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Trial record 2 of 30 for:    celgene abi-007 | Recruiting, Not yet recruiting, Available Studies

NAPAGE: NAb-PAclitaxel and GEmcitabine in Advanced Soft Tissue Sarcoma

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ClinicalTrials.gov Identifier: NCT03524898
Recruitment Status : Not yet recruiting
First Posted : May 15, 2018
Last Update Posted : May 15, 2018
Sponsor:
Information provided by (Responsible Party):
Swiss Group for Clinical Cancer Research

Brief Summary:

A clinical trial with biweekly regimen of gemcitabine and nab-paclitaxel for Soft tissue sarcomas (STSs).

A Promising antitumor activity in patients with metastatic STS has been reported with gemcitabine alone or in combination with taxanes including docetaxel and paclitaxel in pre-treated patients.

Nab-paclitaxel is a 130-nm albumin-bound formulation of paclitaxel particles (Celgene, Summit, NJ) which was designed to eliminate the toxicities associated with Cremophor®-EL. Nab-paclitaxel at equal dose of paclitaxel showed increased antitumor activity, enhanced endothelial cell transport and 33% higher intra-tumor paclitaxel concentration in preclinical models of solid tumor xenografts promising an advantageous pharmacokinetic profile In sarcoma, nab-paclitaxel demonstrated preclinical anti-tumor activity in rhabdomyosarcoma xenograft model. Local relapsed tumors following paclitaxel treatment proved to be paclitaxel-resistant but remained responsive to nab-paclitaxel.

These findings provide the rationale for further evaluation of nab-paclitaxel in combination with gemcitabine for soft tissue sarcoma treatment.


Condition or disease Intervention/treatment Phase
Soft Tissue Sarcoma Drug: Nab-Paclitaxel Drug: gemcitabine Phase 1 Phase 2

Detailed Description:

Soft tissue sarcomas (STSs) account for 1% of all human cancers and consist of at least 50 different histological subtypes which have different clinical behavior and response to chemotherapy. Patients with advanced disease (locally advanced or metastatic) have a somber prognosis with a median OS between 12 and 15 months.

Palliative chemotherapy is the mainstay of treatment in the metastatic setting, although in a small subset with limited metastases local treatment may be curative. First-line treatment for advanced soft-tissue sarcoma includes doxorubicin hydrochloride, alone or in combination with other chemotherapy agents (e.g., ifosfamide), or olaratumab. Beyond first line several agents have shown activity, including gemcitabine/docetaxel, trabectedin and pazopanib, though no standard regimen has been established.

Promising antitumor activity in patients with metastatic STS has been reported with gemcitabine alone or in combination with taxanes including docetaxel and paclitaxel in pre-treated patients.

Nab-paclitaxel is a 130-nm albumin-bound formulation of paclitaxel particles (Abraxane®, Celgene, Summit, NJ) which was designed to eliminate the toxicities associated with Cremophor EL®. Nab-paclitaxel at equal dose of paclitaxel showed increased antitumor activity, enhanced endothelial cell transport and 33% higher intra-tumor paclitaxel concentration in preclinical models of solid tumor xenografts promising an advantageous pharmacokinetic profile In sarcoma, nab-paclitaxel demonstrated preclinical antitumor activity in rhabdomyosarcoma xenograft model. Local relapsed tumors following paclitaxel treatment proved to be paclitaxel-resistant but remained responsive to nab-paclitaxel.

These findings provide the rationale for further evaluation of nab-paclitaxel in combination with gemcitabine for soft tissue sarcoma treatment.

Phase Ib objective:

  • To assess the safety and feasibility of combining nab-paclitaxel and gemcitabine

Phase II objective:

  • To determine whether or not gemcitabine/nab-paclitaxel regimen exhibits antitumor activity that is worth testing further in STS.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Intervention Model: Single Group Assignment
Intervention Model Description: This is a single-arm phase Ib/IIa multi-center study in patients with locally advanced or metastatic soft tissue sarcoma who have received first line or second line chemotherapy with no response or with evidence of disease progression.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: NAPAGE: NAb-PAclitaxel and GEmcitabine in Advanced Soft Tissue Sarcoma. A Multicenter Open-label Single Arm Phase Ib/IIa Trial
Estimated Study Start Date : August 2018
Estimated Primary Completion Date : October 2021
Estimated Study Completion Date : October 2022


Arm Intervention/treatment
Experimental: nab-paclitaxel and gemcitabine
Treatment consists of the combination treatment of nab-paclitaxel and gemcitabine, which is given every 2 weeks during 28-day cycle intervals until disease progression.
Drug: Nab-Paclitaxel
150 mg/m2 / 125 mg/m2
Other Name: Abraxane
Drug: gemcitabine
1000 mg/m2



Primary Outcome Measures :
  1. Phase I: Dose-limiting toxicity (DLT) [ Time Frame: during the first cycle of treatment (28 days) ]
    DLT is defined as any of the following adverse events (AEs) occurring during the first cycle of treatment and regarded by the investigators and/or the Sponsor to be related to nab-paclitaxel and/or gemcitabine (AEs not related to the IMPs are not regarded as DLT)

  2. Phase II: Progression-free rate (PFR) [ Time Frame: at 12 weeks after registration ]

    PFR at 12 weeks after registration determined by the percentage of progression-free patients at 12 weeks. Progression is defined as one of the following events (whichever occurs first):

    • Progressive disease (PD) assessed according to the RECIST v1.1 before week 13 (allowed is a 1 week delay in the tumor assessment at week 12).
    • Death due to any cause up to week 12.
    • Start of second line treatment before week 12.
    • No tumor assessment after week 11 without subsequent treatment which shows stabilization or response.


Secondary Outcome Measures :
  1. Phase I: PFR 12 weeks [ Time Frame: at 12 weeks after registration ]
  2. Phase I: Best response assessed according to RECIST v1.1 [ Time Frame: assessed for up to 5 years after patient registration ]
  3. Phase I: Adverse events (AEs), assessed according to NCI CTCAE v4.03 [ Time Frame: assessed for up to 5 years after patient registration ]
  4. Phase II: Progression-free survival (PFS) [ Time Frame: assessed for up to 5 years after patient registration ]

    PFS defined as the time from registration until progression according to RECIST v1.1 or death from any cause, whichever occurs first.

    Patients without an event at the time of analysis and patients starting a new anticancer therapy in the absence of an event will be censored at the date of the last tumor assessment before the start of the new therapy, if any.


  5. Phase II: Overall Survival (OS) [ Time Frame: assessed for up to 5 years after patient registration ]
    OS defined as the time from registration until death from any cause. Patients without an event at the time of analysis will be censored at the date they were last known to be alive.

  6. Phase II: Best response assessed according to RECIST v1.1 [ Time Frame: assessed for up to 5 years after patient registration ]
  7. Phase II: AEs, assessed according to NCI CTCAE v4.03 [ Time Frame: from registration until 28 days after administration of the last dose of trial treatment ]
  8. Phase II: Symptom-related quality of life assessed by questionnaires [ Time Frame: assessed for up to 5 years after patient registration ]
    Symptom-related quality of life will be assessed with the M.D. Anderson Symptom Inventory (MDASI), which measures the severity of 13 cancer-related symptoms and their impact on six dimensions of daily life at their worst in the last 24 hours on a 0-10 numerical rating scale, with 0 being "not present" and 10 being "as bad as you can imagine."

  9. Phase II: Nab-paclitaxel related sensory neuropathy assessed by questionnaires [ Time Frame: assessed for up to 5 years after patient registration ]
    To address an important side-effect of nab-paclitaxel, sensory neuropathy will be assessed by the 4-item subscale of the FACT/GOG-Ntx (Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity), which measures the severity of sensory neuropathy in the last 7 days on a 0-4 numerical rating scale, with 0 being "not at all" and 4 being "very much."



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

Inclusion Criteria:

  • Histologically confirmed locally minimum grade 2 advanced or metastatic STS refractory to chemotherapy and not suitable for local treatment.
  • Minimum one line and maximum 2 lines of previous chemotherapy for advanced/metastatic STS
  • Measurable disease according to RECIST v1.1
  • Age ≥ 18 years
  • WHO performance status 0-2
  • Adequate hematological, hepatic and renal function
  • Negative pregnancy test
  • Effective method of birth control
  • Peripheral neuropathy at enrolment must be ≤ grade 1

Exclusion Criteria:

  • Uncontrolled CNS metastases
  • Previous or concomitant malignancy diagnosed within 3 years
  • More than 2 lines of previous systemic treatment for STS
  • Previous treatment with gemcitabine and/or nab-paclitaxel or other taxanes
  • Radiotherapy within 4 weeks prior to registration
  • Concurrent or recent treatment with any other experimental drug
  • Concomitant use of other anti-cancer drugs
  • Severe or uncontrolled cardiovascular disease
  • History of cerebrovascular accident or intracranial hemorrhage within 2 months prior to registration
  • Evidence of active, noninfectious pneumonitis or history of interstitial lung disease
  • Known history of human immunodeficiency virus (HIV) or active chronic Hepatitis C or Hepatitis B Virus infection or any uncontrolled active systemic infection
  • Any concomitant drugs contraindicated for use with the trial drugs according to the approved product information
  • Known hypersensitivity to the trial drug(s)

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): NCT03524898


Contacts
Contact: Nina Stojcheva, PhD +41 31 508 41 64 Nina.Stojcheva@sakk.ch

Locations
Switzerland
Universitaetsspital Basel
Basel, Switzerland, CH-4031
Istituto Oncologico della Svizzera Italiana
Bellinzona, Switzerland, 6500
Inselspital, Bern
Bern, Switzerland, CH-3010
Kantonsspital Graubünden
Chur, Switzerland, 7000
Hopital Cantonal Universitaire de Geneve
Geneva, Switzerland, CH-1211
CHUV - Swiss Cancer Center Lausanne Not yet recruiting
Lausanne, Switzerland, 1011
Contact: Antonia Digklia, MD    41 21 314 79 28    Antonia.Digklia@chuv.ch   
Principal Investigator: Antonia Digklia, MD         
Kantonsspital St. Gallen
St. Gallen, Switzerland, 9007
UniversitaetsSpital Zuerich
Zurich, Switzerland, CH-8091
Sponsors and Collaborators
Swiss Group for Clinical Cancer Research
Investigators
Study Chair: Antonia Digklia, MD Département d'Oncologie CHUV , Lausanne
Study Chair: Christian Rothermundt, MD Cantonal Hospital of St. Gallen

Responsible Party: Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier: NCT03524898     History of Changes
Other Study ID Numbers: SAKK 57/16
First Posted: May 15, 2018    Key Record Dates
Last Update Posted: May 15, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Swiss Group for Clinical Cancer Research:
Nab-Paclitaxel
Gemcitabine
Advanced soft tissue sarcoma
Cancer
Sarcoma
Abraxane®

Additional relevant MeSH terms:
Paclitaxel
Albumin-Bound Paclitaxel
Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Gemcitabine
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs