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SPI-2012 vs Pegfilgrastim in the Management of Neutropenia in Participants With Breast Cancer With Docetaxel and Cyclophosphamide (ADVANCE) (ADVANCE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02643420
Recruitment Status : Completed
First Posted : December 31, 2015
Results First Posted : March 2, 2022
Last Update Posted : March 2, 2022
Sponsor:
Information provided by (Responsible Party):
Spectrum Pharmaceuticals, Inc

Study Description
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Brief Summary:
The purpose of this study was to compare the efficacy of a single dose of SPI-2012 versus pegfilgrastim in participants with early-stage breast cancer receiving docetaxel and cyclophosphamide (TC), as measured by the duration of severe neutropenia (DSN) in Cycle 1.

Condition or disease Intervention/treatment Phase
Neutropenia Breast Cancer Drug: SPI-2012 Drug: Pegfilgrastim Drug: Docetaxel Drug: Cyclophosphamide Phase 3

Detailed Description:

This was a Phase 3, randomized, open-label, active-controlled, multicenter study to compare the efficacy and safety of SPI-2012 vs pegfilgrastim in participants with breast cancer treated with TC chemotherapy.

Each cycle was 21 days. Four cycles were evaluated in this study. On Day 1 of each cycle, participants received TC chemotherapy. On Day 2 of each cycle, participants received study drug (SPI-2012 or pegfilgrastim).

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 406 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: RAnDomized Trial of SPI-2012 Versus Pegfilgrastim in the Management of Chemotherapy Induced Neutropenia in Breast CANCEr Patients Receiving Docetaxel and Cyclophosphamide (TC) (ADVANCE)
Actual Study Start Date : January 19, 2016
Actual Primary Completion Date : January 24, 2018
Actual Study Completion Date : October 31, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arms and Interventions
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Arm Intervention/treatment
Experimental: Arm 1: SPI-2012 and Docetaxel + Cyclophosphamide (TC)
Participants received SPI-2012 13.2 milligram (mg)/0.6 milliliter (mL) (3.6 mg Granulocyte Colony-Stimulating Factor [G-CSF]) fixed-dose subcutaneous (SC) injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy was administered on Day 1 of each cycle and included Docetaxel 75 mg/m^2 intravenous (IV) infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.
 Drug: SPI-2012
Single-use syringes for subcutaneous injection, administered on Day 2 of each cycle
Other Names:
  • Rolontis®
  • Eflapegrastim
  • (HM10460A)

Drug: Docetaxel
Standard therapy
Other Name: Taxotere

Drug: Cyclophosphamide
Standard therapy
Other Name: Cytoxan
Experimental: Arm 2: Pegfilgrastim and Docetaxel + Cyclophosphamide (TC)
Participants received pegfilgrastim 6 mg SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy on Day 1 of each cycle included Docetaxel 75 mg/m^2 IV infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.
 Drug: Pegfilgrastim
Single-dose subcutaneous injection administered on Day 2 of each cycle
Other Name: Neulasta®

Drug: Docetaxel
Standard therapy
Other Name: Taxotere

Drug: Cyclophosphamide
Standard therapy
Other Name: Cytoxan


Outcome Measures
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Primary Outcome Measures :
  1. Duration of Severe Neutropenia (DSN) in Cycle 1 [ Time Frame: Day 1 and Days 4-15 in Cycle 1 (each cycle was 21 days) ]
    DSN was defined as the number of days of severe neutropenia (absolute neutrophil count [ANC] <0.5×10^9/L), after the administration of study drug in Cycle 1.


Secondary Outcome Measures :
  1. Time to Absolute Neutrophil Count (ANC) Recovery in Cycle 1 [ Time Frame: Day 1 and Days 4, 15 in Cycle 1 (each cycle was 21 days) ]
    Time to ANC Recovery was defined as the time from chemotherapy administration until ANC increased to ≥1.5×10^9/L after the expected nadir within Cycle 1. Time to ANC recovery was assigned as 0 for participants whose ANC value never dropped below 1.5 x10^9/L.

  2. Depth of Absolute Neutrophil Count (ANC) Nadir in Cycle 1 [ Time Frame: Day 1 and Days 4, 15 in Cycle 1 (each cycle was 21 days) ]
    Depth of ANC Nadir was defined as the lowest ANC value after administration of study drug (SPI-2012 or Pegfilgrastim) in Cycle 1.

  3. Number of Participants With Febrile Neutropenia (FN) in Cycle 1 [ Time Frame: Day 1 and Days 4, 15 in Cycle 1 (each cycle was 21 days) ]
    FN was defined as an oral temperature > 38.3 degrees Celsius (C) (101.0 degrees Fahrenheit [F]) or two consecutive readings of >=38.0 degrees C (100.4 degrees F) for 2 hours and ANC <1.0×10^9/L.

  4. Duration of Severe Neutropenia in Cycle 2, 3 and 4 [ Time Frame: Days 1, 4, 7, 10, and 15 in cycles 2, 3, and 4 (each cycle was 21 days) ]
    DSN was defined as the number of days of severe neutropenia (ANC <0.5×10^9 /L) from the first occurrence of an ANC below the threshold in Cycles 2, 3, and 4.

  5. Number of Participants With Neutropenic Complications in Cycle 1 [ Time Frame: Day 1 and Days 4, 15 in Cycle 1 (each cycle was 21 days) ]
    Neutropenic complications refer to hospitalizations due to neutropenic events and/or the use of anti-infectives due to neutropenia.

  6. Number of Participants With Febrile Neutropenia in Cycles 2, 3, and 4 [ Time Frame: Days 1, 4, 7, 10, and 15 of Cycles 2, 3, and 4 (each cycle was 21 days) ]
    FN was defined as an oral temperature > 38.3 degrees C (101.0 degrees Fahrenheit [F]) or two consecutive readings of >=38.0 degrees C (100.4 degrees F) for 2 hours and ANC <1.0×10^9/L.

  7. Relative Dose Intensity (RDI) of TC (Docetaxel + Cyclophosphamide) in Cycles 1 to 4 [ Time Frame: Cycles 1 to 4 (each cycle was 21 days) ]
    RDI was defined as the percentage of the planned dose that each participant actually received during the study, expressed as the total dose received, divided by the total dose planned and multiplied by 100. The planned dose was defined as the dose that would be given if no doses were missed and/or no dose reductions were made for the number of cycles started. The total planned dose was the sum of planned doses over all cycles.

  8. Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: From the first dose of TC (Docetaxel + Cyclophosphamide) until 12 months after the last dose of study treatment (up to approximately 34 months) ]
    An adverse event (AE) is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product or study procedure, whether or not considered related to the medicinal product. A TEAE for Treatment Period is defined as adverse event with an onset date on or after the date of study drug administration through the end of treatment. TEAE for follow up is defined as any new onset or ongoing AE at the end of Treatment. SAE is defined as any AE which meets any of the following criteria: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in a persistent or significant disability/incapacity, results in a congenital anomaly/birth defect, includes important medical events.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • New diagnosis of histologically confirmed early-stage breast cancer (ESBC), defined as operable Stage I to Stage IIIA breast cancer
  • Candidate for adjuvant or neoadjuvant TC chemotherapy
  • Eastern Cooperative Oncology Group (ECOG) performance score ≤ 2
  • Absolute neutrophil count (ANC) ≥ 1.5×10^9/L
  • Platelet count ≥ 100×10^9/L
  • Hemoglobin > 9 g/dL
  • Creatinine clearance > 50 mL/min
  • Total bilirubin ≤ 1.5 mg/dL
  • Aspartate Aminotransferase per Serum Glutamic-Oxaloacetic Transaminase (AST/SGOT) and Alanine Aminotransferase per Serum Glutamic-Pyruvic Transaminase (ALT/SGPT) ≤ 2.5× Upper Limit of Normal (ULN).
  • Alkaline phosphatase ≤ 2.0×ULN

Key Exclusion Criteria:

  • Active concurrent malignancy (except non-melanoma skin cancer or carcinoma in situ of the cervix) or life-threatening disease
  • Locally recurrent or metastatic breast cancer
  • Known sensitivity to E. coli -derived products or to any products to be administered during dosing
  • Concurrent adjuvant cancer therapy
  • Previous exposure to filgrastim, pegfilgrastim, or other G-CSF products in clinical development within 12 months prior to the administration of study drug
  • Active infection, receiving anti-infectives, or any serious underlying medical condition that would impair ability to receive protocol treatment
  • Prior bone marrow or stem cell transplant
  • Use of any investigational drugs, biologics, or devices within 30 days prior to study treatment or plans to use any of these during the course of the study
  • Radiation therapy within 30 days prior to enrollment
  • Major surgery within 30 days prior to enrollment
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02643420


Locations
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Sponsors and Collaborators
Spectrum Pharmaceuticals, Inc
  Study Documents (Full-Text)

Documents provided by Spectrum Pharmaceuticals, Inc:
Study Protocol  [PDF] January 26, 2017
Statistical Analysis Plan  [PDF] July 31, 2018

More Information
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Responsible Party: Spectrum Pharmaceuticals, Inc
ClinicalTrials.gov Identifier: NCT02643420    
Other Study ID Numbers: SPI-GCF-301
First Posted: December 31, 2015    Key Record Dates
Results First Posted: March 2, 2022
Last Update Posted: March 2, 2022
Last Verified: February 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Spectrum Pharmaceuticals, Inc:
Neutropenia
Breast Cancer
Long-acting Myeloid Growth Factor
Early Stage Breast Cancer
Docetaxel + Cyclophosphamide (TC) chemotherapy
Additional relevant MeSH terms:
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Breast Neoplasms
Neutropenia
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Agranulocytosis
Leukopenia
Leukocyte Disorders
Hematologic Diseases
Cyclophosphamide
Docetaxel
 Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators