Assessing the Response Rate of Neo-adjuvant Paclitaxel (Taxol) in Nigerian Women With Breast Cancer

NCT03058939 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: IRB15-1005
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is a two-stage phase II study with a single arm design. It will be conducted in women with breast cancer with stages IIA to IIIC (defined by AJCC 2009 classification) of all histological subtypes. All patients will receive 16 doses of paclitaxel; three breast ultrasound tests and tumor pathologic response evaluation will be used to assess the response to treatment.

Conditions

Breast Cancer; Breast Cancer Stage II; Breast Cancer Stage III

Keywords

Breast Cancer; Breast Cancer Stage II; Breast Cancer Stage III; Paclitaxel; Taxol

Outcome Measures

Primary Outcomes (2)

• Measure overall clinical response rate (OCR)

  OCR will be calculated as the proportion of patients with an overall response of complete clinical response (CCR) or partial clinical response (PCR), where tumor response is based on change in tumor diameter after treatment.

  24 months

• Measure of complete pathologic response (pCR)

  The absence of residual invasive disease in the breast and in the axillary lymph nodes at the completion of treatment will be measured.

  24 months

Secondary Outcomes (8)

• Number of participants with adverse events

  24 months

• Time until progression free survival (PFS)

  From start date of therapy to the date of first documented disease progression or death from any cause, whichever may come first, assessed up to 100 months

• Duration of response (DOR)

  From first reponse to the date of first documented disease progression, assessed up to 24 months

• Analysis of changes from baseline using the quality of life (QoL) instrument

  From start date of therapy to the date of first documented disease progression or death from any cause, whichever may come first, assessed up to 100 months.

• To assess the genetic and epigenetic factors associated with breast cancer in Nigeria

  From start date of therapy to the date of death from any cause, assessed up to 100 months

Study Arms (6)

Paclitaxel

EXPERIMENTAL

Investigators plan to treat patients with paclitaxel weekly for a total of approximately 16 weeks (8 weeks before ultrasonography for response assessment and 8 weeks before surgery in good responders). Paclitaxel 80mg/m2 will be given on days 1, 8, 15 and so on for a total of 8 doses.

Drug: Paclitaxel

Carboplatin

OTHER

After first 8 weeks of paclitaxel, those with progressive disease (based on breast US assessment) or partial response but inoperable will have carboplatin added to their regimen. Patients will receive 8 cycles of weekly paclitaxel and carboplatin (PC).

Drug: Carboplatin

Fluorouracil Epirubicin Hydrochloride Cyclophonsphamide (FEC)

OTHER

Patients with poor response to 8 courses of paclitaxel followed by 8 courses of PC based on ultrasound assessment will be regarded as failing to respond to treatment. These patients will receive 4 cycles of 3-weekly FEC and will be followed up.

Drug: FEC

LHRH (luteinizing hormone-releasing hormone)

OTHER

All Premenopausal patients will receive LHRH agonist for two years for contraception and fertility preservation.

Drug: LHRH agonist

Tamoxifen or letrozole

OTHER

Hormone-receptor positive patients will receive hormonal therapy with tamoxifen or letrozole after surgery, radiotherapy and LHRH agonist according to the expression of hormone receptors and according to the state of primary menopause at the onset of the study.

Drug: Tamoxifen; Drug: Letrozole

Herceptin SC and Perjeta

OTHER

Patients with HER2-positive disease (see glossary and section 10.3) will receive 5 three-weekly courses of trastuzumab (Herceptin SC) with pertuzumab (Perjeta). After that pts will continue receiving trastuzumab to complete total of 18 doses within 1 year of treatment.

Drug: Perjeta; Drug: Herceptin SC

Interventions

Paclitaxel DRUG

Administered to all patients for a minimum of 8 doses with a possible maximum of 16 doses.

Also known as: Taxol

Paclitaxel

Perjeta DRUG

Only administered to patients with HER2-positive disease.

Also known as: Pertuzumab

Herceptin SC and Perjeta

Herceptin SC DRUG

Only administered to patients with HER2-positive disease.

Also known as: Trastuzumab

Herceptin SC and Perjeta

Tamoxifen DRUG

Only administered to hormone-receptor positive patients. Patients will receive tamoxifen or letrozole.

Tamoxifen or letrozole

Letrozole DRUG

Only administered to hormone-receptor positive patients. Patients will receive tamoxifen or letrozole.

Tamoxifen or letrozole

LHRH agonist DRUG

Administered to all premenopausal patients.

LHRH (luteinizing hormone-releasing hormone)

FEC DRUG

Only administered to patients who received paclitaxel and carboplatin, and were assessed as having poor response (defined as stable disease or progressive disease or partial response inoperable).

Fluorouracil Epirubicin Hydrochloride Cyclophonsphamide (FEC)

Carboplatin DRUG

Only administered to patients who receive paclitaxel and were assessed as having poor response (defined as stable disease or progressive disease or partial response inoperable).

Carboplatin

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women ages of 18 to 70 years old.
• Biopsy-accessible breast tumor of significant size for core needle biopsy (≥ 2cm).
• Patients with histologically confirmed carcinoma of the female breast with any or unknown HRs/HER2 status
• Clinical stages IIA -IIIC. (AJCC 2009) (Appendix A)
• Chemotherapy-naïve patients (for this malignancy)
• Performance status: ECOG performance status 0-3 (Appendix B)
• Non-pregnant and not nursing. Women of childbearing potential must take the pregnancy test and must commit to receive LHRH agonist Zoladex (goserelin) for two years starting from the commencement of the study medications.
• Required Initial Laboratory Data. Adequate hematologic, renal and hepatic function, as defined by each of the following:
• Granulocyte ≥ 1,500/μL
• Platelet count ≥ 100,000/μL
• Absolute neutrophil count (ANC) ≥ l500/μL
• Hemoglobin³10g/dL
• Bilirubin ≤ 1.5 x upper limit of normal
• SGOT and SGPT \< 2.5 x upper limit of normal for patients without liver metastases
• Creatinine within institutional normal limits or glomerular filtration rate ≥ 30 mL/min/1.73 m2 by CKD EPI equation (see http://mdrd.com/ for calculator)

You may not qualify if:

• Pregnant or lactating women. Women of childbearing potential not using a reliable and appropriate contraceptive method. Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential.
• Patients will agree to continue the use of acceptable form of contraception for 30 days from the date of last drug administration.
• Patients with brain metastasis.
• Serious, uncontrolled, concurrent infection(s).
• Patients who have received more than 4 weeks of tamoxifen therapy for this malignancy. Patient who have received tamoxifen or raloxifene for purposes of chemoprevention (e.g. Breast Cancer Prevention Trial or for other past indications (including previous breast cancer) are eligible. Tamoxifen or raloxifene therapy will be discontinued at least one month before the patient is enrolled on this study.
• Treatment for other carcinomas within the last 5 years, except non-melanoma skin cancer and treated cervical carcinoma in-situ (CCIS).
• Participation in any investigational drug study within 4 weeks preceding the start of study treatment.
• Other serious uncontrolled medical conditions that the investigator feels might compromise study participation including but not limited to chronic or active infection, HIV-positive patient, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled Diabetes mellitus, or psychiatric illness/social situations that would limit compliance with study requirements.
• Unwillingness to participate or inability to comply with the protocol for the duration of the study.

Sponsors & Collaborators

• University of Chicago: lead

Study Sites (1)

Lagos State University College of Medicine

Ikeja, Lagos, Nigeria

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Paclitaxel; pertuzumab; Trastuzumab; Tamoxifen; Letrozole; Gonadotropin-Releasing Hormone; Carboplatin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Nitriles; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Oligopeptides; Nerve Tissue Proteins; Coordination Complexes

Study Officials

• Olufunmilayo I. Olopade, MD

  University of Chicago Center for Global Health

  PRINCIPAL INVESTIGATOR

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: February 2, 2017
• First Posted: February 23, 2017
• Study Start: November 1, 2018
• Primary Completion: April 1, 2019
• Study Completion: June 1, 2019
• Last Updated: April 22, 2019

Record last verified: 2019-04

Locations

NG (1)