Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Pharmaceutical Solutions

Natriuretic Agents

Trastuzumab

Carboplatin

Docetaxel

Mannitol

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Concentrate for solution for infusion, sterile vial 150 mg, Day 1 Cycle 1 will be a loading dose of 8 mg/kg infused over 90 minutes. Subsequent infusions will follow every 3 weeks (i.e., cycled every 21 days) with a dose of 6 mg/kg administered over 30 to 90 minutes depending on tolerability, maximum of 6 cycles.

PF-05280014

Injection concentrate single-dose vials containing 20 mg (0.5 mL) or 80 mg (2 mL), each mL contains 40 mg docetaxel (anhydrous) and 1040 mg polysorbate 80, The starting dose of Taxotere® (docetaxel) will be 75 mg/m2 administered intravenously over 60 minutes every three weeks on Day 1 of each cycle (i.e., every 21 days), maximum 6 cycles.

Taxotere®

Lyophilized powder, single-dose vials containing 50 mg, 150 mg, and 450 mg of Carboplatin for administration by intravenous infusion (each vial contains equal parts by weight of Carboplatin and mannitol), starting dose 6 AUC, over 15 minutes or longer every three weeks on Day 1 of each cycle (i.e., every 21 days), maximum 6 cycles.

Paraplatin®

Concentrate for solution for infusion, sterile vial 150 mg, Day 1 Cycle 1 will be a loading dose of 8 mg/kg infused over 90 minutes. Subsequent infusions will follow every 3 weeks (i.e., cycled every 21 days) with a dose of 6 mg/kg administered over 30 to 90 minutes depending on tolerability, maximum 6 cycles.

Trastuzumab-EU

Pfizer CT.gov Call Center

The current study will compare PK, efficacy, safety, and immunogenicity of PF-05280014 (Trastuzumab-Pfizer) in combination with Taxotere® and Carboplatin (Paraplatin) versus Herceptin® (Trastuzumab-EU) approved in the EU in combination with Taxotere® and Carboplatin (Paraplatin) in patients with operable HER2 positive, breast cancer in the neoadjuvant setting. The hypothesis to be tested in this study is the percentage of patients with steady state Cycle 5 Ctrough (Cycle 6 pre-dose) \>20 µg/mL of trastuzumab-Pfizer is similar to EU-approved trastuzumab, using a margin of -12.5%.

A Study Of PF-05280014 Or Trastuzumab Plus Taxotere® And Carboplatin In HER2 Positive Breast Cancer In The Neoadjuvant Setting (REFLECTIONS B327-04)

A RANDOMIZED, DOUBLE-BLIND PHARMACOKINETIC STUDY OF PF-05280014 PLUS TAXOTERE (REGISTERED) AND CARBOPLATIN VERSUS HERCEPTIN (REGISTERED) PLUS TAXOTERE (REGISTERED) AND CARBOPLATIN FOR THE NEOADJUVANT TREATMENT OF PATIENTS WITH OPERABLE HER2-POSITIVE BREAST CANCER

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

The percentage of participants with Cycle 5 Ctrough (Cycle 6 pre-dose) \>20 μg/mL in each treatment group, the denominator being the number of participants in the per protocol population for each treatment group.

Samples of blood were taken pre-dose on Cycles 1, 2, 4, 5, and 6, and at 1 hour post dose on Cycles 1 and 5 for pharmacokinetic evaluation.

Following surgery after treatment completion, tumors were assessed as Complete Pathological Response, Partial Pathological Response, or No Pathological Response.

ORR was defined as Complete Response (CR), Partial Response (PR), Stable (SD), Progressive Disease (PD) or Indeterminate (IND). ORR was the percentage of participants who had CR or PR at Cycle 6/End of treatment.

The number of participants with positive (titer \>=1.00) pre-dose ADA samples, participants counted towards the total if for at least one sample, the ADA was positive.

The number of participants with positive (NAb response \>=1.48) pre-dose NAb samples, participants counted towards the total if for at least one sample, the NAb was positive.

Pfizer

Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.

Participants received a loading dose of 8 mg/kg of PF-05280014 on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.

Participants received a loading dose of 8 mg/kg of trastuzumab-EU on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.

Total

Age, Continuous

Female

Sex/Gender, Customized

All participants who were randomized into the study.

It was decided that the secondary study objective to explore the relationship between drug exposure and pCR for PF-05280014 versus trastuzumab-EU would not be analyzed.

All participants who were HER2+ and randomized into the study; and who had received 6 cycles of PF-05280014 or trastuzumab-EU treatment; and had no temporary delays of PF-05280014 or trastuzumab-EU treatment lasting more than 1 week; and had no other significant protocol deviations.

Percentage of Participants With Steady State Drug Concentration Ctrough (Cycle 6 Pre-dose) >20 µg/mL at Cycle 5.

Cycle 1/Day 1 0 hours N= 101, 88

Cycle 1/Day 1 1 hour N= 97, 80

Cycle 2/Day 21 0 hours N= 99, 88

Cycle 4/Day 63 0 hours N= 98, 89

Cycle 5/Day 84 0 hours N= 101, 87

Cycle 5/Day 84 1 hour N= 90, 80

Cycle 6/Day 105 0 hours N= 101, 89

All participants who were HER2+ and randomized into the study; and who have received 6 cycles of PF-05280014 or trastuzumab-EU treatment; and had no temporary delays of PF-05280014 or trastuzumab-EU treatment lasting more than 1 week; and had no other significant protocol deviations.

Mean Predose Trastuzumab-Pfizer and Trastuzumab-EU Concentrations at Cycles 1 Through 6.

Pathologic Complete Response (pCR) Defined as the Absence of Invasive Neoplastic Cells in the Breast and Lymph Nodes.

Objective Response Rate (ORR) Defined as the Percentage of Participants Having Complete or Partial Response at End of Treatment, Based on Radiographic Assessments of the Tumor.

Cycle 1 (n=113,112)

Cycle 2 (n=111,112)

Cycle 4 (n=108,109)

Cycle 6 (n=108,108)

All participants who received at least 1 dose of study drug.

Incidence of Anti-trastuzumab Antibodies (ADAs) at Cycles 1 Through 6.

Cycle 2 (n=110,112)

Cycle 4 (n=108,110)

Incidence of Neutralizing Antibodies (NAb) at Cycles 1 Through 6.

Participants received a loading dose of 8 mg/kg of PF-05280014 on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin area under the concentration versus time curve (AUC) 6 were administered on Day 1 of each cycle.

Study

Treatment

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Pemetrexed

Alimta®

Alain Vergnenegre, MD

Christos Chouaid, MD

The indication of chemotherapy of 2nd line treatment in advanced non small cell lung cancer is now well established. The two treatments of reference are pemetrexed (alimta) and docetaxel (taxotere). Effectiveness and toxicity of the two drugs are largely documented in the literature.

Economic analyses are currently one of the criteria used in medical decision, beside effectiveness, quality of life and toxicities.

However, Economical comparison shows significant variations in the acquisition costs of the two drugs. Consequently, it appears interesting to carry out a randomized prospective study with on exclusive economical criteria of judgment.

As there is no difference in the effectiveness between the two treatments, a cost-minimization analysis will be carried out to appreciate the ratio benefit/risks from an economical point of view (payer).

The main objective of this trial is of to compare, economically, the use of pemetrexed (alimta®) in 2nd line chemotherapy in advanced non-small cell lung cancer versus docetaxel (taxotere®).

150 patients will be selected for this trial which, after checking the eligibility criteria, will be randomized in two arms:

* Arm A: Taxotere 75 mg/m² every 3 weeks.
* Arm B : Alimta 500 mg/m² every 3 weeks.

Inclusion assessment.

* Clinical signs
* Blood cell count, renal and hepatic function (within 8 days)
* Chest X ray, CT scan or MRI scan, abdominal echography, and/or abdominal scan (within 28 days)
* Brain scan, bone scintigraphy and/or bone x ray (within 28 days)
* Bronchial endoscopy (within 28 days)
* EKG, echocardiography according to history

Follow-up assessment.

1. At each cycle

   * Clinical signs
   * Blood cell count at D1, D8, D15
   * Creatinine, serum electrolytes (K+, Ca++ ), SGOT, SGPT, total bilirubin, LDH, alkaline phosphate, total protein and albumin, EKG, Chest X-ray at D1
2. Follow-up each 2 months till PD
3. End of trial: Complete tumor assessment
4. Each objective response may be confirm 4 weeks later

Length ot the study.

* Patients in each arm will be treated until progression or toxicity or decision to stop the trial.
* Responder patient will be treated until 6 cycles. The follow-up assessment will be carried out each 2 months.

Response assessment. According to RECIST criteria.

Resource consumption.

1. Recording of volumes:

   * All the medication quantities will be recorded in mg. The chemotherapeutic products will be recorded in mg. All the concomitant treatments : RHO, anti-emetics, growth factors, antibiotics or adverse event treatments will be notified.
   * Hospitalizations for treatment and their categories ( inpatient, outpatient, home based treatment) will be noted.
   * All the hospitalizations for adverse events will be recorded (and their category). Grade 1-2 adverse events will be notified in the case report form. Hospitalizations for disease complications or progressions, curative or palliative radiation will be recorded.
2. Cost calculation :

   * All hospitalisations will be valued by DRGs or day hospitalisation prices, according to the country. Ambulatory care will be valued by appropriate country prices. The drug price will be done by pharmaceutical companies.

Pharmaco-economic Study of a Second Line Treatment in Advanced Non Small Cell Lung Cancer

A Randomized Cost-minimization Trial Comparing Pemetrexed (Alimta®) Versus Docetaxel (Taxotere®) as Second Line Treatment in Advanced Non Small Cell Lung Cancer (NSCLC): Study 05-06 of Groupe Français de Pneumo-Cancérologie (GFPC).

Groupe Francais De Pneumo-Cancerologie

University Hospital, Limoges

Marie SENGELEN

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Hypoglycemic Agents

Metformin

Hormones

Docetaxel (TAXOTERE®) will be administered at 75 mg/m2. Metformin (or placebo) is formulated into 850 mg tablets for oral administration and is to be dispensed twice a day on a continuous daily dosing schedule

Docetaxel (TAXOTERE®) will be administered at 75 mg/m2. Metformin is formulated into 850 mg tablets for oral administration and is to be dispensed twice a day on a continuous daily dosing schedule

METFORMIN

Placebo

TAXOTERE®

Jean-Marc FERRERO, PhD

Prostate cancer is the second leading cause of mortality in men, representing 10 deaths about of 100 cancers (INVS 2009). Treatment for metastatic prostate cancer, when becoming resistant to hormone-treatment, is mostly resumed to a relatively ineffective chemotherapy (Docetaxel/TAXOTERE®) (1). Recently, numerous clinical and preclinical works showed that Metformin could represent an excellent candidate for treatment of advanced prostate cancer. This is a widely prescribed drug, for type 2 diabetes, with clinical advantage of exhibiting very rare serious side effects. On the other hand, the use of this molecule in patients was associated with a decrease of tumors incidence, in particular prostate cancer (2). Numerous in vitro and in vivo studies support its role as an anti-cancer drug, in several cell lines (3). These experimental results are consistent with a clinical trial pilot study, performed in colorectal cancer, showing anti proliferative effect of Metformin (4). In the field of prostate, F. Bost in J.F. Tanti's team (INSERM U895, Nice) demonstrated that Metformin inhibits cell viability of human prostate cancer cells, via mTOR downregulation and decrease tumor growth in a xenograft model (5). Furthermore, preclinical data performed by this team showed that Metformin increased significantly apoptosis induced by TAXOTERE®. Therefore, by targeting specifically cancer cell metabolism, Metformin offers new promising therapeutic strategy.

The primary objective of this randomized study is to evaluate the biological efficacy of Metformin combination with TAXOTERE® in patients with metastatic hormone-refractory prostate cancer. To achieve this purpose, PSA response rate will be evaluated according to ASTRO definitions (Bubley, Carducci et al. 1999). Concurrently, secondary endpoints will be under investigation in order to evaluate the clinical response according to RECIST criteria, the overall and free-progression survival and the quality of life. Toxicity assessment will also be performed regarding to this drug combination.

Considering the well tolerability of Metformin and the first clinical and pre-clinical data reports of it use in cancer treatment, combining Docetaxel (TAXOTERE®) with Metformin may represent a promising strategy for treatment of hormone-refractory prostate cancer.

Prostate cancer: the current issues In developed countries, prostate cancer represents a major health issue and its incidence is rising globally, due to an aging society (Ferlay, Autier et al. 2007; Damber and Aus 2008). Indeed, over 70% of patients with prostate cancer are over the age of 65 years (Quinn and Babb 2002). In France, prostate cancer is the second most common cause of death from cancer in men and represents 10 deaths about of 100 by cancer (INVS 2009).

Although the screening and early detection have improved, a significant percentage of men diagnosed with prostate cancer will develop metastasis, reducing dramatically the 5-year relative survival (Jemal, Thun et al. 2008).

For patients with metastatic prostate cancer, the first-line treatment relies on androgen suppression following medical therapy or surgical orchiectomy. In about 80 percent of men, androgen ablation leads to symptomatic improvement; however, despite this treatment, the risk of relapse is at a median period of 24 months following hormone manipulation and the survival median is at about 3 years (1995; Sharifi, Dahut et al. 2005).

Clinical management of Castration-Resistant Prostate Cancer:

Currently, treatment for metastatic prostate cancer, when becoming unresponsiveness to androgen deprivation therapy, is mostly resumed to a relatively ineffective chemotherapy. Indeed, this disease state is considered the final stage of the disease in which the morbidity and mortality outlook is extremely bleak, and therapeutic options remain only palliative.

Combined Docetaxel (TAXOTERE®) and prednisone is currently considered the standard of care for men with castration-resistant prostate cancer and detectable metastatic disease, based largely on the simultaneous publication in October 2004 of two larges randomized controlled trials: SWOG 9916 et TAX 327, comparing this combination with the previous established standard of Mitoxantrone and prednisone (Petrylak, Tangen et al. 2004; Tannock, de Wit et al. 2004). While the use of Mitoxantrone led to pain reduction and quality of life improvement, without survival improvement (Tannock, Osoba et al. 1996), Docetaxel became the only approved systemic agent that has been shown to improve overall survival in conjunction with palliative benefits.

Docetaxel (TAXOTERE®) use was based on its ability to induce microtubules polymerization and on the discovery of Bcl-2 expression, an antiapoptotic protein, in prostate cancer cell line from metastatic hormone resistant patients. Indeed, this taxane by phosphorylating Bcl-2 induced apoptosis in cells expressing the protein (McDonnell, Navone et al. 1997).

In the phase III TAX-327 study, median survival was 18.9 month in the 3-week Docetaxel plus prednisone group and 16.5 month compared with mitoxantrone plus prednisone group. Correspondingly, clinically apparent improvements were also reported in terms of PSA response rate, pain response and quality of life, despite the increase in toxicity in the group that received Docetaxel. However, most adverse events associated with Docetaxel were of low grade and were bothersome rather than life-threatening (Tannock, de Wit et al. 2004). In this study, the median duration of the PSA response ranged from 7.7 and 8.2 months and did not differ significantly among the Docetaxel or Mitoxantrone group. In addition, the most common manifestations of metastatic prostate cancer, bone mestastasis that occurs in 65 to 75% (Bubendorf, Schopfer et al. 2000; Roudier, True et al. 2003) are also difficult to quantify accurately. Thus, in prostate cancer, PSA-based endpoint is used to surrogate clinical benefit and demonstrate drug activity in clinical trial.

However, regarding the limited and modest gains of Docetaxel based chemotherapy, trials are now focusing on improving the efficacy of Docetaxel by combining it with novel biological agents, but to date without demonstrable improvements (Ramsay and Leung 2009; Singh, Yam et al. 2010).

Interest of the associate Docetaxel (TAXOTERE®) with Metformin in Hormone-Refractory Prostate Cancer Metformin (N',N'-dimethylbiguanide) is a wildly used anti-diabetic drug which has the clinical advantage of having few side effects except rare lactic acidosis in patients with renal insufficiency (Lalau and Race 1999). Metformin is very effective in treating disorders marked by insulin-resistance. Several recent publications have shown that Metformin has anti-cancer properties

Epidemiologic and clinical evidences:

Several retrospective epidemiologic studies, in diabetic patients, showed that Metformin was associated with reduced risk of all cancer types (Evans, Donnelly et al. 2005; Currie, Poole et al. 2009). Thus, in a first retrospective cohort study of 62,809 type 2 diabetic patients treated in UK, the authors examined the risk of development of solid tumors in relation to treatment with oral agents, human insulin and insulin analogues. Results showed that people on insulin or sulfonylurea were more likely to develop solid cancers than those on Metformin. In this study, Metformin use was associated with lower risk of cancer of the colon or pancreas, but did not seem to affect the risk of breast or prostate cancer (Currie, Poole et al. 2009).

In another UK observational cohort study, cancer was diagnosed among 7.3% of 4,085 Metformin users compared with 11.6% of 4,085 diabetic comparators who had never used Metformin. After adjusting for baseline characteristics, there was still a significantly reduced risk of cancer associated with Metformin (37% lower than the non Metformin users group)(Libby, Donnelly et al. 2009).

In addition to these studies on all cancers, specific investigations reported that Metformin use was also associated with a significant decrease in the relative risk of specific cancers such as pancreatic cancer (Li, Yeung et al. 2009), hepatocellular carcinoma (Donadon, Balbi et al. 2010; Hassan, Curley et al. 2010), prostate (Wright and Stanford 2009) and breast cancers (Bodmer, Meier et al. 2010). Furthermore, in later years of follow up, high doses of Metformin were associated with the greatest reduction in risk of cancer, further supporting a protective effect of Metformin (Evans, Donnelly et al. 2005; Libby, Donnelly et al. 2009) (see review: Beck and Scheen 2010).

Concerning prostate cancer, a Finish and an American study, have shown a significant decrease of prostate cancer incidence in patients treated with Metformin (Murtola, Tammela et al. 2008; Wright and Stanford 2009).

Results from a population-based case-control study in men aged 35-74 years diagnosed with prostate cancer showed that Metformin use was more common in controls than in cases (4,7 versus 2,8%, p = 0,04) (Wright and Stanford 2009), resulting in a 44% risk reduction for prostate cancer.

A recent pilot clinical study, performed on 25 non-diabetic patients, have shown that Metformin reduced significantly the number of colorectal aberrant crypt foci (an endoscopic surrogate marker of colorectal cancer) (Hosono, Endo et al. 2010). This study demonstrates for the first time a beneficial effect of Metformin in anti-cancerous therapy.

Very recent preliminary data, presented at the 33rd Annual San Antonio Breast Cancer Symposium, are consistent with these previous studies showing that Metformin may have beneficial effects on cancer therapy (33rd annual San Antonio Breast Cancer Symposium, December 2010, San Antonio, USA). At the cellular level, combined treatment of metformine and erlotinib led to synergistic growth inhibitory effects in a proliferation assay and a clonogenic assay on breast cancer cells. The combined treatment also robustly reduced activation of EGFR, AKT, ERK and S6 signaling more than when either drug was used alone. Moreover, in a pilot mouse xenograft study, the combination treatment has been shown to shrink tumors by an average of approximately 25% (Meiers PJ 2010). Data from interim safety analysis demonstrated that preoperative metformin, in early stage breast cancer, significantly reduced cancer cell proliferation (as measured by change in Ki67 index) and induced apoptosis (TUNEL, cleaved caspase 3) (Niraula S 2010). Effects of its use was also associated with improved insulin resistance (Niraula S 2010). Those preliminary results showed that meformin was well tolerated with expected mild grade 1 toxicities and no significant QOL effects (Bonanni B 2010; Niraula S 2010). In addition, it has to be noted that no changes in insulin and in glycaemia levels had been reported with metformin use (Bonanni B 2010), except a slight decrease of BMI (Niraula S 2010).

Experimental evidences:

In a xenograft model, Metformin has been shown to inhibit human prostate cancer cell proliferation as well as to decrease significantly tumor growth (Ben Sahra, Laurent et al. 2008). Other investigations demonstrated a direct inhibitory effect of Metformin on the growth of cancer cells originated from breast (Zakikhani, Dowling et al. 2006), ovary (Rattan, Giri et al. 2009), pancreas (Kisfalvi, Eibl et al. 2009) and colon (Buzzai, Jones et al. 2007) as well as on tumor growth in mice models (see review: Ben Sahra, Le Marchand-Brustel et al. 2010)). At the cellular level, Metformin provoked a cell arrest at the G0/G1 stage and induced apoptosis in several cell types.

The mTOR and Akt pathways are frequently activated in cancers, which has been correlated with a poor prognosis. In prostate cancer cells, Tanti's team showed that Metformin strongly inhibited mTOR pathway and down regulated cyclin D1 expression, a protein associated with cellular transformation (Ben Sahra, Laurent et al. 2008). Preclinical preliminary studies, performed in this laboratory, also showed that, combinating Metformin with TAXOTERE®, potentiated significantly the anti-proliferative effect of TAXOTERE®. Furthermore, Metformin also increased TAXOTERE®-induced apoptosis in prostate cancer cells.

2. Location of the work in the context of the current knowledge :

Therefore, by targeting specifically cancer cell metabolism, Metformin offers new promising therapeutic strategies. Indeed, Metformin is very well tolerated and has been used for more than 30 years for the treatment of type II diabetes. The efficiency of Metformin as an anti-proliferative and an anti-tumoral agent in mice and according to recent clinical reports in breast field, raise the possibility that Metformin could be a potential candidate in novel treatment for cancer, especially in human prostate cancer. Here, we hypothesized that Metformin may improve TAXOTERE® efficacy in patient with hormone refractory prostate cancer.

The primary objective of this randomized study is to evaluate the biological efficacy of Metformin combination with TAXOTERE® in patients with metastatic hormone-refractory prostate cancer. To achieve this purpose, PSA response rate will be evaluated according to ASTRO definitions (Bubley, Carducci et al. 1999). Concurrently, secondary endpoints will be under investigation in order to evaluate the clinical response according to RECIST criteria, the overall and free-progression survival and the quality of life. Toxicity assessment will also be performed regarding to this drug combination.

Considering the well tolerability of Metformin and the first clinical and pre-clinical data reports of it use in cancer treatment, combining Docetaxel (TAXOTERE®) with Metformin may represent a promising strategy for treatment of hormone-refractory prostate cancer.

Metformin-Docetaxel Association in Metastatic Hormone-refractory Prostate Cancer

A Multicentric, Randomized, Phase II Study Evaluating the Combination of METFORMIN With TAXOTERE®+Metformine Placebo Versus TAXOTERE®+Metformin for the Treatment of Metastatic Hormone-refractory Prostate Cancer.

Centre Antoine Lacassagne

Adenocarcinoma

Anti-Inflammatory Agents

Prednisone

Glucocorticoids

Hormone Antagonists

Antineoplastic Agents, Hormonal

75 mg/m\^2 Day 1 of every 21-day cycle by vein for 4 cycles prior to surgery.

Taxotere

Lance Pagliaro, MD

Objectives:

Primary:

* To evaluate the association of the probability of increase in phosphorylation of platelet-derived growth factor receptor (PDGFR) of \> 0.5 in peripheral blood leucocytes following pre-operative docetaxel chemotherapy, with progression-free survival in localized castration-resistant prostate cancer (CRPC)

Secondary:

* To evaluate the association of the probability of increase in phosphorylated platelet-derived growth factor receptor (PDGFR) expression in peripheral blood leucocytes \> 0.5 with indices of tumor regression including PSA-decline by 50% and measures of objective regression of tumor by transrectal MRI following pre-operative docetaxel therapy.
* Explore associations of probability of increase in phosphorylated PDGFR in peripheral blood leucocytes following pre-operative docetaxel therapy with plasma PDGF kinetics and spatial and quantitative PDGF and phosphorylated PDGFR expression in tumor and stromal compartments in resected specimens.
* Evaluate the association of probability of increase in phosphorylated PDGFR expression in peripheral blood leucocytes following pre-operative docetaxel chemotherapy with overall survival outcomes.
* Assess global quality of life measures at baseline and 6 and 12 months post-operatively.
* Create a tissue archive comprising tumor and peripheral blood specimens as a suitable resource for future genomic and proteomic studies.

The Study Drugs:

Docetaxel is designed to stop the growth of cancer cells, which may cause the cells to die. It is believed to be weakly effective at killing blood vessels in cancer cells as well.

Prednisone and docetaxel are commonly used to treat prostate cancer.

Study Drug Administration:

If you are found to be eligible to take part in this study, on Day 1 of every 21-day study "cycle", you will receive docetaxel through a needle in your vein over 1 hour.

Everyday, you will take prednisone by mouth 2 times a day (in the morning and evening). You should take prednisone with meals.

You will take dexamethasone by mouth at 12 hours and 6 hours before you receive docetaxel. This is to help reduce the risk of any allergic reaction and fluid retention. It is important that you take this drug on schedule.

Study Visits:

On Day 1 of each cycle, the following tests and procedures will be performed:

* You will have a physical exam, including measurement of your weight.
* Your performance status will be recorded.
* You will be asked about any drugs or treatments you may be receiving.
* You will be asked about any side effects you have experienced since your last visit.

Blood (about 2 teaspoons) will be drawn for routine tests and to test for PSA and testosterone levels.

On Day 1 of Cycle 3, blood (about 2 teaspoons) will be drawn to test for PDGFR and PDGF levels.

Surgery:

If you complete 2 cycles or more, you will be eligible to have surgery as part of this study.

If you are eligible, no more than 21 days after your last dose of docetaxel, you will have surgery to remove your prostate gland. You will sign a separate consent for this surgery, which will describe the procedure and its risks in detail.

Before surgery, probably at your pre-surgical visit, blood (about 2 teaspoons) will be drawn to test for PDGFR and PDGF levels.

Length of Study:

You will take the study drug for up to 4 cycles before having surgery. You will be off study treatment after you have surgery. You will be taken off study early if you experience intolerable side effects or the disease gets worse.

This is an investigational study. Docetaxel given with prednisone is commercially available and FDA approved for the treatment of prostate cancer.

Up to 28 participants will take part in this study. All will be enrolled at M. D. Anderson.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study Of PF-05280014 Or Trastuzumab Plus Taxotere® And Carboplatin In HER2 Positive Breast Cancer In The Neoadjuvant Setting (REFLECTIONS B327-04)	NCT02187744	Early Breast Ca...	PF-05280014 Taxotere® Paraplatin® Trastuzumab-EU Taxotere® Paraplatin®	18 Years -	Pfizer
Pharmaco-economic Study of a Second Line Treatment in Advanced Non Small Cell Lung Cancer	NCT00284778	Carcinoma, Non-...	Alimta® Taxotere®	18 Years - 70 Years	University Hospital, Limoges
A Study Of PF-05280014 Or Trastuzumab Plus Taxotere® And Carboplatin In HER2 Positive Breast Cancer In The Neoadjuvant Setting (REFLECTIONS B327-04)	NCT02187744	Early Breast Ca...	PF-05280014 Taxotere® Paraplatin® Trastuzumab-EU Taxotere® Paraplatin®	18 Years -	Pfizer
Metformin-Docetaxel Association in Metastatic Hormone-refractory Prostate Cancer	NCT01796028	Prostatic Neopl...	METFORMIN Placebo TAXOTERE®	18 Years -	Centre Antoine Lacassagne
Preoperative Docetaxel for Localized Progressive Castration-resistant Prostate Cancer (CRPC)	NCT00811031	Prostate Cancer	Taxotere Prednisone	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for taxotere®

Every month we try and update this database with for taxotere® cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for taxotere®

Every month we try and update this database with for taxotere® cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for taxotere® cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.