'ADVANCE' (A Pilot Trial)

'ADVANCE' (A Pilot Trial) ADjuVANt Chemotherapy in the Elderly: Developing and Evaluating Lower-Toxicity Chemotherapy Options for Older Patients With Breast Cancer

This study is being conducted to carefully study how chemotherapy is tolerated in group of patients age 70.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Paclitaxel; Drug: Carboplatin; Drug: Cyclophosphamide

Detailed Description

This clinical trial is dedicated to patients age 70 and older and is focused on understanding how the investigators can improve upon breast cancer outcomes for older women, a group of patients who often do worse than younger patients and who are not well represented in clinical trials to date. Through this clinical trial, the investigators aim to better understand the side effects, experiences, and changes in physical function that may occur with chemotherapy. The investigators are also very interested in the genomics (or gene-changes) and biological changes that may occur in breast cancers in older women that may be different from the changes we see in younger patients.

Even though the chemotherapy agents being used in this study are used frequently when treating breast cancer, The investigators have limited information on how these agents are tolerated in older patients. This research study is called a Feasibility Study, because the investigators will be closely monitoring how easily it is to administer chemotherapy to a relatively small group of participants (up to 40) and to what degree side effects occur. The investigators will administer commercially available chemotherapy agents used in breast cancer in the specific setting of the treating older patients with early-stage breast cancer and with some mild modification of how these agents are given and in what combination.

For participants with triple negative breast cancer, paclitaxel and carboplatin will be administered in standard, weekly doses. Both agents are FDA-approved for use in early breast cancer. However, carboplatin and paclitaxel are not typically used as a 'stand-alone' treatment for breast cancer, meaning they are often used together along with other chemotherapy agent(s) over a longer period.

For participants with hormone receptor-positive breast cancer, paclitaxel and cyclophosphamide will be administered, which are both FDA-approved agents to treat breast cancer as part of a longer regimen to treat early breast cancer. In this clinical trial the investigators are modifying the way the chemotherapy is delivered so that it may be more tolerable than the longer treatment course. This clinical trial does not limit the use of other chemotherapy or other treatments being recommended for breast cancer, but any other recommended treatments would be given after the participants receive their paclitaxel and carboplatin on the clinical trial.

• Study Type: Interventional
• Enrollment (Estimated): 41
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope National Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02115
      • Dana Farber Cancer Institute
    • Milford, Massachusetts, United States, 01757
      • Dana-Farber/Brigham and Women's Cancer Center (DF/BWCC) at Milford Regional Medical Center
    • South Weymouth, Massachusetts, United States, 02190
      • Dana-Farber/Brigham and Women's Cancer Center (DF/BWCC) in clinical affiliation with South Shore Hospital
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • Novant Health Oncology Specialists

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 70 years and older (Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants must have histologically or cytologically confirmed breast cancer that is human epidermal growth factor receptor 2 negative (HER2-negative) per the most recent 2018 ASCO CAP guidelines94
• Estrogen Receptor and Progesterone immunohistochemistry (IHC) status must be known; any status is eligible, but this will define in which cohort a patient will enroll:
• Additional eligibility for cohort 1: Triple negative disease- defined as IHC staining of <10% for ER and PR per local pathology review
• Additional eligibility for cohort 2: Hormone receptor-positive disease defined as IHC for ER or PR >/= 10% per local pathology review
• Men and women are eligible
• Age 70 and older at the time of protocol registration
• Non-metastatic, invasive breast cancer (scans are not required to document non-metastatic disease- any staging work-up is up to the treating provider's discretion)
• Recommended to have either neoadjuvant chemotherapy or adjuvant chemotherapy per their treating provider.
• Any surgery, nodal assessment, radiation, hormonal therapy is left up to the treating provider but should not occur concurrently with study therapy. If any additional chemotherapy is planned by a treating provider, this must occur AFTER all study-related chemotherapy is completed.
• Any patient receiving pre-operative hormonal therapy and who is then recommended for adjuvant chemotherapy is eligible, though hormonal therapy should be held during study treatment administration
• All study-related chemotherapy must be given prior to surgery if neoadjuvant therapy is planned or adjuvantly if postoperative chemotherapy is planned. For example, giving 6 doses pre-operatively and 6 doses postoperatively is not allowed on study.
• There are no restrictions on life expectancy, ECOG Performance Status, or baseline blood values or organ function; Appropriateness of chemotherapy treatment is left up to the treating provider but providers should be ok with the full starting doses of each agent.
• Participants must be willing to fill out surveys over time or designate a proxy to answer on their behalf.
• Ability to understand and the willingness to sign a written informed consent document.
• Patients who do not speak or read English are eligible as long as adequate interpreter services are available or the surveys are available in the preferred language (i.e. PRO surveys are available in many languages)

Exclusion Criteria:

• Participants who have already received chemotherapy for the current cancer. Prior diagnoses of breast cancers are allowed, provided that the treating provider feels that the current cancer represents a new primary breast cancer and not recurrent disease.
• Participants who are receiving any other investigational or anti-cancer agents. Any additional radiation, hormonal therapy or chemotherapy planned should be administered once the study treatments have completed.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to cyclophosphamide, carboplatin, and paclitaxel.
• Prior chemotherapy receipt is allowed in the setting of treatment of other/prior cancers, but no prior carboplatin (cohort 1), cyclophosphamide (cohort 2), or paclitaxel (both cohorts) receipt in the last 2 years is allowed (given toxicity and possible efficacy concerns

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Carboplatin + Paclitaxel; Paclitaxel will be administered intravenously 3 times per cycle; Carboplatin will be administered intravenously 3 times per cycle	Drug: Paclitaxel; The drug work by damaging the RNA or DNA that tells the cell how to copy itself in division. If the cells are unable to divide, they die.; Drug: Carboplatin; The drug work by damaging the RNA or DNA that tells the cell how to copy itself in division. If the cells are unable to divide, they die.
Experimental: Cyclophosphamide + Paclitaxel; Paclitaxel will be administered intravenously 3 times per cycle; Cyclophosphamide will be administered once per cycle	Drug: Paclitaxel; The drug work by damaging the RNA or DNA that tells the cell how to copy itself in division. If the cells are unable to divide, they die.; Drug: Cyclophosphamide; The drug work by damaging the RNA or DNA that tells the cell how to copy itself in division. If the cells are unable to divide, they die.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Toxicity and receipt of planned therapy (feasibility)	Examine the number of treatments received divided by the denominator of 12 treatments	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Using CTCAE standard reporting	2 years
NCI PRO-CTCAE	Examine patient reported CTCAEs on study treatment and their agreement with provider reports.	2 Years
Consequences of toxicity or disease events	Frequency of hospitalizations, deaths, emergency room visits	2 years
Invasive disease-free survival	recurrences and survival as per STEEP definitions and whether recurrences are local or distant	2 years
Overall survival	We will examine the time from study registration to death	2 years

Collaborators and Investigators

• Sponsor: Dana-Farber Cancer Institute
• Collaborators: Mayo Clinic
• Investigators: Principal Investigator: Rachel Freedman, MD, MPH, Dana-Farber Cancer Institute

Publications and helpful links

General Publications

• Freedman RA, Li T, Sedrak MS, Hopkins JO, Tayob N, Faggen MG, Sinclair NF, Chen WY, Parsons HA, Mayer EL, Lange PB, Basta AS, Perilla-Glen A, Lederman RI, Wong A, Tiwari A, McAllister SS, Mittendorf EA, Miller PG, Gibson CJ, Burstein HJ. 'ADVANCE' (a pilot trial) ADjuVANt chemotherapy in the elderly: Developing and evaluating lower-toxicity chemotherapy options for older patients with breast cancer. J Geriatr Oncol. 2023 Jan;14(1):101377. doi: 10.1016/j.jgo.2022.09.006. Epub 2022 Sep 23.

Study record dates

Study Major Dates

• Study Start (Actual): March 21, 2019
• Primary Completion (Actual): November 10, 2020
• Study Completion (Estimated): June 21, 2024

Study Registration Dates

• First Submitted: February 25, 2019
• First Submitted That Met QC Criteria: February 26, 2019
• First Posted (Actual): February 28, 2019

Study Record Updates

• Last Update Posted (Actual): January 10, 2024
• Last Update Submitted That Met QC Criteria: January 8, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Breast Cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Cyclophosphamide; Carboplatin; Paclitaxel
• Other Study ID Numbers: 19-031

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research
• IPD Sharing Time Frame: Data can be shared no earlier than 1 year following the date of publication
• IPD Sharing Access Criteria: BCH - Contact the Technology & Innovation Development Office at www.childrensinnovations.org or email TIDO@childrens.harvard.edu BIDMC - Contact the Beth Israel Deaconess Medical Center Technology Ventures Office at tvo@bidmc.harvard.edu BWH - Contact the Partners Innovations team at http://www.partners.org/innovation DFCI - Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu MGH - Contact the Partners Innovations team at http://www.partners.org/innovation
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No