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

NCT03524898 | Terminated Phase 1 DMC

• 1 other identifier: SAKK 57/16 - NAPAGE
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 8

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.

Conditions

Soft Tissue Sarcoma

Keywords

Nab-Paclitaxel; Gemcitabine; Advanced soft tissue sarcoma; Cancer; Sarcoma; Abraxane®

Outcome Measures

Primary Outcomes (2)

• Phase I: Dose-limiting toxicity (DLT)

  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)

  during the first cycle of treatment (28 days)

• Phase II: Progression-free rate (PFR)

  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.

  at 12 weeks after registration

Secondary Outcomes (9)

• Phase I: PFR 12 weeks

  at 12 weeks after registration

• Phase I: Best response assessed according to RECIST v1.1

  assessed for up to 5 years after patient registration

• Phase I: Adverse events (AEs), assessed according to NCI CTCAE v4.03

  assessed for up to 5 years after patient registration

• Phase II: Progression-free survival (PFS)

  assessed for up to 5 years after patient registration

• Phase II: Overall Survival (OS)

  assessed for up to 5 years after patient registration

Study Arms (1)

nab-paclitaxel and gemcitabine

EXPERIMENTAL

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; Drug: gemcitabine

Interventions

Nab-Paclitaxel DRUG

150 mg/m2 / 125 mg/m2

Also known as: Abraxane

nab-paclitaxel and gemcitabine

gemcitabine DRUG

1000 mg/m2

nab-paclitaxel and gemcitabine

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed minimum grade 2, locally 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

You may not qualify if:

• Uncontrolled CNS metastases
• Previous or concomitant malignancy diagnosed within 3 years
• More than 2 lines of previous systemic treatment for STS
• Previous sarcoma 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)

Sponsors & Collaborators

• Swiss Cancer Institute: lead

Study Sites (8)

Universitaetsspital Basel

Basel, CH-4031, Switzerland

Location

Istituto Oncologico della Svizzera Italiana

Bellinzona, 6500, Switzerland

Location

Inselspital, Bern

Bern, CH-3010, Switzerland

Location

Kantonsspital Graubünden

Chur, 7000, Switzerland

Location

Hopital Cantonal Universitaire de Geneve

Geneva, CH-1211, Switzerland

Location

CHUV - Swiss Cancer Center Lausanne

Lausanne, 1011, Switzerland

Location

Kantonsspital St. Gallen

Sankt Gallen, 9007, Switzerland

Location

UniversitätsSpital Zürich

Zurich, 8091, Switzerland

Location

MeSH Terms

Conditions

Sarcoma; Neoplasms

Interventions

130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel; Gemcitabine

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Antonia Digklia, MD

  Département d'Oncologie CHUV , Lausanne

  STUDY CHAIR

• Christian Rothermundt, MD

  Cantonal Hospital of St. Gallen

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: April 24, 2018
• First Posted: May 15, 2018
• Study Start: October 2, 2018
• Primary Completion: February 15, 2022
• Study Completion: February 15, 2022
• Last Updated: September 28, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

CH (8)