Trial of Fulvestrant, MK-0646, and Dasatinib for Metastatic Hormone Receptor-Positive HER2-Negative Breast Cancer

NCT00903006 | Terminated Phase 1 Results DMC

• 1 other identifier: 2008-0336
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

The goals of this clinical research study are to learn the tolerable and effective doses of the drug MK-0646 that can be given in combination with Sprycel (dasatinib) and Faslodex (fulvestrant) to patients with hormone receptor-positive metastatic breast cancer. The safety of these drugs will be studied as well as markers in the tumors that may help researchers predict the tumors' reaction to the treatment.

Conditions

Breast Cancer

Keywords

Breast; Hormone receptor-positive metastatic breast cancer; Fulvestrant; Faslodex; MK-0646; Dasatinib; BMS-354825; Sprycel; Adjuvant hormonal therapy

Outcome Measures

Primary Outcomes (2)

• Phase I Maximum Tolerated Dose (MTD) for Dose Level 1

  Maximum Tolerated Dose (MTD) defined as the dose or dose-combination that has the mean posterior toxicity rate closest to the target toxicity rate of 0.33. Dose levels reviewed with each 28 day cycle. Treatment dose levels: Fulvestrant will be given using a loading dose of 500 mg intramuscularly (IM) on day 1 as two 250 mg/5 ml injections, followed by 500 mg IM on day 15 and on day 1 of each subsequent 28- day (+/- 2 days) cycle. MK-0646 will be given intravenously on days 1,8, 15, and 22 for each cycle at one of the two dose levels: 1) 5 mg/kg or 2) 10 mg/kg (Dose level 1) Dasatinib will be given orally (PO) continuously on days 1 -28 for each cycle at one of two dose levels: 1) 70 mg po daily or 2) 100 mg po daily

  28 day cycle

• Patient Response (+ Time to Disease Progression)

  Baseline, after two 28 day cycles, until disease progression.

Study Arms (4)

Group 1: Fulvestrant

ACTIVE COMPARATOR

Group 1 will receive Fulvestrant only.

Drug: Fulvestrant

Group 2: Fulvestrant + Dasatinib

ACTIVE COMPARATOR

Group 2 will receive Fulvestrant and Dasatinib.

Drug: Fulvestrant; Drug: Dasatinib

Group 3: Fulvestrant + MK-0646

ACTIVE COMPARATOR

Group 3 will receive Fulvestrant and MK-0646.

Drug: Fulvestrant; Drug: MK-0646

Group 4: Fulvestrant, MK-0646 + Dasatinib

ACTIVE COMPARATOR

Group 4 will receive Fulvestrant, MK-0646, and Dasatinib.

Drug: Fulvestrant; Drug: MK-0646; Drug: Dasatinib

Interventions

Fulvestrant DRUG

Starting dose of 500 mg through a needle into muscle on Days 1 and 15 of Cycle 1 and on Day 1 of Cycles 2 and beyond. On Day 1 of Cycle 1, injections into 2 different muscles, all other times one injection.

Also known as: Faslodex

Group 1: Fulvestrant; Group 2: Fulvestrant + Dasatinib; Group 3: Fulvestrant + MK-0646; Group 4: Fulvestrant, MK-0646 + Dasatinib

MK-0646 DRUG

Group 3 or Group 4, receive starting dose of 5 mg/kg by vein on Days 1, 18, 15, and 22 of every cycle.

Group 3: Fulvestrant + MK-0646; Group 4: Fulvestrant, MK-0646 + Dasatinib

Dasatinib DRUG

Group 2 or Group 4, starting dose of 70 mg (capsules) by mouth daily.

Also known as: BMS-354825, Sprycel

Group 2: Fulvestrant + Dasatinib; Group 4: Fulvestrant, MK-0646 + Dasatinib

Eligibility Criteria

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

You may qualify if:

• For the Phase I: Patients with histologically or cytologically confirmed diagnosis of metastatic hormone receptor-positive HER2-negative breast cancer who have received up to one line of endocrine therapy for metastatic disease.
• Measurable disease by Response Evaluation Criteria In Solid Tumors (RECIST) or evaluable disease (e.g., bone metastasis, or lesions which do not fulfill RECIST criteria for metastatic disease)
• Age \>/= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status of \</= 2
• Required laboratory values: Absolute neutrophil count (ANC)\>/= 1500 cells/mm\^3, platelet count \>/= 100,000 cells/mm\^3, hemoglobin \>/= 9 gm/L; bilirubin \</= 1.5 \* upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \</= 2.5 \* ULN; serum creatinine \</= 2.0 \* ULN
• Ability to understand the requirements of the study, provided written informed consent and authorization of use and disclosure of protected health information, and agree to abide by the study restrictions and to return for the required assessments.
• Patients must be postmenopausal (\> 12 months of amenorrhea, bilateral oophorectomy).
• Patients must have received prior anti-estrogen therapy in the adjuvant setting.
• Patients may have easily accessible tumors for biopsy (confirmed by interventional radiology).
• Patients must consent to biopsies.
• For the Phase II: Patients with histologically or cytologically confirmed diagnosis of metastatic hormone receptor-positive, HER2-negative, breast cancer who have received up to one line of endocrine therapy for metastatic disease.
• Measurable disease by RECIST or evaluable disease (e.g., bone metastasis, or lesions which do not fulfill RECIST criteria for metastatic disease)
• Age \>/= 18 years
• ECOG performance status of \</= 2
• Required Laboratory Values: ANC \>/= 1500 cells/mm\^3, platelet count \>/= 100,000 cells/mm\^3, hemoglobin \>/= 9 gm/L, Bilirubin \</= 1.5 \* ULN, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \</= 2.5 \* ULN

You may not qualify if:

• For the Phase I: History of prior malignancies within the past 5 years with the exception of curatively treated basal or squamous cell carcinomas of the skin or carcinoma in situ of the cervix
• Concurrent severe or uncontrolled medical disease (i.e., systemic infection, diabetes, hypertension, coronary artery disease, congestive heart failure, ongoing or recent gastrointestinal bleed, hepatic or cardiac compromise, hypocalcemia, or known platelet function abnormality).
• Concomitant medication known to prolong QT interval, unless discontinued \>/= 7 days of starting dasatinib therapy.
• Newly diagnosed (within 3 months before enrollment) or poorly controlled (defined as a fasting serum glucose \> 160 mg/dl or hemoglobin A1c \> 8% at screening), type 1 or 2 diabetes mellitus.
• Active or untreated brain metastasis
• Pleural or pericardial effusion of any grade
• Bone only metastases
• Patients for whom endocrine therapy is not appropriate (i.e. life threatening metastatic disease).
• Patients requiring therapeutic anticoagulation (Warfarin 1 mg for port maintenance is allowed).
• For the Phase II: History of prior malignancies within the past 5 years with the exception of curatively treated basal or squamous cell carcinomas of the skin or carcinoma in situ of the cervix
• Concurrent severe or uncontrolled medical disease (i.e., systemic infection, diabetes, hypertension, coronary artery disease, congestive heart failure, ongoing or recent gastrointestinal bleed, hepatic or cardiac compromise, hypocalcemia, or known platelet function abnormality).
• Concomitant medication known to prolong QT interval, unless discontinued \>/= 7 days of starting dasatinib therapy.
• Newly diagnosed (within 3 months before enrollment) or poorly controlled (defined as a fasting serum glucose \> 160 mg/dl or hemoglobin A1c \> 8% at screening), type 1 or 2 diabetes mellitus.
• Active or untreated brain metastasis
• Pleural or pericardial effusion of any grade

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Bristol-Myers Squibb: collaborator
• Merck Sharp & Dohme LLC: collaborator
• Commonwealth Foundation for Cancer Research: collaborator

Study Sites (1)

UT MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• UT MD Anderson Cancer Center website

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Fulvestrant; dalotuzumab; Dasatinib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Limitations and Caveats

Study terminated early due to small sample size.

Results Point of Contact

• Title: Ana Gonzalez-Angulo, MD / Associate Professor, Breast Medical Oncology
• Organization: University of Texas MD Anderson Cancer Center

CR_Study_Registration@mdanderson.org

713-792-2817

Study Officials

• Ana Gonzalez-Angulo, MD, MS

  UT MD Anderson Cancer Center

  STUDY CHAIR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2009
• First Posted: May 15, 2009
• Study Start: November 1, 2009
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2013
• Last Updated: February 2, 2015
• Results First Posted: February 2, 2015

Record last verified: 2014-06

Locations

US (1)