Intermittent Hormonal Therapy With Leuprorelin and Flutamide in the Treatment of Stage D2 or TxNxM1b,c

NCT00817739 | Completed Phase 2

• 2 other identifiers: TAP IIb/95/022 - EC210U1111-1169-6769
• Study Type: interventional
• Target: 341
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is aimed at evaluating the effects of intermittent hormonal treatment with complete androgen suppression (Leuprorelin 3.75 milligram \[mg\] sustained release \[SR\] and Flutamide) in patients presenting with stage D2 or Tx Nx M1 ≠ M1a metastatic prostrate cancer, with a prostate specific antigen (PSA) level 5-fold higher than normal (PSA greater than or equal to \[≥\] 20 nanogram per milliliter \[ng/mL\], as quantitated by the Hybritech radioimmunoassay) and with a subsequent decline to normal (PSA less than \[\<\] 4 ng/mL) during the initial 6 months of induction treatment. The results will be compared with those obtained after continuous hormonal therapy with complete androgen suppression.

Conditions

Prostatic Neoplasms

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (2)

• Median Overall Survival

  Median Overall survival is defined as the number of days from date of inclusion to the date of death. For subjects who do not die, survival will be censored at the date of last contact.

  Randomization (Month 6) up to Week 396 after randomization

• Median Progression-Free Survival

  Median Progression Free Survival=time from date of inclusion to date of first documentation of progressive disease (death, biological progression, clinical progression). Biological progression: date of the first PSA increase after the nadir and greater than or equal to (≥) 4 ng/mL under treatment. Clinical progression: date of appearance of the clinical sign of progression under treatment. Clinical signs of progression are: 1. Appearance of marked increase of bone pain or appearance of symptoms related to disease progression (example: liver, lungs, kidneys); 2. Alteration of general health conditions related to disease progression (decrease of at least 2 degrees in the European Organization for Research and Treatment of Cancer (ECOG) performance status, weight loss of more than 10% since the last visit); 3. Anemia - drop in hemoglobin level of more than 2 gram per deciliter (g/dL) since the last visit (only if disease related).

  Randomization (Month 6) up to Week 396 after randomization

Secondary Outcomes (2)

• European Organization for research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) - C30

  Randomization (Month 6) up to Week 396 after randomization

• Change from Baseline in Subjective Clinical Efficacy (Symptomatic)

  Randomization (Month 6) up to Week 396 after randomization

Study Arms (2)

Continuous Therapy

ACTIVE COMPARATOR

Continuous complete androgen suppression therapy with leuprorelin 3.75 mg sustained release (SR), injection, subcutaneously once every 28 days and flutamide, 250 mg, tablet, orally thrice daily until there are signs of disease progression.

Drug: Leuprorelin; Drug: Flutamide

Intermittent therapy

EXPERIMENTAL

Intermittent complete androgen suppression therapy starting at randomization with interruption of treatment given in the induction period until PSA levels reach \>=10 ng/mL or other signs of progression appear. Upon treatment resumption, leuproreline 3.75 mg SR, injection, subcutaneously once every 28 days and flutamide 250 mg, tablet, orally thrice daily, until PSA levels are \<normal (that is, \<4 ng/mL) and no signs of disease progression appear. The intermittent therapy will be continued similarly until the study end or the appearance of signs of disease progression under treatment.

Drug: Leuprorelin; Drug: Flutamide

Interventions

Leuprorelin DRUG

Leuprorelin injection

Continuous Therapy; Intermittent therapy

Flutamide DRUG

Flutamide tablets

Continuous Therapy; Intermittent therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed metastatic cancer of the prostate (stage D2 or Tx Nx M1 ≠ M1a) with measurable bone or visceral (lung, liver, etc.) metastases (radiographic conformation was necessary in the event of a questionable bone scan detection in conjunction with only slightly elevated PSA levels \[at least 20 ng/mL or less than or equal to 50 ng/mL\]). The prostatic carcinoma could have been diagnosed at an earlier stage and treated without castration.
• Metastatic cancer of the prostate requiring first-line therapy.
• Pre-assessment PSA 5-fold or higher than the standard level set by the central laboratory, that is, PSA greater than or equal to (≥) 20 ng/mL as quantitated by the Hybritech radioimmunoassay (normal is less than \[\<\] 4 ng/mL).
• ECOG performance status of no more than 2.
• Normal testosterone levels according to the central laboratory standards.
• Aspartate transaminase (AST) and alanine transaminase (ALT) \< 2.25-fold higher than the standard levels set by the central laboratory (except when liver metastases were present).
• Anticipated life expectancy greater than 9 months.
• Subjects who meet the pre-assessment criteria and who has PSA \< 4 ng/mL after 6 months of induction therapy.

You may not qualify if:

• Subject refuse to sign the informed consent form or is likely to be uncooperative or not to comply with the obligations set out in the study protocol.
• Subject has received prior hormonal (and neoadjuvant) treatment prompting medical castration (estrogens, hormone-releasing hormone agonists, androgens) or has undergone surgical castration.
• Subject has undergone bilateral suprarenalectomy or hypophysectomy.
• Subject had another cancer (except basiloma) with the past 5 years.
• Subject has serious unstable progressive disease (renal, hepatic, cardiovascular, psychological, etc).
• Subjects who met the pre-assessment criteria and who, after 6 months of induction therapy, had PSA ≥ 4 ng/mL and/or on-treatment signs of disease progression.

Sponsors & Collaborators

• Takeda: lead

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Leuprolide; Flutamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Study Officials

• Nicolas MOTTET, MD

  Clinique Mutualiste de Saint-Etienne

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2009
• First Posted: January 6, 2009
• Study Start: December 1, 1996
• Primary Completion: September 1, 2005
• Study Completion: December 1, 2008
• Last Updated: July 29, 2015

Record last verified: 2015-07