Liposomal Doxorubicin Before Mastectomy in Treating Women With Invasive Breast Cancer

NCT00290732 | Completed Phase 1 Results

• 3 other identifiers: J0503 CDR0000459502P30CA006973JHOC-J0503
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as liposomal doxorubicin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving chemotherapy in different ways, such as into the breast ducts, may kill more tumor cells. Giving chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. PURPOSE: This phase I trial is studying the side effects and best dose of liposomal doxorubicin when given before mastectomy in treating women with invasive breast cancer.

Conditions

Breast Cancer

Keywords

stage I breast cancer; stage II breast cancer; stage IIIA breast cancer; stage IIIC breast cancer; stage IV breast cancer; breast cancer in situ; ductal breast carcinoma in situ

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD)

  Maximum tolerated dose (MTD) of administering pegylated liposomal doxorubicin (PLD) into one duct of women with breast cancer awaiting mastectomy. MTD reflects highest dose of drug that did not cause Dose Limiting Toxicity (DLT) in more than 30% of patients.

  Until up to 30 days after PLD administration

Secondary Outcomes (2)

• Concentrations of Doxorubicin in Blood (Plasma) at Definitive Surgery

  Baseline, 4 hrs, day2/24 hrs, day 8, day of surgery/biopsy

• Concentrations of Doxorubicin in Tissue at Definitive Surgery

  Day of surgery/biopsy

Study Arms (2)

Intraductal arm

EXPERIMENTAL

Participants received intraductal administration of dextrose or dextrose with pegylated liposomal doxorubicin hydrochloride (or PLD) prior to conventional surgery for breast cancer.

Drug: Intraductal arm

Intravenous arm

ACTIVE COMPARATOR

Participants receiving standard intravenous administration of pegylated liposomal doxorubicin prior to breast biopsy for drug concentrations.

Drug: Intravenous arm

Interventions

Intraductal arm DRUG

Patients will receive PLD intraductally according to the dose escalation schema (Dose Level -1=1 mg, Dose Level 1=2 mg, Dose Level 2= 5mg, Dose Level 3=10 mg). The PLD dose will be diluted in 5% dextrose in water and will be mixed for a total volume of 5 ml. The PLD will be administered via a breast duct (i.e., intraductally) using a microcatheter

Also known as: Doxorubicin HCl Liposome Injection, Dox-SL, Doxil TM

Intraductal arm

Intravenous arm DRUG

Blood samples and a breast tissue biopsy collected to look at levels of doxorubincol from patients receiving intravenous pegylated liposomal doxorubin to compare to the group receiving drug intraductally.

Also known as: Doxorubicin HCl Liposome Injection, Dox-SL, Doxil TM

Intravenous arm

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Histologically confirmed infiltrating carcinoma of the breast meeting any of the following criteria: * T1-3, any N disease * Proven ductal carcinoma in situ * Unresected disease * Planned mastectomy as definitive surgical procedure * Known or suspected metastatic disease allowed provided mastectomy is planned * Nonpalpable tumor allowed (e.g., initial T2-3 tumor that responded to preoperative therapy) * No inflammatory breast cancer or other T4 features * Successful baseline ductogram * Baseline nipple aspiration procedure must identify a duct productive of nipple aspirate fluid * No severe nipple retraction * Hormone receptor status not specified PATIENT CHARACTERISTICS: * Female patients * Menopausal status not specified * ECOG performance status 0-2 * Absolute neutrophil count ≥1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Hemoglobin ≥ 9.0 g/dL * Creatinine ≤ 2 times upper limit of normal (ULN) * Bilirubin ≤ 2 times ULN * AST and ALT ≤ 2.5 times ULN * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No significant history of severe allergy to iodinated contrast material or debilitating anxiety that may not allow for a ductogram PRIOR CONCURRENT THERAPY: * See Disease Characteristics * Prior preoperative chemotherapy, trastuzumab (Herceptin®), or hormonal therapy allowed provided it was completed 7-14 days prior to study treatment * No prior radiation therapy, excisional biopsy, breast reduction, areolar surgery, or breast implant (present or past history of implant that was removed) * No other prior procedure that may have altered the breast ductal system in the ipsilateral breast * No other concurrent chemotherapy, radiotherapy, endocrine therapy, or biologic agents for breast cancer * No other concurrent investigational drugs * Concurrent bisphosphonates allowed

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202-5289, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231-2410, United States

Location

Related Publications (1)

• Stearns V, Mori T, Jacobs LK, Khouri NF, Gabrielson E, Yoshida T, Kominsky SL, Huso DL, Jeter S, Powers P, Tarpinian K, Brown RJ, Lange JR, Rudek MA, Zhang Z, Tsangaris TN, Sukumar S. Preclinical and clinical evaluation of intraductally administered agents in early breast cancer. Sci Transl Med. 2011 Oct 26;3(106):106ra108. doi: 10.1126/scitranslmed.3002368.

  PMID: 22030751 RESULT

MeSH Terms

Conditions

Breast Neoplasms; Breast Carcinoma In Situ; Carcinoma, Intraductal, Noninfiltrating

Interventions

liposomal doxorubicin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma in Situ; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Adenocarcinoma; Neoplasms, Ductal, Lobular, and Medullary

Limitations and Caveats

Duct cannulation was not successful in all participants; possibly due to extensive disease or prior excisional biopsy (2 subjects).

Results Point of Contact

• Title: Dr. Vered Stearns
• Organization: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

vstearn1@jhmi.edu

4432876489

Study Officials

• Vered Stearns, MD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  STUDY CHAIR

Publication Agreements

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

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: February 9, 2006
• First Posted: February 13, 2006
• Study Start: November 1, 2005
• Primary Completion: May 1, 2011
• Study Completion: October 1, 2011
• Last Updated: October 31, 2013
• Results First Posted: September 26, 2013

Record last verified: 2013-10

Locations

US (2)