Eribulin Mesylate and Irinotecan Hydrochloride in Treating Adolescent and Young Adult Patients with Relapsed or Refractory Solid Tumors
This phase I/Ib trial studies the side effects and best dose of eribulin mesylate when given together with irinotecan hydrochloride in treating adolescent and young adults with solid tumors that are no longer responding to treatment or have spread to other places in the body. Eribulin mesylate may stop the growth of tumor cells by blocking microtubules needed for cell growth. Drugs used in chemotherapy, such as irinotecan 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. Giving eribulin mesylate and irinotecan hydrochloride may work better in treating patients with relapsed or refractory solid tumors.
Inclusion Criteria
- Patients must have a histologically confirmed solid tumor malignancy at either original diagnosis or relapse for which no curative therapy exists, and which has either recurred or progressed after at least one prior systemic therapy; patients with primary brain tumors, or those with brain metastases at time of potential enrollment, are excluded; additionally, patients with gastrointestinal stomal tumors (GIST), alveolar soft part sarcoma, or dermatofibrosarcoma protuberans are excluded
- Patients must have either measurable or evaluable disease
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%); Note: patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purposes of assessing the performance score
- No limit is placed on the number of prior therapies; prior treatment with irinotecan or eribulin is allowed, although patients must not have received co-administration of eribulin and irinotecan and must not have had disease progression while receiving either eribulin or irinotecan; patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study * Must not have received within three weeks of start date of this protocol chemotherapy; six weeks is required after administration of nitrosourea agents * At least 7 days since the completion of therapy with a growth factor or at least 14 days for a long-acting growth factor (e.g. pegfilgrastim) * At least 7 days or 3 half-lives since the completion of therapy with a biologic agent, whichever is longer; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are expected to occur; the duration of this interval must be discussed with the principal investigator (PI) of the study * At least 6 weeks since the completion of any type of immunotherapy (e.g. tumor vaccines) * At least 3 half-lives must have elapsed since prior therapy that included a monoclonal antibody * Radiotherapy: >= 2 weeks for local palliative radiotherapy (XRT) (small port); >= 6 months must have elapsed if prior total body irradiation (TBI), craniospinal XRT; >= 3 months must have elapsed if >= 50% radiation of pelvis; >= 6 weeks must have elapsed if therapeutic doses of metaiodobenzylguanidine (MIBG) or other substantial bone marrow (BM) irradiation was given * Allogeneic and autologous hematopoietic stem cell transplant (HSCT) will be allowed, if there is no evidence of active graft vs. host disease and >= 2 months must have elapsed since infusion; patients must not be on systemic immunosuppression
- Absolute neutrophil count >= 1,000/mcL
- Platelets >= 100,000/mcL (transfusion independent, defined as not receiving platelet transfusions within a 7-day period prior to enrollment)
- Hemoglobin >= 8.0 g/dl (may receive red blood cell [RBC] transfusions)
- Total bilirubin =< 1.5 x institutional upper limit of normal for age
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) / alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
- Albumin >= 2 g/dl
- Creatinine within normal institutional limits for age OR creatinine clearance >= 70 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
- Electrocardiography (EKG) corrected QT (QTc) < 480 msec (Common Terminology Criteria for Adverse Events [CTCAE] grade 2)
- Males and females of child-bearing potential 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 and for 4 months after the last dose of study chemotherapy
- All patients >= 18 years must sign a written informed consent; patients < 18 years old must provide assent, and the parent or legal guardian must sign the written informed consent
Exclusion Criteria
- Patients who are pregnant or breast-feeding are not eligible for this study; negative pregnancy tests must be obtained in female patients who are postmenarchal
- Major surgery within 14 days prior to start of treatment; no time limitations after minor surgery (e.g.: core biopsy or central line placement)
- Current evidence of GIST, alveolar soft part sarcoma, or dermatofibrosarcoma
- Concomitant medications: * Growth factors that support platelet or white cell number or function must not have been administered within the 7 days prior to enrollment (14 days if pegfilgrastim) * Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for the 7 days prior to enrollment are not eligible * Patients who are currently receiving another investigational drug are not eligible * Patients who are currently receiving other anti-cancer agents are not eligible * Patients who are currently receiving the enzyme inducing anticonvulsants: phenytoin, phenobarbital, carbamazepine, oxcarbazepine are not eligible; patients who are currently taking rifampin, voriconazole, itraconazole, ketoconazole, aprepitant, or St. John’s Wort are not eligible * Use of warfarin is not allowed while on study; patients already on warfarin should use alternative anticoagulants while on this study; warfarin must not have been administered within 7 days of starting protocol therapy * Patients receiving medications that prolong the QTc
- Patients who have an uncontrolled infection, or who are currently receiving treatment for Clostridium (C) difficile infection
- Patients with a history of allergic reactions attributed to eribulin or irinotecan
- Patients with documented allergy to cephalosporins
- Patients with central nervous system (CNS) tumors or known brain metastases
- Patients with known metastatic tumor in the bone marrow
- Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study
- Uncontrolled intercurrent illness that would limit compliance with study requirements
- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT02596503.
PRIMARY OBJECTIVES:
I. To estimate the recommended phase II dose (RP2D) of eribulin mesylate (eribulin) in combination with fixed-dose oral irinotecan hydrochloride (irinotecan) in adolescents and young adults with relapsed/refractory solid tumors.
SECONDARY OBJECTIVES:
I. To evaluate the toxicity profile of this combination and define the dose-limiting toxicities.
II. To characterize the pharmacokinetics of eribulin in patients receiving oral irinotecan.
III. To determine the antitumor activity of this drug combination within the confines of a phase I/Ib trial.
OUTLINE: This is a dose escalation study of eribulin mesylate.
Patients receive eribulin mesylate intravenously (IV) over 2-5 minutes on days 1 and 8 and irinotecan hydrochloride orally (PO) on days 1-5. Treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days.
Trial PhasePhase I
Trial Typetreatment
Lead OrganizationChildren's Hospital Colorado
Principal InvestigatorCarrye Rudolph Cost
- Primary ID15-0659
- Secondary IDsNCI-2016-00347, NCT02318589, ERIB-IRINO-SLDTMR, MCC-15-0593-F6A
- ClinicalTrials.gov IDNCT02596503