Breast Cancer Study: Paclitaxel Versus Paclitaxel Plus Sorafenib in Second- or Third-line Treatment

NCT01320111 | Completed Phase 2 DMC

• 2 other identifiers: GMIHO-008/20082009-018025-73
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

Brief Summary

AIM OF STUDY Primary Efficacy Variable: The primary study objective is the proof of efficacy, measured by progression free survival (PFS) in the treatment of metastatic or locally inoperable recurrent breast cancer. Progression-free survival (PFS) is defined as the time from randomisation to disease progression or death. Secondary Efficacy Variables:

• Clinical benefit (CR+PR+SD)
• ORR (CR+PR)
• Time to progression
• Time to next Treatment (TTT)
• Overall survival
• Safety profile

Conditions

Metastatic Breast Cancer

Keywords

progression free survival; paclitaxel; sorafenib; metastatic breast cancer

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS)

  The primary study objective is the proof of efficacy, measured by progression free survival (PFS) in the treatment of metastatic or locally inoperable recurrent breast cancer. Progression-free survival (PFS) is defined as the time from randomisation to disease progression or death.

  app. 3 yrs

Secondary Outcomes (1)

• Secondary Efficacy Variables

  app. 3 years

Study Arms (2)

Arm 1: PA

ACTIVE COMPARATOR

patient is treated with paclitaxel only

Drug: Paclitaxel

Arm 2: PASO

EXPERIMENTAL

patient is treated with paclitaxel AND sorafenib

Drug: Paclitaxel and Sorafenib

Interventions

Paclitaxel and Sorafenib DRUG

intravenous solution, 80 mg/sqm, 3 times per cycle, with one cycle = 28 d and application at days 1, 8 and 15 AND pills (200mg), cycle 1: 400 mg / day cycle 2: 600 mg / day from cycle 3: 800 mg / day

Also known as: sorafenib = nexavar

Arm 2: PASO

Paclitaxel DRUG

intravenous solution, 80 mg/sqm, 3 times per cycle, with one cycle = 28 d and application at days 1, 8 and 15

Arm 1: PA

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed adenocarcinoma of the breast
• HER-2/neu negative (primary tumour site HER-2/neu negative by ICH/FISH test)
• Second till third-line of chemotherapy
• Female, age ≥ 18 years.
• ECOG Performance Status of 0 or 1 (Karnofsky-Index ≥ 70%)
• Life expectancy of at least 12 weeks.
• Subjects with at least one uni-dimensional (for RECIST 1.1) measurable lesion. Lesions must be measured by Xray (pulmonary lesions only) or CT-scan or MRI (Patients with only measurable bone lesions can be also included, as long they meet the criteria for RECIST 1.1.; means, lytic bone lesions or mixed lytic-blastic bone lesions with identifiable soft tissue components.)
• No prior therapy for locally recurrent or metastatic disease with TKI's (RAS/Raf, MEK, AKT), mTOR inhibitors and angiogenesis inhibitors (VEGV/VEGFR, PDGF/PDGFR) but bevacizumab will be allowed.
• Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening:
• Hemoglobin ≥ 9.0 g/dl
• Absolute neutrophil count (ANC) ≥ 1,500/mm3
• Platelet count ≥ 100,000/μl
• Total bilirubin ≤ 1.5 x upper limit of normal
• ALT and AST ≤ 2.5 x upper limit of normal (\< 5 x upper limit of normal for patients with liver involvement of their cancer)
• Alkaline phosphatase ≤ 4 x upper limit of normal

You may not qualify if:

• History of cardiac disease: congestive heart failure \>NYHA class 2; active CAD (MI more than 6 months prior to study entry is allowed); cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted) or uncontrolled hypertension.
• Known history of HIV infection or chronic hepatitis B or C
• Active clinically serious infections (\> grade 2 NCI-CTC version 4.02)
• Prior clinical or radiological evidence of CNS metastases including previously treated, resected, or asymptomatic brain lesions or leptomeningeal involvement by contrast enhanced head CT scan or MRI
• Patients with seizure disorder requiring medication (such as steroids or anti-epileptics)
• History of organ allograft
• Patients with evidence or history of bleeding diathesis
• Patients undergoing renal dialysis
• Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumours \[Ta, Tis \& T1\] or any cancer curatively treated \> 3 years prior to study entry.
• Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Women enrolled in this trial must use adequate barrier birth control measures during the course of the trial.
• Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
• Any condition that is unstable or could jeopardise the safety of the patient and their compliance in the study
• Patients unable to swallow oral medications.
• Patients with intolerance to Paclitaxel.
• Excluded therapies and medications, previous and concomitant:

Sponsors & Collaborators

• Gesellschaft fur Medizinische Innovation - Hamatologie und Onkologie mbH: lead
• iOMEDICO AG: collaborator

Study Sites (1)

Germany Multiple Sites All Over Germany Recruiting Multiple Sites, Germany Contact: iOMEDICO AG

Freiburg im Breisgau, 79108, Germany

Location

Related Publications (3)

• Seidman AD, Berry D, Cirrincione C, Harris L, Muss H, Marcom PK, Gipson G, Burstein H, Lake D, Shapiro CL, Ungaro P, Norton L, Winer E, Hudis C. Randomized phase III trial of weekly compared with every-3-weeks paclitaxel for metastatic breast cancer, with trastuzumab for all HER-2 overexpressors and random assignment to trastuzumab or not in HER-2 nonoverexpressors: final results of Cancer and Leukemia Group B protocol 9840. J Clin Oncol. 2008 Apr 1;26(10):1642-9. doi: 10.1200/JCO.2007.11.6699.

  PMID: 18375893 BACKGROUND

• Gradishar W, Kaklamani V, Prasad Sahoo T. A double-blind, randomized, placebo-controlled, Phase 2b study evaluating the efficacy and safety of sorafenib (SOR) in combination with Paclitaxel (PAC) as a first-line therapy in patients with locally recurrent or metastatic breast cancer. Presented at : 32nd Annual San Antonio Breast Cancer Symposium. 2009 Dez 10;(Abstract 44).

  BACKGROUND

• Decker T, Overkamp F, Rosel S, Nusch A, Gohler T, Indorf M, Sahlmann J, Trarbach T. A randomized phase II study of paclitaxel alone versus paclitaxel plus sorafenib in second- and third-line treatment of patients with HER2-negative metastatic breast cancer (PASO). BMC Cancer. 2017 Jul 25;17(1):499. doi: 10.1186/s12885-017-3492-1.

  PMID: 28743247 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Paclitaxel; Sorafenib

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; Phenylurea Compounds; Urea; Amides; Benzene Derivatives; Hydrocarbons, Aromatic; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Friedrich Overkamp, Dr. med.

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: March 17, 2011
• First Posted: March 22, 2011
• Study Start: July 1, 2010
• Primary Completion: August 31, 2014
• Study Completion: August 31, 2014
• Last Updated: February 20, 2017

Record last verified: 2014-07

Locations

DE (1)