Nab-Paclitaxel and Gemcitabine Hydrochloride in Treating Teenagers or Young Adults with Recurrent or Refractory Osteosarcoma, Ewing Sarcoma, Rhabdomyosarcoma, or Soft Tissue Sarcoma
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.
- 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
- 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
Contact: Leo Mascarenhas
Contact: Michael Scott Isakoff
Contact: Emi H. Caywood
Contact: Joanne Pigues Lagmay
Contact: Eric S. Sandler
Contact: Matteo Maria Trucco
Contact: Damon Russell Reed
Contact: Damon Russell Reed
Contact: Cameron K. Tebbi
Contact: Hong (Julie) Yin
Contact: Lars Martin Wagner
Contact: Christine Anne Pratilas
Contact: Richard G. Gorlick
Contact: Patrick Andrew Thompson
Contact: Javier E. Oesterheld
Contact: Bhuvana Anantha Setty
Trial Objectives and Outline
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.
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.
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
Moffitt Cancer Center
Javier E. Oesterheld
Secondary IDs NCI-2016-01837
Clinicaltrials.gov ID NCT02945800