Clinical trial NCT02945800: Nab-Paclitaxel and Gemcitabine for Recurrent/Refractory Sarcoma
Official title: Phase II Study of Nab-Paclitaxel in Combination With Gemcitabine for Treatment of Recurrent/Refractory Sarcoma in Teenagers and Young Adults
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Osteosarcoma
Ewing Sarcoma
Rhabdomyosarcoma
Soft Tissue Sarcoma
Keywords: relapsed
refractory
soft tissue
bones and joints
non-rhabdomyosarcoma soft tissue sarcoma
pediatric
Lead sponsor: H. Lee Moffitt Cancer Center and Research Institute
Sponsor class: OTHER
Collaborators: name: National Pediatric Cancer Foundation
First posted: 2016-10-26
Enrollment: 59
Sex: ALL
Minimum age (years): 3
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Response Rate
timeFrame: 13 months
measure: Progression Free Survival (PFS)
timeFrame: 13 months
Secondary outcomes:
measure: Occurrence of Study Treatment Related Adverse Events
timeFrame: 13 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Comprehensive Cancer Center
state: Alabama
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Hartford
country: United States
facility: Connecticut Children's Medical Center
state: Connecticut
city: Wilmington
country: United States
facility: A.I. duPont Hospital for Children, Delaware - Nemours
state: Delaware
city: Gainesville
country: United States
facility: Shand's Hospital for Children at the University of Florida
state: Florida
city: Jacksonville
country: United States
facility: Nemours Children's Clinic
state: Florida
city: Miami
country: United States
facility: Holtz Children's Hospital at the University of Miami
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute, Coordinating Center
state: Florida
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Charlotte
country: United States
facility: Carolinas Medical Center, Levine Cancer Institute
state: North Carolina
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Nashville
country: United States
facility: Vanderbilt - Ingram Cancer Center
state: Tennessee
Study officials:
affiliation: Carolinas Medical Center, Levine Cancer Institute
name: Javier E. Oesterheld, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.