Nab-Paclitaxel and Gemcitabine Hydrochloride in Treating Teenagers or Young Adults with Recurrent or Refractory Osteosarcoma, Ewing Sarcoma, Rhabdomyosarcoma, or Soft Tissue Sarcoma

Status: Active

Description

This phase II trial studies how well nab-paclitaxel and gemcitabine hydrochloride work in treating teenagers or young adults with osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, or soft tissue sarcoma that has come back or does not respond to treatment. Drugs used in chemotherapy, such as nab-paclitaxel and gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Eligibility Criteria

Inclusion Criteria

  • Have had a histologic diagnosis of osteosarcoma, Ewing sarcoma, or rhabdomyosarcoma or non-rhabdomyosarcoma soft tissue sarcoma either at diagnosis or relapse * Patients must have experienced relapse after front-line therapy, or have had documented disease progression during front-line therapy
  • All patients must have measurable disease that can be assessed using RECIST 1.1 criteria, which is defined as the presence of at least one lesion on magnetic resonance imaging (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
  • Patients 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, patients must have recovered from the acute toxic effects of all prior treatment * Patients must not have received prior therapy with either gemcitabine or nab-paclitaxel * Myelosuppressive chemotherapy: patients must not have received myelosuppressive chemotherapy within 3 weeks of protocol therapy on this study * 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 * Biologic (anti-neoplastic agent): 7 days must have elapsed from the start of protocol therapy since the completion of therapy with a biologic agent * Monoclonal antibodies: 3 half-lives must have elapsed from the start of protocol therapy since prior therapy that included a monoclonal antibody * Radiotherapy: 2 weeks must have elapsed from the start of protocol therapy since local palliative radiation therapy (XRT) (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 * Stem cell transplant or rescue: no evidence of active graft versus (vs.) host disease and 2 months must have elapsed from the start of protocol therapy since transplant
  • Karnofsky performance score must be >= 60
  • Absolute neutrophil count >= 1,000/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin within normal institutional limits
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 x upper limit of normal
  • Serum creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • Neuropathy: patients must have =< grade 1 neuropathy at enrollment
  • Central nervous system (CNS) metastases: patients with known central nervous system 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 (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of gemcitabine and nab-paclitaxel administration
  • Consent: patients must have the ability to understand and the willingness to sign a written informed consent or assent document

Exclusion Criteria

  • Patients who are receiving any other investigational agents are ineligible
  • Patients must not be receiving any additional medicines being given for the specific purpose of treating cancer
  • Patients with a history of allergic reactions attributed to docetaxel or paclitaxel are ineligible
  • Concomitant medications: the following medicines should be avoided on this study: * Inhibitors: ketoconazole and other imidazole antifungals, erythromycin, fluoxetine, gemfibrozil, cimetidine, ritonavir, saquinavir, indinavir, and nelfinavir * Inducers: rifampicin, carbamazepine, phenytoin, efavirenz, and nevirapine * Patients receiving any of the above medications are ineligible
  • Patients 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
  • Pregnancy and breastfeeding: pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated on this study
  • Human immunodeficiency virus (HIV) infection: HIV-positive patients on combination antiretroviral therapy are ineligible; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
  • Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible

Locations & Contacts

California

Los Angeles
Children's Hospital Los Angeles
Status: Active
Contact: Leo Mascarenhas
Phone: 323-361-2529
Email: lmascarenhas@chla.usc.edu

Connecticut

Hartford
Connecticut Children's Medical Center
Status: Active
Contact: Michael Scott Isakoff
Phone: 860-545-9637
Email: misakoff@ccmckids.org

Delaware

Wilmington
Alfred I duPont Hospital for Children
Status: Approved
Contact: Emi H. Caywood
Phone: 302-651-5500
Email: Emi.Caywood@nemours.org

Florida

Gainesville
University of Florida Health Science Center - Gainesville
Status: Active
Contact: Joanne Pigues Lagmay
Phone: 352-273-9120
Email: jplagmay@peds.ufl.edu
Jacksonville
Nemours Children's Clinic-Jacksonville
Status: Active
Contact: Eric S. Sandler
Phone: 904-697-3793
Email: esandler@nemours.org
Miami
Jackson Memorial Hospital-Holtz Children's Hospital
Status: Active
Contact: Matteo Maria Trucco
Phone: 305-243-4830
Email: mxt722@med.miami.edu
Saint Petersburg
Johns Hopkins All Children's Hospital
Status: Active
Contact: Damon Russell Reed
Phone: 727-767-4176
Email: dreed29@jhmi.edu
Tampa
Moffitt Cancer Center
Status: Active
Contact: Damon Russell Reed
Phone: 813-745-2297
Email: damon.reed@moffitt.org
Tampa General Hospital
Status: Approved
Contact: Cameron K. Tebbi
Phone: 813-259-8700
Email: ctebbi@health.usf.edu

Georgia

Atlanta
Children's Healthcare of Atlanta - Egleston
Status: Approved
Contact: Hong (Julie) Yin
Phone: 404-785-5437
Email: hong.yin@choa.org

Kentucky

Lexington
University of Kentucky / Markey Cancer Center
Status: Active
Contact: Lars Martin Wagner
Phone: 859-218-0931
Email: lars.wagner@uky.edu

Maryland

Baltimore
Johns Hopkins University / Sidney Kimmel Cancer Center
Status: Active
Contact: Christine Anne Pratilas
Phone: 443-287-8623
Email: cpratil1@jhmi.edu

New York

Bronx
Montefiore Medical Center - Moses Campus
Status: Approved
Contact: Richard G. Gorlick
Phone: 718-741-2342
Email: RGORLICK@montefiore.org

North Carolina

Chapel Hill
UNC Lineberger Comprehensive Cancer Center
Status: Active
Contact: Patrick Andrew Thompson
Email: patom@email.unc.edu
Charlotte
Carolinas Medical Center / Levine Cancer Institute
Status: Active
Contact: Javier E. Oesterheld
Phone: 704-381-9900
Email: Javier.oesterheld@carolinashealthcare.org

Ohio

Columbus
Nationwide Children's Hospital
Status: Active
Contact: Bhuvana Anantha Setty
Phone: 614-722-3553
Email: Bhuvana.Setty@nationwidechildrens.org

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To assess the antitumor activity of nab-paclitaxel combined with gemcitabine hydrochloride (gemcitabine) in patients with relapsed or refractory osteosarcoma, Ewing sarcoma, rhabdomyosarcoma and other soft tissue sarcoma using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria and progression-free survival.

SECONDARY OBJECTIVES:

I. To describe the toxicities of the combination in adolescents and young adults with relapsed/refractory sarcoma.

II. To assess the immunohistochemical expression of SPARC and CAV-1 in archival tumor tissue, and compare results with treatment response.

III. To evaluate a set of radiomic biomarkers calculated from baseline and post-therapy computed tomography (CT) scans, and compare results with treatment response.

IV. To quantify circulating tumor cells (CTC) in patients with recurrent or refractory sarcomas, and determine if CTC changes reflect response to therapy or predict risk of progression.

OUTLINE:

Patients receive nab-paclitaxel intravenously (IV) over 30 minutes and gemcitabine hydrochloride IV over 90 minutes on days 1, 8, and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days and then every 3 months.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
Moffitt Cancer Center

Principal Investigator
Javier E. Oesterheld

Trial IDs

Primary ID MCC-18613
Secondary IDs NCI-2016-01837
Clinicaltrials.gov ID NCT02945800