Trial record 2 of 42 for:    MPDL3280A

Neoadjuvant Trial of Nab-Paclitaxel and MPDL3280A

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified August 2015 by M.D. Anderson Cancer Center
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT02530489
First received: August 19, 2015
Last updated: NA
Last verified: August 2015
History: No changes posted
  Purpose

The goal of this clinical research study is to learn if receiving MPDL3280A and abraxane (nab-paclitaxel) in combination before surgery and MPDL3280A alone after surgery can help to control breast cancer. The safety of this study drug combination will also be studied.


Condition Intervention Phase
Breast Cancer
Drug: MPDL3280A
Drug: Nab-paclitaxel
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Triple-Negative First-Line Study: Neoadjuvant Trial of Nab-Paclitaxel and MPDL3280A, a Pdl-1 Inhibitor in Patients With Triple Negative Breast Cancer

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Pathologic Complete Response (pCR) of MPDL3280A in Combination with Nab-paclitaxel [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    Pathologic complete response defined as no residual invasive disease in the breast or regional lymph nodes.


Secondary Outcome Measures:
  • Progression Free Survival (PFS) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    PFS estimated using the Kaplan-Meier method from the date of enrollment onto this study until the date of progression or death without evidence of progression.


Estimated Enrollment: 37
Study Start Date: December 2015
Estimated Primary Completion Date: December 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MPDL3280A + Nab-paclitaxel

MPDL3280A administered at 1200 mg by vein every 3 weeks for 12 weeks in the neoadjuvant setting in combination with Nab-paclitaxel 100 mg/m2 by vein weekly for 12 weeks.

Within 4 weeks after surgery, participants start another 4 cycles of MPDL3280A in the adjuvant setting to complete a total of 8 cycles of treatment with MPDL3280A.

Drug: MPDL3280A

1200 mg by vein every 3 weeks for 12 weeks before surgery.

Within 4 weeks after surgery, participants start another 4 cycles of MPDL3280A.

Drug: Nab-paclitaxel
100 mg/m2 by vein weekly for 12 weeks before surgery.
Other Names:
  • Paclitaxel
  • Abraxane
  • ABI-007

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Signed written informed consent
  2. Histologically confirmed primary invasive adenocarcinoma of the breast with the size of the primary tumor being at least 1.5 cm on imaging by either mammography, ultrasound or breast MRI
  3. ER and PR expression both <10% by immunohistochemistry (IHC) and HER2 0 or 1+ by IHC or non-amplified HER2 expression as determined by Fluorescence In Situ Hybridization (FISH)
  4. No prior treatment for primary invasive adenocarcinoma of the breast such as irradiation, chemotherapy, hormonal therapy, immunotherapy, investigational therapy or surgery other than the anthracycline and cyclophosphamide chemotherapy with or without 5-fluorouracil given as part of participation in protocol 2014-0185. Treatment for ductal carcinoma in situ is allowed, such as surgery, hormonal therapy and radiotherapy
  5. ECOG performance status of 0-1
  6. Baseline MUGA or echocardiogram scans with LVEF of > 50%
  7. Patient must have adequate organ function as determined by the following laboratory values: ANC >/= 1500 cells/uL, WBC counts > 2500/uL, Lymphocyte count >/= 300/uL, Platelet count >/=100,000/uL; Hemoglobin >/= 9.0 g/dL, Total bilirubin </= 1.5 x upper limit of normal (ULN) with the following exception: Patients with known Gilbert disease who have serum bilirubin level </= 3 x ULN may be enrolled. AST and ALT </= 3.0 x ULN with the following exception: Patients with liver involvement: AST and/or ALT </= 5 x ULN, Alkaline phosphatase </= 2.5 x ULN with the following exception: Patients with documented liver involvement or bone metastases: alkaline phosphatase </= 5 x ULN
  8. Serum creatinine </= 1.5 x ULN or creatinine clearance >/= 50 mL/min on the basis of the Cockcroft-Gault glomerular filtration rate estimation: (140 - age) x (weight in kg) x (0.85 if female)/ 72 x (serum creatinine in mg/dL), INR and aPTT </= 1.5 x ULN. This applies only to patients who do not receive therapeutic anticoagulation; patients receiving therapeutic anticoagulation (such as low-molecular-weight heparin or warfarin) should be on a stable dose
  9. Men or women 18 years of age or older
  10. Women of childbearing potential must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 8 weeks after the last dose of investigational product in such a manner that the risk of pregnancy is minimized. Men on study also must be using contraception. Women of childbearing potential (WOCBP) are women who have not been postmenopausal greater than 1 year or undergone a hysterectomy or bilateral oophorectomy
  11. Negative serum or urine pregnancy test for women within 72 hours of receiving the first dose of the study medication for women of childbearing potential
  12. Participated on protocol 2014-0185 TNBC Neoadjuvant Triaging protocol and classified as a "chemotherapy-insensitive" after anthracycline-based chemotherapy either by insufficient tumor shrinkage (<80%) by diagnostic imaging or classified as a non-responder by the molecular predictor as part of their participation in protocol 2014-0185

Exclusion Criteria:

  1. Women who are pregnant or breast-feeding
  2. Known metastatic disease
  3. Disease free of prior malignancy for < 5 years with the exception of curatively treated basal cell carcinoma of the skin, carcinoma in situ of the cervix, or transitional cell carcinoma.
  4. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
  5. Has had major surgery within 21 days before Cycle 1, Day 1
  6. Uncontrolled inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
  7. Myocardial infarction within 6 months before starting therapy, symptomatic congestive heart failure (New York Heart Association > class II), unstable angina, or unstable cardiac arrhythmia requiring medication
  8. Serious intercurrent infections or non-malignant medical illness that are uncontrolled or the control of which may be jeopardized by this therapy
  9. Psychiatric disorders or other conditions rendering the subject incapable of complying with the requirements of the protocols
  10. History or risk of autoimmune disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis. Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be eligible. Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen may be eligible.
  11. Continued from #9: Patients with eczema, psoriasis, lichen simplex chronicum of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions: Patients with psoriasis must have a baseline ophthalmologic exam to rule out ocular manifestations Rash must cover less than 10% of body surface area (BSA) Disease is well controlled at baseline and only requiring low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, fluocinolone 0.01%, desonide 0.05%, alclometasone dipropionate 0.05%) No acute exacerbations of underlying condition within the last 12 months (not requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids)
  12. Known to be human immunodeficiency virus positive
  13. Patients with prior allogeneic stem cell or solid organ transplantation
  14. History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterates, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted
  15. Patients with active hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C. Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen [anti HBc] antibody test) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA
  16. Active tuberculosis
  17. Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1 or anticipation that such a live, attenuated vaccine will be required during the study. Influenza vaccination should be given during influenza season only (approximately October to March). Patients must not receive live, attenuated influenza vaccine (e.g., FluMist) within 4 weeks prior to Cycle 1, Day 1 or at any time during the study
  18. Treatment with systemic immunostimulatory agents (including but not limited to interferons or IL-2) within 4 weeks or five half-lives of the drug, whichever is shorter
  19. Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [TNF] agents), or anticipated requirement for systemic immunosuppressive medications during the trial. Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., dexamethasone prior to the anthracycline-based chemotherapy for nausea) may be enrolled in the study. The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) is allowed
  20. Concurrent disease or condition that would interfere with study participation or safety, such as any of the following: Active, clinically significant infection either grade > 2 by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 or requiring the use of parenteral anti-microbial agents within 14 days before Day 1 of study drug, Clinically significant bleeding diathesis or coagulopathy, including known platelet function disorders, Non-healing wound, ulcer, or bone fracture
  21. Known hypersensitivity to any of the components of MPDL3280A or nab-paclitaxel
  22. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02530489

Contacts
Contact: Jennifer Litton, MD 713-792-2817

Locations
United States, Texas
University of Texas MD Anderson Cancer Center Not yet recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Genentech, Inc.
Investigators
Principal Investigator: Jennifer Litton, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02530489     History of Changes
Other Study ID Numbers: 2014-1043
Study First Received: August 19, 2015
Last Updated: August 19, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Breast Cancer
Triple negative breast cancer
TNBC
Invasive adenocarcinoma of the breast
MPDL3280A
Nab-paclitaxel
Paclitaxel
Abraxane
ABI-007

Additional relevant MeSH terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Paclitaxel
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on August 30, 2015