Docetaxel Plus Lycopene in Castration Resistant, Chemotherapy-Naïve Prostate Cancer Patients

• Sponsor: University of California, Irvine (Other)
• Overall Status: Completed
• CT.gov ID: NCT01882985
• Collaborator: (none)
• Enrollment: 14
• Location: 1
• Arm: 1
• Actual Duration (Months): 70
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This phase II trial evaluated the impact of giving docetaxel together with lycopene supplements in treating patients with hormone-resistant prostate cancer not previously treated with chemotherapy. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Chemoprevention is the use of certain drugs, such as lycopene, to keep cancer from forming. Giving docetaxel together with lycopene may be an effective treatment for prostate cancer.

Condition or Disease	Intervention/Treatment	Phase
Adenocarcinoma of the Prostate; Recurrent Prostate Cancer; Stage I Prostate Cancer; Stage IIA Prostate Cancer; Stage IIB Prostate Cancer; Stage III Prostate Cancer	Drug: Docetaxel; Dietary Supplement: Lycopene	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To define the prostate-specific antigen (PSA) response rate according to the criteria of Bubley, et al. (>50% reduction from baseline) in subjects treated with a combination of docetaxel and lycopene.

SECONDARY OBJECTIVES:

I.To determine the objective response rate (ORR) according to modified RECIST criteria in patients with measurable disease, following treatment with docetaxel and lycopene.

1. To define the time to PSA progression, according to the response criteria of Scher, et al., in subjects treated with docetaxel and lycopene.

2. To determine the safety and tolerability of lycopene in combination with docetaxel.

3. To determine the effects of docetaxel + lycopene therapy on the functioning of the IGFR-I, selected biomarkers, and docetaxel blood levels in plasma and peripheral blood mononuclear cells (correlative studies).

OUTLINE:

Patients receive 75 mg/m2 docetaxel intravenously (IV) over 1 hour q 21 days and lycopene 30 mg capsules orally (PO) once daily on days 1-21. Treatment repeats every 21 days for at least 4 courses in the absence of disease progression or unacceptable toxicity.

Study Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study to Evaluate the Effects of Docetaxel Plus Lycopene in Castration Resistant, Chemotherapy-Naïve Prostate Cancer Patients
• Actual Study Start Date: Dec 1, 2010
• Actual Primary Completion Date: Oct 1, 2016
• Actual Study Completion Date: Oct 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (docetaxel and lycopene) Patients receive docetaxel IV over 1 hour on day 2 and lycopene PO once daily on days 1-21. Treatment repeats every 21days for at least 4 courses in the absence of disease progression or unacceptable toxicity.	Drug: Docetaxel; Given IV; Other Names: 114977-28-5 40466 628503 RP 56976 RP56976 Taxotere TXT ; Dietary Supplement: Lycopene; Given PO; Other Names: 407322 502-65-8 all-trans-Lycopene Lyc-O-Mato LYCO psi psi-Carotene

Outcome Measures

Primary Outcome Measures

1. Proporation of Subjects Achieving Partial Response, Stable Disease or Progressive Disease Based on PSA Response Rates [Up to week 12 of therapy]

   To define the prostate-specific antigen (PSA) response rate according to the criteria of Bubley, et al. in subjects treated with a combination of docetaxel and lycopene. Per criteria of Bubley, et al., PSA response rate is defined the number of subjects who achieve a >50% decline in PSA from baseline.

Secondary Outcome Measures

1. Objective Response Rate as Assessed by RECIST Criteria in Either Visceral or Lymph Node Metastases [Up to 4 years]

   The percent of subjects achieving an objective response by RECIST criteria in either visceral or lymph node metastases, and the percent achieving clinical complete disappearance of disease at any site, will be recorded.

2. Time to PSA Progression [Up to 4 years]

   The definition of time to PSA progression is the date (after the initiation of chemotherapy on day 2) that a 25% or greater increase, and an absolute increase of 2ng/mL or more, from the nadir PSA is documented. If there is no decrease in PSA following chemotherapy, then PSA progression is the date for documentation of a 25% increase from the baseline value along with an increase in absolute value of 2ng/mL or more.

3. Toxicity of Combined Docetaxel + Lycopene Therapy [Up to 4 years]

   The percentage of subjects experiencing grade 3-4 hematologic and non-hematologic toxicity will be recorded, as well as the reason for ending treatment. This outcome measure was not collected due to lack of funding.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patient must have a histological diagnosis of adenocarcinoma of the prostate and 2 rising pre-study PSA values >= 1 ng/ml at least 1 week apart within 28 days prior to enrollment

• Patients must be unresponsive to androgen-deprivation therapy (ADT), as indicated by a rising PSA level above the ADT nadir

• Patient must not have received chemotherapy, biologic therapy, or any other investigational drug for any reason within 28 days prior to start of therapy, and must have recovered from toxicities of prior therapy to grade 1 or less

• Patients must have been surgically or medically castrated; if the patient is being treated with medical castration, he must be willing to continue this treatment for the duration of the study; ADT should not be initiated, terminated, or dose-adjusted during the study

• Prior external beam radiation therapy (to less than 30% of the bone marrow only) is allowed; at least 28 days must have elapsed since the completion of radiation therapy and the patient must have recovered from side effects; prior treatment with samarium-153 or strontium-86 is allowed if at least eight weeks have elapsed since dosing, and all toxicities have resolved to grade 1; soft tissue disease which has been radiated in the prior 2 months is not assessable as measurable disease

• Patients may have received prior surgery; however, at least 21 days must have elapsed since completion of surgery and the patient must have recovered from all side effects

• Normal serum bilirubin and serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic pyruvate transaminase (SGPT) =< 1.5 x the institutional upper limit of normal obtained within 14 days prior to start of therapy; liver function tests should be evaluated prior to each treatment

• Serum creatinine =< 1.5 x the institutional upper limit of normal obtained within 14 days prior to start of therapy

• Men of child bearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter

• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-2

• Absolute neutrophil count >= 1,500/microliter (mcL)

• Hemoglobin of >= 8.0gm/dL

• White blood cell count > 2,500/mcL

• Platelets >= 100,000/mcL

• Patients with lower values may participate if, in the opinion of the investigator, the cytopenias are the result of bone marrow involvement with active prostate cancer

• Patients must be able to take oral medications

• All patients must be informed and must sign and give written informed consent in accordance with institutional and federal guidelines; patients who are unable to comply with study and/or follow-up procedures are ineligible

Exclusion Criteria:

• Uncontrolled brain or spinal cord metastases

• History of congestive heart failure or myocardial infarction within the previous six months

• History of allergy or hypersensitivity to any component of the study drugs

• Evidence or history of a bleeding diathesis or coagulopathy, including therapy-induced coagulopathy

• Presence of chronic diarrhea (> grade 1 by Common Toxicity Criteria (CTC)), short bowel syndrome, pancreatic insufficiency, or malabsorption

• Presence of any severe or uncontrolled concurrent medical condition which, in the opinion of the investigator, would increase the risk of serious toxicity from the study drugs

• Concurrent use of any vitamin, herb, or mineral supplements for at least 14 days prior to start of therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Chao Family Comprehensive Cancer Center	Orange	California	United States	92868

Sponsors and Collaborators

• University of California, Irvine

Investigators

• Principal Investigator: John P. Fruehauf, MD, PhD, University of California, Irvine

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: John P. Fruehauf, Professor of Clinical Medicine, University of California, Irvine
• ClinicalTrials.gov Identifier: NCT01882985
• Other Study ID Numbers: UCI 10-11 [HS# 2010-7765]; 2010-7765; NCI-2011-00037
• First Posted: Jun 21, 2013
• Last Update Posted: Jan 5, 2021
• Last Verified: Dec 1, 2020

• Keywords provided by John P. Fruehauf, Professor of Clinical Medicine, University of California, Irvine: docetaxel; lycopene; prostate cancer
• Additional relevant MeSH terms: Prostatic Neoplasms; Lycopene; Docetaxel

Study Results

Participant Flow

Arm/Group Title	Treatment (Docetaxel and Lycopene)
Arm/Group Description	Patients receive docetaxel IV over 1 hour on day 2 and lycopene PO once daily on days 1-21. Treatment repeats every 21days for at least 4 courses in the absence of disease progression or unacceptable toxicity. Docetaxel: Given IV Lycopene: Given PO
Period Title: Overall Study
STARTED	14
COMPLETED	12
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Treatment (Docetaxel and Lycopene)
Arm/Group Description	Patients receive docetaxel IV over 1 hour on day 2 and lycopene PO once daily on days 1-21. Treatment repeats every 21days for at least 4 courses in the absence of disease progression or unacceptable toxicity. Docetaxel: Given IV Lycopene: Given PO
Overall Participants	14
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	3 21.4%
>=65 years	11 78.6%
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	14 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 7.1%
Not Hispanic or Latino	11 78.6%
Unknown or Not Reported	2 14.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 7.1%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	11 78.6%
More than one race	0 0%
Unknown or Not Reported	2 14.3%
Region of Enrollment (Count of Participants)
United States	14 100%

Outcome Measures

1. Primary Outcome

Title	Proporation of Subjects Achieving Partial Response, Stable Disease or Progressive Disease Based on PSA Response Rates
Description	To define the prostate-specific antigen (PSA) response rate according to the criteria of Bubley, et al. in subjects treated with a combination of docetaxel and lycopene. Per criteria of Bubley, et al., PSA response rate is defined the number of subjects who achieve a >50% decline in PSA from baseline.
Time Frame	Up to week 12 of therapy

Outcome Measure Data

Analysis Population Description

One patient was inevaluable due to lost to follow up and one patient withdrew consent.

Arm/Group Title	Treatment (Docetaxel and Lycopene)
Arm/Group Description	Patients receive docetaxel IV over 1 hour on day 2 and lycopene PO once daily on days 1-21. Treatment repeats every 21days for at least 4 courses in the absence of disease progression or unacceptable toxicity. Docetaxel: Given IV Lycopene: Given PO
Measure Participants	12
Partial Response (PR)	9 64.3%
Stable Disease (SD)	2 14.3%
Progressive Disease (PD)	1 7.1%

2. Secondary Outcome

Title	Objective Response Rate as Assessed by RECIST Criteria in Either Visceral or Lymph Node Metastases
Description	The percent of subjects achieving an objective response by RECIST criteria in either visceral or lymph node metastases, and the percent achieving clinical complete disappearance of disease at any site, will be recorded.
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

Data was not collected for this objective.

Arm/Group Title	Treatment (Docetaxel and Lycopene)
Arm/Group Description	Patients receive docetaxel IV over 1 hour on day 2 and lycopene PO once daily on days 1-21. Treatment repeats every 21days for at least 4 courses in the absence of disease progression or unacceptable toxicity. Docetaxel: Given IV Lycopene: Given PO
Measure Participants	0

3. Secondary Outcome

Title	Time to PSA Progression
Description	The definition of time to PSA progression is the date (after the initiation of chemotherapy on day 2) that a 25% or greater increase, and an absolute increase of 2ng/mL or more, from the nadir PSA is documented. If there is no decrease in PSA following chemotherapy, then PSA progression is the date for documentation of a 25% increase from the baseline value along with an increase in absolute value of 2ng/mL or more.
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

Mean time to PSA progression

Arm/Group Title	Treatment (Docetaxel and Lycopene)
Arm/Group Description	Patients receive docetaxel IV over 1 hour on day 2 and lycopene PO once daily on days 1-21. Treatment repeats every 21days for at least 4 courses in the absence of disease progression or unacceptable toxicity. Docetaxel: Given IV Lycopene: Given PO
Measure Participants	12
Mean (Standard Deviation) [days]	335 (350.1)

4. Secondary Outcome

Title	Toxicity of Combined Docetaxel + Lycopene Therapy
Description	The percentage of subjects experiencing grade 3-4 hematologic and non-hematologic toxicity will be recorded, as well as the reason for ending treatment. This outcome measure was not collected due to lack of funding.
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

Data was not collected for this outcome measure.

Arm/Group Title	Treatment (Docetaxel and Lycopene)
Arm/Group Description	Patients receive docetaxel IV over 1 hour on day 2 and lycopene PO once daily on days 1-21. Treatment repeats every 21days for at least 4 courses in the absence of disease progression or unacceptable toxicity. Docetaxel: Given IV Lycopene: Given PO
Measure Participants	0

Adverse Events

Time Frame	86 days. Participants can then choose to continue treatment beyond this point until disease progression.
Arm/Group Title	Treatment (Docetaxel and Lycopene)
Arm/Group Description	Patients receive docetaxel IV over 1 hour on day 2 and lycopene PO once daily on days 1-21. Treatment repeats every 21days for at least 4 courses in the absence of disease progression or unacceptable toxicity. Docetaxel: Given IV Lycopene: Given PO
All Cause Mortality
	Treatment (Docetaxel and Lycopene)
	Affected / at Risk (%)	# Events
Total	2/14 (14.3%)
Serious Adverse Events
	Treatment (Docetaxel and Lycopene)
	Affected / at Risk (%)	# Events
Total	2/14 (14.3%)
Blood and lymphatic system disorders
Severe Neutropenia	1/14 (7.1%)
Cardiac disorders
Cardiac Arrhythmia	1/14 (7.1%)
Other (Not Including Serious) Adverse Events
	Treatment (Docetaxel and Lycopene)
	Affected / at Risk (%)	# Events
Total	9/14 (64.3%)
Blood and lymphatic system disorders
Anemia	2/14 (14.3%)
Proteinuria	1/14 (7.1%)
Neutropenia	2/14 (14.3%)
Hypertension	1/14 (7.1%)
Deep Vein Thrombosis	1/14 (7.1%)
Gastrointestinal disorders
Diarrhea	3/14 (21.4%)
Constipation	2/14 (14.3%)
General disorders
Fatigue	8/14 (57.1%)
Insomnia	3/14 (21.4%)
Pain	3/14 (21.4%)
Decreased Appetite	2/14 (14.3%)
Cracked Tooth	1/14 (7.1%)
Nausea	1/14 (7.1%)
Dry Mouth	1/14 (7.1%)
Dehydration	1/14 (7.1%)
Confusion	1/14 (7.1%)
Ecchymoses	1/14 (7.1%)
Blurred Vision	1/14 (7.1%)
Hot Flashes	1/14 (7.1%)
Dizziness	1/14 (7.1%)
Immune system disorders
Alopecia	3/14 (21.4%)
Infections and infestations
Left Eye Conjunctivitis	1/14 (7.1%)
Injury, poisoning and procedural complications
Edema	3/14 (21.4%)
Musculoskeletal and connective tissue disorders
Osteoporosis	1/14 (7.1%)
Nervous system disorders
Neuropathy	2/14 (14.3%)
Psychiatric disorders
Depression	1/14 (7.1%)
Respiratory, thoracic and mediastinal disorders
Cough	4/14 (28.6%)
Decrease taste	2/14 (14.3%)
Upper Respiratory Infection	1/14 (7.1%)
Allergic rhinitis	1/14 (7.1%)
Skin and subcutaneous tissue disorders
Onchomychosis	5/14 (35.7%)
Skin Changes	1/14 (7.1%)
Rash	2/14 (14.3%)
Dry Skin	1/14 (7.1%)
Vascular disorders
Hemorrhoids	1/14 (7.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.