)
12 Weeks	27.1 (1.43)	27.0 (1.55)

Adverse Events

Time Frame	12 weeks
Adverse Event Reporting Description	Sample size is number of participants with follow-up toxicity data recorded.
Arm/Group Title	Arm I - JuicePlus		Arm II - Control
Arm/Group Description	Patients receive oral fruit and vegetable extracts twice daily. fruit and vegetable extracts: Given orally		Patients receive oral placebo twice daily. placebo: Given orally
All Cause Mortality
	Arm I - JuicePlus		Arm II - Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm I - JuicePlus		Arm II - Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/68 (2.9%)		2/59 (3.4%)
Gastrointestinal disorders
Dehydration	1/68 (1.5%)	1	0/59 (0%)	0
General disorders
Pain	2/68 (2.9%)	2	0/59 (0%)	0
Fatigue	0/68 (0%)	0	1/59 (1.7%)	1
Musculoskeletal and connective tissue disorders
Ataxia	0/68 (0%)	0	1/59 (1.7%)	1
Nervous system disorders
Headache	1/68 (1.5%)	1	0/59 (0%)	0
Psychiatric disorders
Mood Change	0/68 (0%)	0	1/59 (1.7%)	1
Other (Not Including Serious) Adverse Events
	Arm I - JuicePlus		Arm II - Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/68 (30.9%)		16/59 (27.1%)
Gastrointestinal disorders
Diarrhea	4/68 (5.9%)	5	4/59 (6.8%)	5
Gas	0/68 (0%)	0	3/59 (5.1%)	4
Heartburn	7/68 (10.3%)	7	6/59 (10.2%)	12
Nausea	1/68 (1.5%)	1	3/59 (5.1%)	3
General disorders
Pain	3/68 (4.4%)	3	3/59 (5.1%)	3
SOB	4/68 (5.9%)	4	0/59 (0%)	0
Taste Alteration	3/68 (4.4%)	11	1/59 (1.7%)	2
Metabolism and nutrition disorders
Fatigue	3/68 (4.4%)	7	2/59 (3.4%)	7
Musculoskeletal and connective tissue disorders
Dysphagia	4/68 (5.9%)	5	0/59 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.