Adenocarcinoma of the Prostate, Recurrent Prostate Cancer, Stage IIA Prostate Cancer, Stage IIB Prostate Cancer, Stage III Prostate Cancer, Stage I Prostate Cancer
Conditions
Keywords
docetaxel, lycopene, prostate cancer
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.
Detailed description
PRIMARY OBJECTIVES: I. 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. II. To define the time to PSA progression, according to the response criteria of Scher, et al., in subjects treated with docetaxel and lycopene. III. To determine the safety and tolerability of lycopene in combination with docetaxel. IV. 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.
Interventions
DRUGDocetaxel
Given IV
DIETARY_SUPPLEMENTLycopene
Given PO
Sponsors
University of California, Irvine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
21 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
Docetaxel: Given IV
Lycopene: Given PO | 14 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Treatment (Docetaxel and Lycopene) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 11 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 11 Participants |
| Region of Enrollment United States | 14 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 14 |
| other Total, other adverse events | 9 / 14 |
| serious Total, serious adverse events | 2 / 14 |
Outcome results
Primary
Proporation of Subjects Achieving Partial Response, Stable Disease or Progressive Disease Based on PSA Response Rates
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
Population: One patient was inevaluable due to lost to follow up and one patient withdrew consent.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment (Docetaxel and Lycopene) | Proporation of Subjects Achieving Partial Response, Stable Disease or Progressive Disease Based on PSA Response Rates | Partial Response (PR) | 9 Participants |
| Treatment (Docetaxel and Lycopene) | Proporation of Subjects Achieving Partial Response, Stable Disease or Progressive Disease Based on PSA Response Rates | Stable Disease (SD) | 2 Participants |
| Treatment (Docetaxel and Lycopene) | Proporation of Subjects Achieving Partial Response, Stable Disease or Progressive Disease Based on PSA Response Rates | Progressive Disease (PD) | 1 Participants |
Secondary
Objective Response Rate as Assessed by RECIST Criteria in Either Visceral or Lymph Node Metastases
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
Population: Data was not collected for this objective.
Secondary
Time to PSA Progression
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
Population: Mean time to PSA progression
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment (Docetaxel and Lycopene) | Time to PSA Progression | 335 days | Standard Deviation 350.1 |
Secondary
Toxicity of Combined Docetaxel + Lycopene Therapy
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
Population: Data was not collected for this outcome measure.