Personalized Treatment Selection for Metastatic Breast Cancer

NCT00780676 | Terminated Phase 2 Results

• 2 other identifiers: 2007-0574NCI-2012-01671
• Study Type: interventional
• Target: 97
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to learn if researchers can use genetic tests to predict who may benefit from treatment with SprycelTM (dasatinib) or selumetinib (AZD6244).

Conditions

Breast Cancer

Keywords

Dasatinib; Metastatic Breast Cancer; Sprycel; BMS-354825; Genetic testing; AZD6244; Selumetinib

Outcome Measures

Primary Outcomes (1)

• Clinical Benefit (CB) Rate (CB = Participants With Objective Tumor Response or Stable Disease > 6 Months)

  Rate of participants with response complete, partial response or stable disease categorized by Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. Radiological response assessments must be repeated every 8 weeks during therapy.

  Tumor status assessed every 8 weeks during therapy, up to 6 months

Study Arms (4)

Dasatinib sensitivity signature

EXPERIMENTAL

Participants predicted to respond to Dasatinib (Sprycel) by predictive gene signature receive dasatinib 100 mg by mouth daily.

Drug: Dasatinib

SRC pathway activity signature

EXPERIMENTAL

Participants predicted to respond to Dasatinib (Sprycel) by predictive gene signature receive dasatinib 100 mg by mouth daily.

Drug: Dasatinib

Dasatinib target index

EXPERIMENTAL

Participants predicted to respond to Dasatinib (Sprycel) by predictive gene signature receive dasatinib 100 mg by mouth daily.

Drug: Dasatinib

Selumetinib pathway predictor

EXPERIMENTAL

Participants predicted to respond to selumetinib/AZD6244 by predictive gene signature (either MEK pathway activity predictor positive or MEK pathway predictor negative) receive selumetinib 75 mg by mouth twice daily (BID).

Drug: AZD6244

Interventions

Dasatinib DRUG

100 mg tablet by mouth daily

Also known as: Sprycel, BMS-354825

Dasatinib sensitivity signature; Dasatinib target index; SRC pathway activity signature

AZD6244 DRUG

75 mg by mouth twice daily.

Also known as: Selumetinib

Selumetinib pathway predictor

Eligibility Criteria

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

You may qualify if:

• Patients must have measurable or evaluable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
• Subject, age \> 18 years (the safety and efficacy of dasatinib and the appropriate dose has not been established for children).
• Signed written informed consent including a HIPAA form according to institutional guidelines.
• Performance status Zubrod scale 0-2 (Appendix B) within 8 days of starting therapy.
• Full physical examination and history including documentation of weight, height, and vital signs within 8 days of starting therapy.
• Patients may have received any number of previous therapies for metastatic breast cancer. Patients must have received, had a contraindication to, or declined treatment with an anthracycline and taxane (and Herceptin if HER-2 positive) in either the adjuvant or metastatic setting.
• Adequate organ function assessed within 14 days of study therapy, defined as: (a)Total bilirubin \</= 2.0 times the institutional Upper Limit of Normal (ULN); (b) Hepatic enzymes (AST, ALT ) \</= 2.5 times the institutional ULN; (c) Serum Na, K+, Mg2+, Phosphate and Ca2+ \>/= lower limit of normal (LLN); (d) Serum Creatinine \< 1.5 time the institutional ULN; and (e) Hemoglobin, Neutrophil count, Platelets, PT, PTT all Grade 0-1.
• A baseline EKG within 14 days of starting therapy, with a QTc interval not \> 460 msec in women, or \> 450 in men.
• Ability to take oral medication (dasatinib must be swallowed whole).
• Patient must agree to discontinue St. Johns Wort while receiving dasatinib therapy if previously taken.
• Patient must agree that IV bisphosphonate therapy will be withheld for the first 8 weeks of dasatinib therapy due to risk of hypocalcemia. (After the need for Ca2+ supplementation has been assessed and levels documented to be \>LLN, subjects on prior bisphosphonate may be restarted with caution at the investigator's discretion).
• Females of childbearing potential must have a negative serum pregnancy test within 7 days of starting therapy.
• Persons of reproductive potential must agree to use and utilize a barrier method of contraception throughout treatment and for at least 4 weeks after study drug is stopped.
• Concurrent medications must be assessed, and patient must agree to discontinue all restricted medications within 7 days of starting therapy.
• Stable brain metastasis for at least 3 months

You may not qualify if:

• Concurrent medical condition which may increase the risk of toxicity, including: (a) pleural or pericardial effusion of any grade; (b) uncontrolled angina, congestive heart failure or MI within (6 months); (c) history of congenital long QT syndrome or prolonged QTc interval on pre-entry electrocardiogram \> 460 msec in women and \>450 msec. in men; (d) any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes); continued in excl # 3
• CYP3A4 inhibitors. Dasatinib is primarily metabolized by the CYP3A4 enzyme. Therefore, potent inhibitors of CYP3A4 may increase dasatinib plasma concentrations: (i) ketoconazole, itraconazole, erythromycin, clarithromycin,ritonavir, atazanavir, indinavir, nefazodone, nelfinavir, saquinavir; (ii) telithromycin; and (iii) subjects should be advised not to consume substantial quantities of grapefruit juice.
• Medications which durably inhibit platelet function or inhibit anticoagulation. Medications which directly and durably inhibit platelet function or coagulation include: (i) aspirin or aspirin-containing combinations, clopidogrel, dipyridamole, tirofiban, dipyridamole, epoprostenol, eptifibatide, cilostazol, abciximab, ticlopidine, cilostazol; and (ii) warfarin, heparin/low molecular weight heparin \[e.g., danaparoid, dalteparin, tinzaparin, enoxaparin\]. Exceptions: low-dose warfarin for prophylaxis to prevent catheter thrombosis, and heparin for flushes of IV lines is allowed.
• Women who are unwilling or unable to use a barrier method of contraception to avoid pregnancy for the entire study period and for at least 4 weeks after cessation of study drug, or have a positive pregnancy test at baseline, or are pregnant or breast-feeding. Prior to study enrollment, women of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy.
• Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Bristol-Myers Squibb: collaborator
• AstraZeneca: collaborator

Study Sites (1)

UT MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Dasatinib; AZD 6244

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Limitations and Caveats

Study terminated according to early stopping rules.

Results Point of Contact

• Title: Stacy Moulder, MD/Associate Professor, Breast Medical Oncology
• Organization: University of Texas (UT) MD Anderson Cancer Center

CR_Study_Registration@mdanderson.org

713-792-2360

Study Officials

• Stacy Moulder, MD

  UT MD Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: October 24, 2008
• First Posted: October 28, 2008
• Study Start: June 1, 2009
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2014
• Last Updated: September 3, 2020
• Results First Posted: July 20, 2015

Record last verified: 2020-09

Locations

US (1)