Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Musculoskeletal Diseases

Nutritional and Metabolic Diseases

Prostatic Neoplasms

Osteoporosis

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Bone Diseases

Bone Diseases, Metabolic

Metabolic Diseases

All Drugs and Chemicals

Bone Density Conservation Agents

Micronutrients

Gastrointestinal Agents

Channel Blockers

Vitamins

Androgens

Estrogens, Conjugated (USP)

Estrogens

Vitamin D

Cholecalciferol

Calcium

Calcium Carbonate

Calcium, Dietary

Risedronic Acid

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Trace Elements

Hormone Antagonists

Antacids

Anti-Ulcer Agents

Calcium Channel Blockers

Vitamin D3

Calciferol

Patients receive oral calcium, oral cholecalciferol, oral risedronate placebo, and oral estrogen placebo daily.

Treatment in all arms continues for 2 years.

Quality of life is assessed at baseline, monthly for 6 months, and then at 1 and 2 years.

Bone mineral density is assessed at baseline, 6 months, and 1 and 2 years.

Patients receive oral calcium, oral cholecalciferol, oral risedronate, and oral estrogen placebo daily.

Treatment in all arms continues for 2 years.

Quality of life is assessed at baseline, monthly for 6 months, and then at 1 and 2 years.

Bone mineral density is assessed at baseline, 6 months, and 1 and 2 years.

Patients receive oral calcium, oral cholecalciferol, low-dose oral conjugated estrogens, and oral risedronate placebo daily.

Treatment in all arms continues for 2 years.

Quality of life is assessed at baseline, monthly for 6 months, and then at 1 and 2 years.

Bone mineral density is assessed at baseline, 6 months, and 1 and 2 years.

Patients receive oral calcium, oral cholecalciferol, low-dose oral conjugated estrogens, and oral risedronate daily.

Treatment in all arms continues for 2 years.

Quality of life is assessed at baseline, monthly for 6 months, and then at 1 and 2 years.

Bone mineral density is assessed at baseline, 6 months, and 1 and 2 years.

calcium carbonate

cholecalciferol

risedronate sodium

placebo

Charles L. Loprinzi, MD

RATIONALE: Preventing bone loss in patients who are undergoing androgen ablation for prostate cancer may decrease the risk of fractures and may help patients live more comfortably. It is not yet known whether calcium is more effective with or without estrogen and/or risedronate in preventing osteoporosis.

PURPOSE: Randomized phase III trial to compare the effectiveness of two forms of calcium with or without estrogen and/or risedronate in preventing osteoporosis in patients with prostate cancer who are receiving androgen ablation therapy.

OBJECTIVES:

* Compare the change in bone mineral density in patients with prostate cancer who are receiving androgen-ablation therapy treated with calcium and cholecalciferol with or without conjugated estrogens and with or without risedronate.
* Compare the toxicity of these regimens in these patients.
* Compare the changes in bone markers in patients treated with these regimens.
* Compare the quality of life of patients treated with these regimens.
* Compare hot flashes in patients treated with these regimens.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to duration of therapy with luteinizing hormone-releasing hormone agonists (no more than 30 days vs 31 to 150 days vs 151 to 365 days vs more than 365 days). Patients are randomized to 1 of 4 treatment arms.

* Arm I: Patients receive oral calcium, oral cholecalciferol, oral risedronate placebo, and oral estrogen placebo daily.
* Arm II: Patients receive oral calcium, oral cholecalciferol, oral risedronate, and oral estrogen placebo daily.
* Arm III: Patients receive oral calcium, oral cholecalciferol, low-dose oral conjugated estrogens, and oral risedronate placebo daily.
* Arm IV: Patients receive oral calcium, oral cholecalciferol, low-dose oral conjugated estrogens, and oral risedronate daily.

Treatment in all arms continues for 2 years.

Quality of life is assessed at baseline, monthly for 6 months, and then at 1 and 2 years.

Bone mineral density is assessed at baseline, 6 months, and 1 and 2 years.

PROJECTED ACCRUAL: A total of 282 patients (70 per treatment arm) will be accrued for this study within 14 months.

Calcium With or Without Estrogen and/or Risedronate in Preventing Osteoporosis in Patients With Prostate Cancer

Osteoporosis Prevention in Prostate Cancer Patients Receiving Androgen Ablation Therapy: A Phase III Randomized, Placebo-Controlled, Double-Blind Study

National Cancer Institute (NCI)

Alliance for Clinical Trials in Oncology

Skin and Connective Tissue Diseases

Gland and Hormone Related Diseases

Rare Diseases

Uterine Cervical Neoplasms

Carcinoma

Breast Neoplasms

Carcinoma, Squamous Cell

Head and Neck Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Breast Diseases

Skin Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Antineoplastic Agents

Fulvestrant

Antineoplastic Agents, Hormonal

* Cohort A0: Advanced Solid tumors expressing PI3Kα mutations.
* Cohort A1: HR+/HER2- breast cancer expressing PI3Kα H1047X mutations or other kinase domain mutations.

* Cohort A2: Gynecologic cancers
* Cohort A3: HNSCC
* Cohort A4: Other solid tumors not included in Cohorts A0, A1, or A2
* Mutations for Cohorts A2, A3, and A4: PI3Kα H1047X mutations or other kinase domain mutations
* Cohort A5: Solid tumors expressing PI3Kα helical domain mutations (E542/E545)

Recommended Phase 2 dose (RP2D)

Cohort A1: HR+/HER2- breast cancer expressing PI3Kα H1047X mutations or other kinase domain mutations.

Cohort A1: HR+/HER2- breast cancer expressing PI3Kα H1047X mutations or other kinase domain mutations.

Cohort B: HR+/HER2- breast cancer expressing PI3Kα H1047X mutations or other kinase domain mutations.

STX-478 is a second generation, mutant-selective, oral PI3Kα small molecule allosteric inhibitor.

STX-478

Fulvestrant will be administered according to local labeling.

For questions concerning enrollment

Mark Chao, MD, PhD

Study STX-478-101 is a multipart, open-label, phase 1/2 study evaluating the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of STX-478 in participants with advanced solid tumors with certain mutations.

Part 1 will evaluate STX-478 as monotherapy in participants with advanced solid tumors and breast cancer; Part 2 will evaluate STX-478 therapy as combination therapy with fulvestrant in participants with breast cancer.

Each study part will include a 28-day screening period, followed by treatment with STX-478 monotherapy or combination therapy.

First-in-Human Study of STX-478 as Monotherapy and in Combination With Other Antineoplastic Agents in Participants With Advanced Solid Tumors

First-in-Human Study of STX-478, a Mutant-Selective PI3Kα Inhibitor as Monotherapy and in Combination With Other Antineoplastic Agents in Participants With Advanced Solid Tumors

Scorpion Therapeutics, Inc.

Symptoms and General Pathology

Recurrence

Tamoxifen

Estrogen Receptor Modulators

Selective Estrogen Receptor Modulators

The active study group consists of 50 year or older postmenopausal women taking tamoxifen for the prevention of reoccurrence of breast cancer, do not meet exclusion criteria, meet all inclusion criteria, and are enrolled members for Medco clients agreeing to participate.

If the patient's CYP2D6 metabolism status is 'poor' then specialist pharmacist will discuss drug therapy alternatives to tamoxifen.

Poor Metabolism Status Follow Up Therapy Considerations

If the patient after having a CYP2D6 test has any drugs that inhibit tamoxifen metabolism then specialist pharmacist will contact the physician for alternative drug therapies.

CYP2D6 Inhibiting Drugs

Robert Epstein, MD, MS

This study will assess the impact of CYP450 2D6 genotype pharmacogenetic testing and the corresponding prescribing impact for postmenopausal women using tamoxifen in a patient care setting for prevention of recurrent breast cancer.

Tamoxifen is a non-steroidal hormonal drug with weak estrogen agonist and potent estrogen antagonist actions. The liver CYP450 metabolic enzyme systems are responsible for metabolizing tamoxifen (the pro-drug form) into its active metabolites. A secondary tamoxifen metabolite known specifically as 4-hydroxy-N-desmethyl-tamoxifen or endoxifen is recognized as the principal potent metabolite responsible for tamoxifen suppression of estrogen-dependent cell proliferation, the stimulus for breast tumor growth. Biotransformation to endoxifen is through the CYPP450 2D6 pathway; therefore, the ability of tamoxifen to effectively suppress breast cancer is jeopardized in patients with certain CYP450 2D6 genetic variants and/or those receiving drug therapy that are known to alter CYP450 2D6 function (i.e., with CYP450 2D6 inhibitors).

Four phenotype expressions classified as ultrarapid, extensive, intermediate and poor metabolizers can be discerned from genotype testing for CYP450 2D6 activity. Patients with normal metabolic activity are known as extensive metabolizers given that they possess either two (genotype = wt/wt) or one (genotype = wt/vt) functioning CYP450 2D6 gene that converts a sufficient amount of tamoxifen in to its active form. Intermediate metabolizers have at least some or very low CYP450 2D6 activity and there does not appear to be uniform consensus on the impact of this phenotype on tamoxifen drug disposition. Poor metabolizers lack any functional CYP450 2D6 activity, and therefore, they do not metabolize tamoxifen enough to produce sufficient endoxifen activity. Approximately 10% of patients (7% of Caucasians and 1-3% of other ethnic groups) are poor metabolizers with a complete absence of CYP450 2D6 activity.

The genetic variants associated with diminished or absent CYP450 2D6 activity are found on CYP450 2D6 alleles \*3, \*4, \*5, \*6 and \*10. The \*3, \*4, \*5 and \*6 alleles, when present in variant form (genotype = vt/vt), account for approximately 97% of nonfunctional CYP450 2D6 variants in caucasians. Of these mutations, those in CYP450 2D6 \*4 are most significant for endoxifen.

Poor metabolizer phenotype has been associated with worse relapse-free breast cancer survival and increased risk (up to three times that of intermediate metabolizer status who have some CYP450 2D6 activity) for breast cancer recurrence.

Diagnostic technology now exists to aid in determining which tamoxifen patients are potentially receiving suboptimal treatment from existing alterations in one or more of the approximately 80 alleles of the gene coding for the CPYP450 2D6 enzyme. Recognition of this phenomenon provides physicians and their patients the opportunity for considering the use of other anti-estrogen drugs such as aromatase inhibitors in women whose CYP450 2D6 phenotype puts them at risk for poor response to tamoxifen therapy.

This study will use this diagnostic technology to determine a patient's phenotype provide additional clinical information and alternative drug therapies to the patient's physician.

The Clinical and Economic Impact of Pharmacogenomic Testing for Tamoxifen Metabolism in Postmenopausal Women Receiving Tamoxifen for Prevention of Recurrent Breast Cancer

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Calcium With or Without Estrogen and/or Risedronate in Preventing Osteoporosis in Patients With Prostate Cancer	NCT00043069	Osteoporosis Prostate Cancer	calcium carbona... cholecalciferol Estrogen Antago... risedronate sod... placebo	18 Years -	Alliance for Clinical Trials in Oncology
First-in-Human Study of STX-478 as Monotherapy and in Combination With Other Antineoplastic Agents in Participants With Advanced Solid Tumors	NCT05768139	Breast Cancer Gynecologic Can... HNSCC Solid Tumors, A...	STX-478 Fulvestrant	18 Years -	Scorpion Therapeutics, Inc.
The Clinical and Economic Impact of Pharmacogenomic Testing for Tamoxifen Metabolism in Postmenopausal Women Receiving Tamoxifen for Prevention of Recurrent Breast Cancer	NCT00830973	Breast Neoplasm... Tamoxifen	Poor Metabolism... CYP2D6 Inhibiti...	50 Years -	Medco Health Solutions, Inc.
Calcium With or Without Estrogen and/or Risedronate in Preventing Osteoporosis in Patients With Prostate Cancer	NCT00043069	Osteoporosis Prostate Cancer	calcium carbona... cholecalciferol Estrogen Antago... risedronate sod... placebo	18 Years -	Alliance for Clinical Trials in Oncology

Spots Global Cancer Trial Database for estrogen antagonists