Phase II Trial of SAHA & Tamoxifen for Patients With Breast Cancer

NCT00365599 | Completed Phase 2 Results DMC

• 1 other identifier: MCC-14662
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 8

Brief Summary

Phase II trial to explore the efficacy of vorinostat and tamoxifen combined.

Conditions

Breast Cancer

Keywords

Breast cancer; Suberoylanilide hydroxamic acid (SAHA); Vorinostat; Tamoxifen; Anti-hormonal therapy; Estrogen receptor positive; Progesterone receptor positive; Metastatic disease; Aromatase inhibitors (Ais); Histone deacetylase (HDAC) inhibitors; Selective estrogen receptor modulators(SERMS)

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Objective Response (OR)

  The Objective Response Rate. Response and progression were evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST). Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are used in the RECIST criteria. For the purposes of this study, patients were evaluated for response every 8 weeks. In addition to a baseline scan, confirmatory scans were also obtained ≥ 4 weeks following initial documentation of objective response.

  24 weeks

Secondary Outcomes (2)

• Time to Progression (TTP)

  Up to 30 months

• Number of Participants With Serious Adverse Events (SAEs)

  4 years, 7 months

Study Arms (1)

Vorinostat and Tamoxifen

EXPERIMENTAL

As outlined in Intervention descriptions

Drug: suberoylanilide hydroxamic acid (SAHA, Vorinostat); Drug: tamoxifen citrate (Tamoxifen)

Interventions

suberoylanilide hydroxamic acid (SAHA, Vorinostat) DRUG

Vorinostat will be used to potentiate the effects of tamoxifen or overcome tamoxifen resistance. All patients will receive vorinostat at 400 mg by mouth (po) daily for 3 out of 4 weeks. Responses will be assessed after 2 cycles (8 weeks + 4 days).

Also known as: SAHA, Vorinostat, NSC #701852

Vorinostat and Tamoxifen

tamoxifen citrate (Tamoxifen) DRUG

Tamoxifen will be given once daily at 20 mg. Tamoxifen will be given continuously. Responses will be assessed after 2 cycles (8 weeks + 4 days).

Also known as: Nolvadex, Tam, Tamoxifen

Vorinostat and Tamoxifen

Eligibility Criteria

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

You may qualify if:

• Patients must have cytologically/histologically documented locally advanced or metastatic breast cancer with either:
• Progression on treatment with any aromatase inhibitor for metastatic disease;
• Recurrence while on adjuvant aromatase inhibitors or within 12 months of completion;
• Recurrence after having completed adjuvant tamoxifen for at least 12 months;
• Patient who are not candidates for or are intolerant of aromatase inhibitor treatment;
• Patients are allowed (but not required) to have one prior chemotherapy regimen for metastatic disease.
• Tumors must express estrogen or progesterone receptor.
• Patients are eligible regardless of the menopausal status.
• Age \> 18 years old
• Patients must have Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Patients must be able to give informed consent and able to follow guidelines given in the study.
• Patients must have acceptable organ function, as defined by the following laboratory parameters: white blood count (WBC) \>3.0 x 10\^9/L; absolute neutrophil count (ANC) \>1.5 x 10\^9/L; hemoglobin (Hgb) \>10.0g/dL; platelets (PLT) \>100 x 10\^9/L, Bilirubin \< 2.0 mg/dl, aspartate aminotransferase/alanine aminotransferase (AST/ALT) \< 2.5 X upper limit of normal (ULN), Creatinine \<1.8 mg/dl (Creatinine clearance \>60 ml/min).
• Women of childbearing age must have a negative pregnancy test. All patients of reproductive potential must use an effective method of contraception during the study and 6 months following termination of treatment. (Not applicable to patients with bilateral oophorectomy and/or hysterectomy or to female patients who are older than 50 years and have not had a menstrual cycle in more than one year.
• Patients must have measurable disease by RECIST criteria by staging studies performed within 30 days of enrollment. For patients with bone only disease: For this protocol isolated bone lesions can be classified as target lesions if they are measurable by MRI at screening and must be followed by MRI.
• Both men and women of all races and ethnic groups are eligible for this trial.

You may not qualify if:

• Patients must not have received tamoxifen for metastatic disease.
• Patients must not have evidence of significant active infection (e.g., pneumonia, cellulitis, wound abscess, etc.) at time of study entry.
• Patients must be disease-free of prior invasive malignancies for \> 5 years with the exception of: curatively-treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix.
• Pregnant and breast-feeding women are excluded from the study because effects on the fetus are unknown and there may be a risk of increased fetal wastage.
• Patients with uncontrolled central nervous system (CNS) metastasis or a history of seizures are excluded. Patients with stable CNS metastasis (either surgically resected, treated with gamma knife or stable for 3 months following whole brain radiation therapy \[WBRT\] are eligible). Patients with stable brain metastases will need an MRI within 4 weeks prior to start of therapy.
• Patients may not be receiving any other investigational agents and must have stopped all other histone deacetylase inhibitors (including Valproic acid) or other hormonal therapies.
• Patients must have discontinued their prior therapies for breast cancer and radiation therapy for a minimum of 3 weeks, patient is excluded if radiation therapy was given to a single measurable lesion and the disease is otherwise not measurable.
• Patients are excluded if they have any known hypersensitivity reaction to tamoxifen.
• Patient with a history of blood clots are not eligible.
• Women who have abnormal vaginal bleeding and/or endometrial hyperplasia or cancer are not eligible.
• Patients with evidence of visceral crisis are not eligible for this study.

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (8)

University of California

San Francisco, California, 94143, United States

Location

Bethesda Memorial Hospital Research Center

Boynton Beach, Florida, 33435, United States

Location

M.D. Anderson of Orlando

Orlando, Florida, 32806, United States

Location

Fawcett Memorial Hospital

Port Charlotte, Florida, 33949, United States

Location

Martin Memorial Cancer Center

Stuart, Florida, 34994, United States

Location

Tallahassee Memorial HealthCare, Inc.

Tallahassee, Florida, 32308, United States

Location

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612, United States

Location

St. Joseph's/Candler

Savannah, Georgia, 31405, United States

Location

Related Links

• Moffitt Cancer Center Clinical Trials Website

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis; Bulbo-Spinal Atrophy, X-Linked

Interventions

Vorinostat; Tamoxifen

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Muscular Atrophy, Spinal; Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Motor Neuron Disease; Neuromuscular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Results Point of Contact

• Title: Susan Minton, D.O.
• Organization: H. Lee Moffitt Cancer Center and Research Institute

susan.minton@moffitt.org

813-745-3806

Study Officials

• Susan Minton, D.O.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 15, 2006
• First Posted: August 17, 2006
• Study Start: February 1, 2006
• Primary Completion: April 1, 2011
• Study Completion: August 1, 2012
• Last Updated: November 21, 2014
• Results First Posted: March 26, 2012

Record last verified: 2014-11

Locations

US (8)