Nab-Paclitaxel in Treating Older Patients With Locally Advanced or Metastatic Breast Cancer

PRIMARY OBJECTIVE:

I. To evaluate the tolerability (grade 2-5 toxicity, neuropathy grade 2 or higher, need for dose reductions, or delays) of weekly nab-paclitaxel in older adults with locally advanced or metastatic breast cancer.

SECONDARY OBJECTIVES:

I. To evaluate the efficacy (response and time to progression) of weekly nab-paclitaxel in older adults with locally advanced or metastatic breast cancer using a stratification factor based on patient age (at least 5 patients age 75 years or older and no more than 15 patients age 65-70 years).

II. To explore predictors of the need for dose reduction, dose delays, or grade 2-5 toxicity and neuropathy grade 2 or higher based on a cancer-specific geriatric assessment.

OUTLINE:

Patients receive nab-paclitaxel intravenously (IV) over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

• Laboratory Biomarker Analysis (Other): Correlative studies
• Nab-paclitaxel (Drug), also known as ABI 007, ABI-007, Abraxane, Albumin-bound Paclitaxel, Albumin-Stabilized Nanoparticle Paclitaxel, Nanoparticle Albumin-bound Paclitaxel, Nanoparticle Paclitaxel, Paclitaxel Albumin, paclitaxel albumin-stabilized nanoparticle formulation, protein-bound paclitaxel: Given IV
• Questionnaire Administration (Other): Ancillary studies

Primary outcomes

• Percent of Participants With Grade 2-5 Toxicity Using National Cancer Institute Common Toxicity Criteria Version 4.0 [During and after treatment, up to 2.5 years]: Will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Rates and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated for grade 2 or higher toxicities attributed to treatment.
• Percent of Participants With Grade 3 or Higher Toxicities Attributable to Treatment [On treatment, 28 days per cycle up to 30 months]: Will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Rates and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated for grade 3 or higher toxicities attributed to treatment.
• Rate of Participants With a Dose Reduction [On treatment, up to 30 months]: Rates and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated for dose reduction.
• Rate of Participants Requiring Dose Holds [While on treatment, up to 30 months]: Rates and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated for dose reduction.

Secondary outcomes

• Response Determined by Response Evaluation Criteria in Solid Tumors [Up to 2.5 years]: Rates and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated for objective response rate (complete response \[CR\] + partial response \[PR\]). RECIST: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10 mm Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. Additionally, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study
• Median Progression Free Survival (PFS) [From the date treatment begins until the first date on which recurrence, progression, or death due to any cause, assessed for about 1.5 years]: PFS will be estimated using the product limit method of Kaplan and Meier.
• Cancer-specific Geriatric (CARG) Assessment [CARG measured prior to treatment, toxicities and dose reduction measured up to 30 months]: General linear models and descriptive methods will be used to explore factors as identified by a CARG assessment that may be predictive of toxicity (grade 3 or higher adverse events) or dose reduction. The cancer specific geriatric assessment score includes an evaluation of functional status, co-morbidity, cognition, psychological stats, social functioning and support, and nutritional status. It assesses a patient's age, gender, height, weight, cancer type, dosage, number of chemotherapy agents, hemoglobin, hearing, number of falls in past 6 months, able to take own medicine, whether walking is limited, have physical or emotional problems interfered with social activities and serum creatinine. Scores can range from 0 to to 1, with a higher score indicating higher risk of chemotherapy toxicity. Scores from 0 to 5 are considered low risk, 6 to 9 are considered intermediate risk, and 10 to 19 are considered high risk.

Sex: All, ages: 65 Years to any

Inclusion Criteria:

* Locally advanced or metastatic breast cancer
* Any estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2 (Her2neu) status as long as the patient will receive nab-paclitaxel alone
* First or second line chemotherapy treatment for metastatic disease
* Karnofsky performance status (KPS) >= 70%
* Resolution of grade >= 2 toxicity from prior therapy (other than alopecia)
* Peripheral neuropathy =< grade 1
* Absolute neutrophil count >= 1,500/mm\^3
* Platelets >= 100,000 cells/mm\^3
* Hemoglobin (Hb) >= 9.0 g/dl
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x institutional upper limit of normal
* Alkaline phosphatase =< 2.5 x upper limit of normal unless bone metastasis are present in the absence of liver metastases
* Bilirubin =< 1.5 mg/dl
* Creatinine clearance (calculated or 24 hour) >= 30 ml/min
* Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

* Patients may not be receiving any other investigational agents
* Untreated central nervous system (CNS) metastases or symptomatic CNS metastases requiring escalating doses of corticosteroids
* Known history of allergic reactions to paclitaxel
* Presence of any serious or uncontrolled infection
* Receipt of a taxane for adjuvant therapy or metastatic disease in the last 12 months

Participant flow

Outcome results

• Percent of Participants With Grade 2-5 Toxicity Using National Cancer Institute Common Toxicity Criteria Version 4.0 (Primary), Number, percentage of participants: Treatment (Nab-paclitaxel) 90 (76 to 97)
• Percent of Participants With Grade 3 or Higher Toxicities Attributable to Treatment (Primary), Number, percentage of participants: Treatment (Nab-paclitaxel) 58 (41 to 73)
• Rate of Participants With a Dose Reduction (Primary), Number, percentage of participants: Treatment (Nab-paclitaxel) 50 (34 to 66)
• Rate of Participants Requiring Dose Holds (Primary), Number, percentage of participants: Treatment (Nab-paclitaxel) 75 (59 to 87)
• Response Determined by Response Evaluation Criteria in Solid Tumors (Secondary), Count of participants, Participants: Treatment (Nab-paclitaxel) 1
• Median Progression Free Survival (PFS) (Secondary), Median, months: Treatment (Nab-paclitaxel) 6.5 (5.5 to NA)
• Cancer-specific Geriatric (CARG) Assessment (Secondary), Count of participants, Participants: Treatment (Nab-paclitaxel) 21 (p 0.01)

Adverse events

Time frame: On study, up to 2.5 years

Serious adverse events by term

Other adverse events by term

• Hurria A, Soto-Perez-de-Celis E, Blanchard S, Burhenn P, Yeon CH, Yuan Y, Li D, Katheria V, Waisman JR, Luu TH, Somlo G, Noonan AM, Lee T, Sudan N, Chung S, Rotter A, Arsenyan A, Levi A, Choi J, Rubalcava A, Morrison R, Mortimer JE. A Phase II Trial of Older Adults With Metastatic Breast Cancer Receiving nab-Paclitaxel: Melding the Fields of Geriatrics and Oncology. Clin Breast Cancer. 2019 Apr;19(2):89-96. doi: 10.1016/j.clbc.2018.10.002. Epub 2018 Oct 16. PMID 30503309

• Study Protocol and Statistical Analysis Plan (PDF, 2019-09-23)

• Mina Sedrak, Principal investigator, City of Hope Medical Center

NIH grants: P30CA033572