Nab-Paclitaxel and Gemcitabine for Recurrent/Refractory Sarcoma

Phase II Study of Nab-Paclitaxel in Combination With Gemcitabine for Treatment of Recurrent/Refractory Sarcoma in Teenagers and Young Adults

The purpose of this study is to see if nab-paclitaxel combined with gemcitabine prevents the formation or growth of tumors in participants with relapsed or refractory osteosarcoma, Ewing sarcoma, rhabdomyosarcoma and other soft tissue sarcoma and to measure the length of time during and after treatment that their disease does not get worse. Researchers also want to find out if nab-paclitaxel combined with gemcitabine is safe and tolerable.

Study Overview

• Status: Completed
• Conditions: Soft Tissue Sarcoma; Osteosarcoma; Ewing Sarcoma; Rhabdomyosarcoma
• Intervention / Treatment: Drug: nab-Paclitaxel; Drug: Gemcitabine

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham Comprehensive Cancer Center
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
  • Connecticut
    • Hartford, Connecticut, United States, 06103
      • Connecticut Children's Medical Center
  • Delaware
    • Wilmington, Delaware, United States, 19603
      • A.I. duPont Hospital for Children, Delaware - Nemours
  • Florida
    • Gainesville, Florida, United States, 32608
      • Shand's Hospital for Children at the University of Florida
    • Jacksonville, Florida, United States, 32207
      • Nemours Children's Clinic
    • Miami, Florida, United States, 33136
      • Holtz Children's Hospital at the University of Miami
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center and Research Institute, Coordinating Center
  • Kentucky
    • Lexington, Kentucky, United States, 40506
      • University of Kentucky
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina at Chapel Hill
    • Charlotte, North Carolina, United States, 28303
      • Carolinas Medical Center, Levine Cancer Institute
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt - Ingram Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 30 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants must be age ≥ 3 and ≤ 30 years, and have had a histologic diagnosis of osteosarcoma, Ewing sarcoma, or rhabdomyosarcoma or non-rhabdomyosarcoma soft tissue sarcoma either at diagnosis or relapse. Must have experienced relapse after front-line therapy, or have had documented disease progression during front-line therapy.
• Must have measurable disease that can be assessed using Response Evaluation in Solid Tumors (RECIST) 1.1, defined as the presence of at least one lesion on MRI or CT scan that can be accurately measured with the longest diameter of 10 mm in at least one dimension. For this phase II trial, patients with disease limited to bone or marrow metastases are NOT eligible, as disease at these sites cannot be assessed by RECIST 1.1 criteria.
• Must have relapsed or refractory cancers for which there is no known curative option.
• Prior Therapy: There is no limit to the number of prior therapies provided all eligibility criteria are met. However, participants must have recovered from the acute toxic effects of all prior treatment. (A) Must not have received prior therapy with either gemcitabine or nab-paclitaxel. (B) Myelosuppressive chemotherapy: Must not have received myelosuppressive chemotherapy within 3 weeks of protocol therapy on this study. (C) Hematopoietic growth factors: 7 days must have elapsed from the start of protocol therapy since the completion of therapy with filgrastim, and 14 days must have elapsed from the start of protocol therapy after receiving pegfilgrastim. (D) Biologic (anti-neoplastic agent): 7 day must have elapsed from the start of protocol therapy since the completion of therapy with a biologic agent. (E) Monoclonal antibodies: 3 half-lives must have elapsed from the start of protocol therapy since prior therapy that included a monoclonal antibody. (F) Radiotherapy: 2 weeks must have elapsed from the start of protocol therapy since local palliative radiotherapy (small port); 3 months must have elapsed if 50% radiation of pelvis; 6 weeks must have elapsed if other substantial bone marrow irradiation was given. (G) Stem Cell Transplant or Rescue: No evidence of active graft vs. host disease and 2 months must have elapsed from the start of protocol therapy since transplant.
• Karnofsky performance score must be ≥ 60
• Must have organ and marrow function
• Neuropathy: Must have ≤ grade 1 neuropathy at enrollment
• Central nervous system (CNS) Metastases: Potential participants with known CNS metastases are excluded unless treated surgically or with radiotherapy and stable with no recurrent lesions for at least 3 months from the start of protocol therapy.
• Contraception: Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation. Men treated or enrolled on this protocol must also agree to use adequate contraception 4 months after completion of gemcitabine and nab-paclitaxel administration.
• Consent: Participants must have the ability to understand and the willingness to sign a written informed consent or assent document.

Exclusion Criteria:

• Potential participants who are receiving any other investigational agents
• Must not be receiving any additional medicines being given for the specific purpose of treating cancer
• A history of allergic reactions attributed to docetaxel or paclitaxel
• Concomitant Medications: The metabolism of paclitaxel is catalyzed by CYP2C8 and CYP3A4. The following medicines should be avoided on this study because of their ability to inhibit or induce with CYP2C8 or CYP3A4: A) Inhibitors: ketoconazole and other imidazole antifungals, erythromycin, fluoxetine, gemfibrozil, cimetidine, ritonavir, saquinavir, indinavir, and nelfinavir. B) Inducers: Rifampicin, carbamazepine, phenytoin, efavirenz, and nevirapine. C) Potential participants receiving any of the above medications are ineligible.
• Potential participants are ineligible if they have uncontrolled intercurrent illness including, but not limited to: ongoing or active infection; symptomatic congestive heart failure; unstable angina pectoris; cardiac arrhythmia; psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant or breastfeeding
• HIV Infection: HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with the study medications.
• Anyone who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Combination Therapy; Participants will receive nab-Paclitaxel and Gemcitabine on days 1, 8, and 15 of each 28 day cycle, for up to 12 cycles.	Drug: nab-Paclitaxel; nab-Paclitaxel: 125 mg/m^2 intravenously (IV); Other Names: Abraxane; Drug: Gemcitabine; Gemcitabine: 1000 mg/m^2 intravenously (IV); Other Names: Gemzar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rate	Treatment response will be assessed with the most relevant imaging studies (e.g., CT or MRI) after every two cycles. Standard Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 will be used to assess responses. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm (<1 cm). Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.	13 months
Progression Free Survival (PFS)	Progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm (0.5 cm).	13 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of Study Treatment Related Adverse Events	Adverse Events (AEs) and Serious Adverse Events (SAEs) according to Common Terminology Criteria for Adverse Events (CTCAE) V4.0, deemed to be caused by study treatment.	13 months

Collaborators and Investigators

• Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Collaborators: National Pediatric Cancer Foundation
• Investigators: Principal Investigator: Javier E. Oesterheld, M.D., Carolinas Medical Center, Levine Cancer Institute

Publications and helpful links

General Publications

• Hattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14.

Helpful Links

• Moffitt Cancer Center Clinical Trials website

Study record dates

Study Major Dates

• Study Start (Actual): October 25, 2016
• Primary Completion (Actual): November 19, 2024
• Study Completion (Actual): February 17, 2025

Study Registration Dates

• First Submitted: October 25, 2016
• First Submitted That Met QC Criteria: October 25, 2016
• First Posted (Estimated): October 26, 2016

Study Record Updates

• Last Update Posted (Actual): April 2, 2026
• Last Update Submitted That Met QC Criteria: March 31, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: pediatric; relapsed; refractory; soft tissue; bones and joints; non-rhabdomyosarcoma soft tissue sarcoma
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease Attributes; Neoplasms by Histologic Type; Neoplasms, Connective and Soft Tissue; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Muscle Tissue; Myosarcoma; Pathological Conditions, Signs and Symptoms; Recurrence; Sarcoma, Ewing; Sarcoma; Rhabdomyosarcoma; Osteosarcoma; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Taxoids; Cyclodecanes; Diterpenes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Albumins; Paclitaxel; Albumin-Bound Paclitaxel; Gemcitabine; 130-nm albumin-bound paclitaxel
• Other Study ID Numbers: MCC-18613

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No