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A Double-blind Study of Paclitaxel in Combination With Reparixin or Placebo for Metastatic Triple-Negative Breast Cancer (FRIDA)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2016 by Dompé Farmaceutici S.p.A
Sponsor:
Collaborator:
PRA Health Sciences
Information provided by (Responsible Party):
Dompé Farmaceutici S.p.A
ClinicalTrials.gov Identifier:
NCT02370238
First received: February 11, 2015
Last updated: October 20, 2016
Last verified: September 2016
  Purpose

Reparixin oral tablets are being tested as a CSC targeting agent in patients with metastatic non- human epidermal growth factor receptor (HER2)-amplified BC. An open label Phase 1b clinical study (REP0111) is ongoing (enrollment completed) in five US sites, under IND # 112502, to test safety, tolerability, pharmacokinetics and detect early signs of antitumor activity of increasing doses of reparixin oral tablets in combination with a fixed dose of weekly paclitaxel. The study has demonstrated safety and tolerability of the combination across the three dose levels explored and recorded objective responses in the published range for single agent weekly paclitaxel in the target population. The highest dose level explored (i.e., 1200 mg t.i.d.) was identified as the recommended phase 2 dose. Durable responses have been recorded in patients with TNBC.

The current phase 2 study thus aims to evaluate the Progression Free Survival of patients with metastatic TNBC [relapsed following (neo)adjuvant chemotherapy] receiving reparixin in combination with paclitaxel versus paclitaxel alone.


Condition Intervention Phase
Metastatic Breast Cancer
Drug: paclitaxel
Drug: Reparixin
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled Phase 2 Study of Paclitaxel in Combination With Reparixin Compared to Paclitaxel Alone as Front-line Therapy for Metastatic Triple- Negative Breast Cancer (FRIDA)

Resource links provided by NLM:


Further study details as provided by Dompé Farmaceutici S.p.A:

Primary Outcome Measures:
  • Progression Free Survival (PFS) [ Time Frame: 6 months ]
    Proportion of patients progression free at 6 months


Secondary Outcome Measures:
  • Median PFS (mPFS) [ Time Frame: 18 months ]
    Median PFS (mPFS) defined as the number of days between the date of randomization and the date of clinical disease progression (PD) according to RECIST criteria version 1.1

  • Overall Survival [ Time Frame: 18 months ]
    Overall Survival defined as the interval (days) between randomization and death from any cause.

  • Objective Response Rate [ Time Frame: 18 months ]
    Objective response rates (ORR) defined as the percentage of the patients reaching complete remission (CR), partial remission (PR) or stable disease (SD) according to RECIST criteria version 1.1.

  • AE [ Time Frame: during 14 days before start of treatment ]
    Adverse events

  • AE [ Time Frame: Days 1, 8 and 15 of each cycle ]
    Adverse events

  • AST [ Time Frame: Day 1 of each cycle ]
    aspartate aminotransferase

  • ALT [ Time Frame: Day 1 of each cycle ]
    alanine aminotransferase

  • ALP [ Time Frame: Day 1 of each cycle ]
    alkaline phosphatase

  • WBC [ Time Frame: Days 1, 8 and 15 of each cycle ]
    White cells differential counts


Other Outcome Measures:
  • TTM [ Time Frame: 18 months ]
    Median Time to new Metastasis (TTM)


Estimated Enrollment: 190
Study Start Date: June 2015
Estimated Study Completion Date: February 2018
Estimated Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: paclitaxel+reparixin

paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15) + reparixin oral tablets 1200 mg t.i.d.

continuing from D 1 to Day 21 of 28-day cycle

Drug: paclitaxel
paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15)
Drug: Reparixin
reparixin oral tablets 1200 mg t.i.d. continuing from D 1 to Day 21 of 28-day cycle
Active Comparator: paclitaxel+placebo
paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15) + placebo oral tablets 1200 mg t.i.d. continuing from D 1 to Day 21 of 28-day cycle
Drug: paclitaxel
paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15)
Drug: placebo
placebo oral tablets 1200 mg t.i.d. continuing from D 1 to Day 21 of 28-day cycle

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Female aged > 18 years.
  2. Patients with pathologically documented metastatic triple negative breast cancer (TNBC), eligible for treatment with paclitaxel. Paraffin-embedded tissue must be available from metastatic sites, if reasonably accessible, or from the primary tumor, to confirm the diagnosis of TNBC and for correlative studies (only on metastatic tissue). Fifteen slides can be obtained if the full block is not available to be sent or released.

    TNBC will be defined as breast cancer with <1% ER+ and <1% PgR+ cells, and HER2 immunohistochemistry score of 0 or 1+ and/or in situ hybridization (ISH) with HER2 gene copy number <4 or a ratio of less than 2 between HER2 gene copy number and centromere of chromosome 17. Patients whose metastatic disease is TNBC are eligible even when their primary tumor expressed hormone receptors and/or HER2.

  3. Patients must have relapsed following a prior (neo)adjuvant chemotherapy regimen. If a taxane (i.e., paclitaxel or docetaxel) was administered as part of the (neo)adjuvant regimen, PD must have occurred > 12 months from the end of previous (neo)adjuvant treatment. For non-taxane (neo)adjuvant regimen, PD must have occurred > 6 months from the end of previous (neo)adjuvant treatment
  4. Patients with at least one baseline measurable lesion according to RECIST criteria version 1.1.
  5. Zubrod (Eastern Co-operative Oncology Group [ECOG]) Performance Status (PS) of 0-1.
  6. Life expectancy of at least three months.
  7. Patients must be able to swallow and retain oral medication (intact tablet).
  8. Able to undergo all screening assessments outlined in the protocol.
  9. Adequate organ function (defined by the following parameters):

    1. Serum creatinine < 140 μmol/L (< 1.6 mg/dL) or creatinine clearance > 60 mL/min.
    2. Serum hemoglobin ≥ 9 g/dL; absolute neutrophil count ≥ 1.5 x 109/L; platelets ≥ 100 x 109/L.
    3. Serum bilirubin ≤ 1.5 x upper normal limit (UNL) except patients with Gilbert's syndrome
    4. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤ 2.5 x UNL but ≤ 5.0 x UNL in case of liver metastases; alkaline phosphatase (ALP) ≤ UNL but ≤ 2.5 x ULN in case of liver metastases; albumin within normal limits.
  10. No history or evidence by CT scan or MRI, of brain metastases or leptomeningeal disease.
  11. No known hepatitis B virus (not due to immunization), hepatitis C virus, human immunodeficiency virus-I and -II positive status.
  12. Dated and signed IEC/IRB-approved informed consent.

Exclusion Criteria:

  1. Newly diagnosed metastatic TNBC and TNBC not previously treated with (neo)adjuvant chemotherapy
  2. Prior therapy for metastatic TNBC (chemotherapy, hormone therapy or biological therapy), Patients may receive bisphosphonates and other therapies to treat bone metastases, however if used, bone lesions will not be considered as measurable disease.
  3. Less than four weeks since last radiotherapy (excluding palliative radiotherapy).
  4. Pregnancy or lactation or unwillingness to use adequate method of birth control.
  5. Neurological or psychiatric disorders which may influence understanding of study and informed consent procedures.
  6. Active or uncontrolled infection.
  7. Malabsorption syndrome, disease significantly affecting gastrointestinal function.
  8. G>1 pre-existing peripheral neuropathy
  9. Any other invasive malignancy from which the patient has been disease-free for less than 5 years with the exception of curatively treated basal or squamous cell skin cancer
  10. Hypersensitivity to:

    1. paclitaxel
    2. ibuprofen or to more than one non-steroidal anti-inflammatory drug.
    3. medications belonging to the class of sulfonamides, with the exception of sulfanilamides (e.g., sulfamethoxazole).
  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: NCT02370238

Contacts
Contact: Pieradelchi Ruffini, MD pieradelchi.ruffini@dompe.it

  Show 78 Study Locations
Sponsors and Collaborators
Dompé Farmaceutici S.p.A
PRA Health Sciences
  More Information

Additional Information:
Responsible Party: Dompé Farmaceutici S.p.A
ClinicalTrials.gov Identifier: NCT02370238     History of Changes
Other Study ID Numbers: REP0114
2014-004796-23 ( EudraCT Number )
Study First Received: February 11, 2015
Last Updated: October 20, 2016
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Dompé Farmaceutici S.p.A:
Triple negative metastatic breast cancer
Cancer Stem Cells

Additional relevant MeSH terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 26, 2017