Phase 2 Study of Standard Chemotherapy With Trastuzumab, Plus or Minus Pertuzumab, for Pre-treated Metastatic Breast Cancer

NCT02229149 | Terminated Phase 2 DMC

• 2 other identifiers: 13011ML29212
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized phase 2 study will seek to determine the effectiveness of chemotherapy (physician's choice of vinorelbine, taxane \[paclitaxel, docetaxel or nab paclitaxel\] or capecitabine) plus trastuzumab vs chemotherapy (physician's choice) plus trastuzumab plus pertuzumab in women with HER2-overexpressing metastatic breast (MBC) that has been previously treated with ado-trastuzumab emtansine (T-DM1) in the metastatic setting.

Conditions

Breast Neoplasms; Malignant Tumor of the Breast

Keywords

breast cancer; metastatic breast cancer; HER2+ breast cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  The primary objective of this study is to compare progression-free survival (PFS \[also known as time to disease progression\]) with the addition of pertuzumab to trastuzumab plus physician's choice of chemotherapy versus trastuzumab plus physician's choice of chemotherapy in patients who have previously received treatment with ado-trastuzumab emtansine (TDM1) for HER2+ metastatic breast cancer.

  2 years

Secondary Outcomes (5)

• Progression-free survival (PFS) in patients (pts) with prior pertuzumab

  2 years

• Progression-free survival (PFS) in pts with prior chemotherapy

  2 years

• Number of patients with complete and partial responses

  2 years

• Overall survival

  2 years

• Number of adverse events and serious adverse events

  2 years

Study Arms (2)

Triple Therapy

EXPERIMENTAL

Physician's choice of chemotherapy plus trastuzumab plus pertuzumab * trastuzumab, given as a loading dose of 8 mg/kg intravenously (IV, or through the vein) on Day 1 followed by 6 mg/kg IV every 3 weeks thereafter, AND * physician's choice of chemotherapy: 1. Vinorelbine 25 mg/m2 IV weekly times 3 with 1 week off; OR 2. Paclitaxel 80 mg/m2 IV weekly times 3 with 1 week off; OR 3. Nab-Paclitaxel 100 mg/m2 IV weekly times 3 with 1 week off; OR 4. Docetaxel 75 mg/m2 IV every 3 weeks; OR 5. Capecitabine 1500 mg by mouth twice a day (PO BID) 14 days on and then 7 days off. * AND pertuzumab given as a loading dose of 840 mg IV on Day 1 followed by 420 mg IV every 3 weeks.

Drug: Trastuzumab; Drug: Pertuzumab; Drug: Vinorelbine, Paclitaxel, Nab-Paclitaxel , Docetaxel, Capecitabine

Double Therapy

ACTIVE COMPARATOR

Physician's choice of chemotherapy plus trastuzumab * trastuzumab, given as a loading dose of 8 mg/kg intravenously (IV, or through the vein) on Day 1 followed by 6 mg/kg IV every 3 weeks thereafter, AND * physician's choice of chemotherapy: 1. Vinorelbine 25 mg/m2 IV weekly times 3 with 1 week off; OR 2. Paclitaxel 80 mg/m2 IV weekly times 3 with 1 week off; OR 3. Nab-Paclitaxel 100 mg/m2 IV weekly times 3 with 1 week off; OR 4. Docetaxel 75 mg/m2 IV every 3 weeks; OR 5. Capecitabine 1500 mg PO BID 14 days on and then 7 days off.

Drug: Trastuzumab; Drug: Vinorelbine, Paclitaxel, Nab-Paclitaxel , Docetaxel, Capecitabine

Interventions

Trastuzumab DRUG

Treatment for all patients will consist of trastuzumab, given as a loading dose of 8 mg/kg IV on Day 1 followed by 6 mg/kg IV every 3 weeks thereafter. Patients randomized to the chemotherapy plus trastuzumab arm (without pertuzumab) can receive trastuzumab 6 mg/kg IV every 3 weeks if they are receiving docetaxel or capecitabine on a 3-week cycle, or 4 mg/kg IV every 2 weeks if they are receiving vinorelbine, paclitaxel, or nab-paclitaxel on a 4-week cycle. The loading dose for all patients remains 8 mg/kg. For patients randomized to the chemotherapy plus trastuzumab plus pertuzumab arm, both trastuzumab and pertuzumab need to be administered every 3 weeks regardless of which chemotherapy agent they are receiving.

Also known as: Herclon, Herceptin

Double Therapy; Triple Therapy

Pertuzumab DRUG

pertuzumab given as a loading dose of 840 mg IV on Day 1 followed by 420 mg IV every 3 weeks.

Also known as: 2C4, Perjeta, Omnitarg

Triple Therapy

Vinorelbine, Paclitaxel, Nab-Paclitaxel , Docetaxel, Capecitabine DRUG

physician's choice of chemotherapy: * Vinorelbine 25 mg/m2 IV weekly times 3 with 1 week off; OR * Paclitaxel 80 mg/m2 IV weekly times 3 with 1 week off; OR * Nab-Paclitaxel 100 mg/m2 IV weekly times 3 with 1 week off; OR * Docetaxel 75 mg/m2 IV every 3 weeks; OR * Capecitabine 1500 mg by mouth twice a day (PO BID) 14 days on and then 7 days off.

Also known as: Navelbine, Abraxane, Taxol, Taxotere, Docecad, Xeloda

Double Therapy; Triple Therapy

Eligibility Criteria

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

You may qualify if:

• Female, Age ≥ 18 years
• Histologic or cytologic confirmation of human epidermal growth factor receptor 2 (HER2)-positive breast cancer according to most recent biopsy (local testing permitted)
• Measurable or evaluable metastatic disease by Response Evaluation Criteria in Solid Tumors (RECIST) (v1.1)
• Previous treatment with ado-trastuzumab emtansine (T-DM1) for metastatic disease
• a. Prior therapy with pertuzumab is allowed but not required
• At least 1 but no more than 3 prior chemotherapy regimens for metastatic breast cancer (MBC)
• Life expectancy \> 6 months
• Eastern Cooperative Group (ECOG) performance status ≤ 2
• Left Ventricular Ejection Fraction (LVEF) ≥ 50% at baseline as determined by either echocardiogram (ECHO) or Multi Gated Acquisition Scan (MUGA) and within normal limits per institutional guidelines
• Adequate bone marrow function as indicated by the following:
• Absolute Neutrophil Count (ANC) ≥1500/uL (or 1500 per microliter)
• Platelets ≥100,000/uL
• Hemoglobin \>9 g/dL
• Adequate renal function, as indicated by creatinine \<1.5 times upper limit of normal (ULN)
• Adequate liver function, as indicated by bilirubin \<1.5 times ULN

You may not qualify if:

• Patients will be excluded from the study based on the following criteria:
• Prior treatment in the metastatic setting with the agent chosen as physician's choice of chemotherapy
• Active infection
• Uncontrolled central nervous system metastases, defined as clinical or radiologic evidence of progression of brain metastases or clinical signs of leptomeningeal disease
• a. Patients with treated brain metastases are eligible provided they do not have clinical or radiologic evidence of disease progression and have been off of dexamethasone for at least 3 weeks
• Patient is pregnant or lactating
• Prior chemotherapy within the last 3 weeks (last 6 weeks for nitrosureas/mitomycin)
• Prior radiation therapy within the last 2 weeks; prior radiation therapy to indicator lesion (unless objective disease recurrence or progression within the radiation portal has been documented since completion of radiation).
• Requirement for chronic steroid therapy with a requirement for \> 5mg/day of prednisone or the equivalent.
• a. Treatment with physiologic doses of hydrocortisone up to 20 mg daily (QD) is allowed.
• Requirement for immunosuppressive therapy, such as those used to treat autoimmune disease.
• Concomitant malignancies or previous malignancies within the last 3 years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
• History of significant cardiac disease, cardiac risk factors or uncontrolled arrhythmias
• Ejection fraction \<50% or below the lower limit of the institutional normal range, whichever is lower
• Known hypersensitivity to trastuzumab or pertuzumab

Sponsors & Collaborators

• US Oncology Research: lead
• Genentech, Inc.: collaborator

Study Sites (1)

19 Sites

Multiple Locations, Texas, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Trastuzumab; pertuzumab; Vinorelbine; Paclitaxel; 130-nm albumin-bound paclitaxel; Docetaxel; Capecitabine; Albumin-Bound Paclitaxel

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Albumins

Study Officials

• Neelima Denduluri, MD

  US Oncology Research, McKesson Specialty Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 27, 2014
• First Posted: August 29, 2014
• Study Start: December 1, 2014
• Primary Completion: January 1, 2022
• Study Completion: January 1, 2022
• Last Updated: December 2, 2022

Record last verified: 2022-11

Locations

US (1)