NCT01197170

Brief Summary

The goal of this clinical research study to find the highest tolerated dose of anastrozole alone or in combination with either everolimus (Afinitor), sorafenib (Nexavar), erlotinib (Tarceva), fulvestrant (Faslodex), or bevacizumab (Avastin) that can be given to patients with advanced cancer. The safety of these drug combinations will also be studied.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
277

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Sep 2010

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 7, 2010

Completed
Same day until next milestone

Study Start

First participant enrolled

September 7, 2010

Completed
2 days until next milestone

First Posted

Study publicly available on registry

September 9, 2010

Completed
10.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 13, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 13, 2021

Completed
Last Updated

January 22, 2021

Status Verified

January 1, 2021

Enrollment Period

10.4 years

First QC Date

September 7, 2010

Last Update Submit

January 20, 2021

Conditions

Solid TumorsAdvanced Cancer

Keywords

Hormonal therapiesEstrogen receptorProgesterone receptorHormone blockadeHormone-positive tumorsAdvanced cancerMetastatic cancerAvastinAnti-VEGF monoclonal antibodyrhuMAB-VEGFAfinitorRAD001NexavarBAY43-9006OSI-774Tarceva

Outcome Measures

Primary Outcomes (1)

  • Maximum Tolerated Dose (MTD)

    MTD defined as highest dose at which no more than 1 of 6 evaluable patients has had a dose limiting toxicity (DLT). Six patients should be treated before the dose is declared as MTD. DLTs defined as adverse events (AEs) related to study agents which occurs during the first cycle of treatment.

    28 day cycle

Secondary Outcomes (1)

  • Tumor Response

    Every 21 or 28 days depending on study group

Study Arms (5)

Anastrozole

EXPERIMENTAL

1 mg PO (by mouth) daily for 28 days.

Drug: Anastrozole

Anastrozole + Bevacizumab

EXPERIMENTAL

Anastrozole 1 mg PO daily and Bevacizumab starting dose 10 mg IV Day 1 of 21 day cycle. Expansion group added when MTD dose of Anastrozole + Bevacizumab found.

Drug: AnastrozoleDrug: Bevacizumab

Anastrozole + Everolimus

EXPERIMENTAL

Anastrozole 1 mg PO daily and Everolimus starting dose 5 mg PO daily for 28 day cycle. Expansion group added when MTD dose of Anastrozole + Everolimus found.

Drug: AnastrozoleDrug: Everolimus

Anastrozole + Sorafenib

EXPERIMENTAL

Anastrozole 1 mg PO daily and Sorafenib starting dose 200 mg PO twice a day for 28 day cycle. Expansion group added when MTD dose of Anastrozole + Sorafenib found.

Drug: AnastrozoleDrug: Sorafenib

Anastrozole + Erlotinib

EXPERIMENTAL

Anastrozole 1 mg PO daily and Erlotinib starting dose 75 mg PO daily for 28 day cycle. Expansion group added when MTD dose of Anastrozole + Erlotinib found.

Drug: AnastrozoleDrug: Erlotinib

Interventions

AnastrozoleDRUG

1 mg by mouth daily of a 28 day cycle.

Also known as: Arimidex
AnastrozoleAnastrozole + BevacizumabAnastrozole + ErlotinibAnastrozole + EverolimusAnastrozole + Sorafenib
BevacizumabDRUG

Starting dose 10 mg by vein on day 1 of a 21 day cycle.

Also known as: Avastin, Anti-VEGF monoclonal antibody, rhuMAB-VEGF
Anastrozole + Bevacizumab
EverolimusDRUG

Starting dose 5 mg by mouth daily for a 28 day cycle.

Also known as: Afinitor, RAD001
Anastrozole + Everolimus
SorafenibDRUG

Starting dose 200 mg by mouth twice a day of a 28 day cycle.

Also known as: Nexavar, BAY43-9006
Anastrozole + Sorafenib
ErlotinibDRUG

Starting dose 75 mg by mouth daily for a 28 day cycle.

Also known as: OSI-774, Tarceva
Anastrozole + Erlotinib

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients with pathologically confirmed advanced or metastatic cancer that is refractory to standard therapy, relapsed after standard therapy, or who have had no standard therapy that induces a CR rate of at least 10% or improves survival by at least three months.
  • Measurable or non-measurable disease
  • Patients must have tumors that demonstrate ER/PR+ (positivity by IHC staining \>/= 1%).
  • At least 4 weeks since the last dose of chemotherapy, immunotherapy, surgery, or radiation therapy (Exception: patients may have received palliative low dose radiation therapy one week before treatment provided it is not given to the only targeted lesions); at least 6 weeks for therapy which is known to have delayed toxicity (nitrosoureas, mitomycin-C, and liposomal doxorubicin); at least 4 weeks (or 5 half-lives, whichever is shorter) since treatment with biologic/targeted therapies; at least 2 weeks since last hormonal therapy
  • Eastern Cooperative Oncology Group (ECOG) performance status 0,1, or 2
  • Patients must have normal organ and marrow function defined as: absolute neutrophil count \>/= 1,000/mL; platelets \>/= 50,000/mL; creatinine \</= 2 X ULN; total bilirubin \</= 2.0; ALT(SGPT) \</= 3 X ULN; Exception for patients with liver metastasis: total bilirubin \</= 3 x ULN; ALT(SGPT) \</= 5 X ULN.
  • Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 30 days after the last dose.
  • Ability to understand and the willingness to sign a written informed consent document
  • Female patients must either be: Post-menopausal women as defined by a. age \>/= 60 years of age; b. prior bilateral oophorectomy; c. age \< 60 with at least 12 months of spontaneous amenorrhea or post-menopausal range FSH and estradiol levels OR Premenopausal women receiving a gonadotropin-releasing hormone agonist.

You may not qualify if:

  • Patients with uncontrolled concurrent illness, including but not limited to: ongoing or active infection; altered mental status or psychiatric illness/social situations that would limit compliance with study requirements and/or obscure study results.
  • Uncontrolled systemic vascular hypertension (systolic blood pressure \> 140 mm Hg, diastolic blood pressure \> 90 mm Hg on medication).
  • Patients with clinically significant cardiovascular disease: history of CVA within 6 months, myocardial infarction or unstable angina within 6 months, or unstable angina pectoris.
  • Women who are pregnant or breastfeeding
  • Patients with a history of bone marrow transplant within the previous two years.
  • Patients with a known hypersensitivity to any of the components of the drug products.
  • Patients unable to swallow oral medications or with pre-existing gastrointestinal disorders that might interfere with proper absorption of oral drugs.
  • Patients with major surgery within 30 days prior to entering the study.
  • Age under 18 years.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

  • Wheler JJ, Moulder SL, Naing A, Janku F, Piha-Paul SA, Falchook GS, Zinner R, Tsimberidou AM, Fu S, Hong DS, Atkins JT, Yelensky R, Stephens PJ, Kurzrock R. Anastrozole and everolimus in advanced gynecologic and breast malignancies: activity and molecular alterations in the PI3K/AKT/mTOR pathway. Oncotarget. 2014 May 30;5(10):3029-38. doi: 10.18632/oncotarget.1799.

    PMID: 24912489DERIVED

Related Links

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

AnastrozoleBevacizumabEverolimusSorafenibErlotinib Hydrochloride

Condition Hierarchy (Ancestors)

Neoplastic ProcessesNeoplasmsPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

NitrilesOrganic ChemicalsTriazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsAntibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsSirolimusMacrolidesLactonesPhenylurea CompoundsUreaAmidesBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsNiacinamideNicotinic AcidsAcids, HeterocyclicPyridinesQuinazolinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-Ring

Study Officials

  • Filip Janku, MD, PHD

    M.D. Anderson Cancer Center

    PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

First Submitted

September 7, 2010

First Posted

September 9, 2010

Study Start

September 7, 2010

Primary Completion

January 13, 2021

Study Completion

January 13, 2021

Last Updated

January 22, 2021

Record last verified: 2021-01

Locations

US(1)