Paclitaxel and Carboplatin or Cyclophosphamide in Treating Older Patients with Non-metastatic Invasive Breast Cancer
This phase I trial studies how well paclitaxel and carboplatin or cyclophosphamide work in treating older patients with invasive breast cancer that has not spread to other places in the body. Drugs used in chemotherapy, such as paclitaxel, carboplatin, and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.
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 American Society of Clinical Oncology (ASCO) College of American Pathologist (CAP) guidelines.
- 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 estrogen receptor (ER) and progesterone receptor (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.
- 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, Eastern Cooperative Oncology Group (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 sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03858322.
PRIMARY OBJECTIVES:
I. Examine feasibility for each cohort, with feasibility defined as >= 80% of patients receiving >= 80% of intended therapy (including up to 2 dose changes for toxicity allowed).
SECONDARY/EXPLORATORY OBJECTIVES:
I. Examine changes in geriatric assessment/functional status over time for each cohort separately.
II. Describe the toxicities experienced by patients for each cohort using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (once every three weeks for 4 cycles).
III. Examine patient-reported outcomes using the NCI Patient Reported Outcome (PRO)-CTCAE system’s symptom reporting system at each treatment visit (once every three weeks for 4 cycles).
IV. Examine agreement between patient reported and provider reported CTCAEs.
V. Explore the differences in toxicities, severity of toxicities, and overall tolerance of each regimen.
VI. Describe any dose modifications, treatment omissions, hospitalizations, emergency room evaluations, and early treatment cessation (and the reasons for these events) while on study treatment in each cohort.
VII. Explore tumor genomics and tumor microenvironment on archived tissue samples obtained at baseline from surgery (adjuvant patients on each cohort).
VIII. Examine tumor genomics and tumor microenvironment on paired archived biopsy and surgical samples from those having pre-operative therapy (neoadjuvant patients on each cohort).
IX. Compare the toxicity predictions based on provider assessment at baseline, a toxicity prediction model at start of therapy and how these predictions correlate with actual grade 3 and higher toxicities experienced.
X. Examine blood for clonal hematopoiesis of indeterminate potential (CHIP) and associations of CHIP results with survival outcomes, breast cancer outcomes, and toxicity events, particularly hematologic toxicity events.
XI. Examine invasive disease free survival, pathological response rates (for those receiving chemotherapy in the pre-operative setting), overall survival, cause of death when available, breast cancer-specific survival, sites of recurrence using medical record information or phone contact with patients, their proxies, or their treatment team with regard to recurrence).
XII. Explore toxicity at one year after completion of therapy on study (and collect all other treatments patients received for their cancers).
XIII. Examine whether providers found the summary information provided from the baseline and end of treatment Geriatric Assessment helpful.
OUTLINE: Patients are assigned to 1 of 2 cohorts.
COHORT I: Patients with triple-negative breast cancer receive paclitaxel intravenously (IV) over 60 minutes and carboplatin IV over 30-60 minutes on days 1, 8, and 15. Cycles repeat every 21 days for 12 weeks in the absence of disease progression or unacceptable toxicity.
COHORT II: Patients with hormone-receptor positive breast cancer receive cyclophosphamide IV over 60 minutes on day 1 and paclitaxel IV over 60 minutes on days 1, 8, and 15. Cycles repeat every 21 days for 12 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 3 months, 12 months, and then every 6 months for up to 2 years.
Trial PhasePhase I
Trial Typetreatment
Lead OrganizationDana-Farber Harvard Cancer Center
Principal InvestigatorRachel A. Freedman
- Primary ID19-031
- Secondary IDsNCI-2019-02030
- ClinicalTrials.gov IDNCT03858322