A Phase I/Ib Study of Eribulin in Combination with Oral Irinotecan for Adolescent and Young Adult Patients with Relapsed or Refractory Solid Tumors
Study ID: STU 092016-012
This Phase i trial will establish the recommended phase ii dose (RP2D) of eribulin in combination with fixed doses of oral irinotecan in adolescents and young adults with relapsed or refractory solid tumors. eribulin will be administered intravenously on days 1 and 8 of a 21-day cycle, while irinotecan will be administered orally on days 1-5. The oral antibiotic cefixime will be used to reduce irinotecan-associated diarrhea, starting two days prior to each cycle and continuing through day 8. Patients will be assigned an eribulin dose level at the time of enrollment using a 3 + 3 Phase i design, and there will be no intrapatient dose escalation. once the RP2D is defined, there will be 10 patients enrolled in a dose expansion cohort.
1. Patients must >= 13 and <= 30 years of age at the time of study entry. 2. 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 stromal tumor (GIST), alveolar soft part sarcoma, or dematofibrosarcoma protuberans are excluded. 3. Patients must have either measurable or evaluable disease. 4. Performance Level: 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. 5. Prior Therapy: 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. a. Myelosuppressive chemotherapy: Must not have received within three weeks of start date of this protocol chemotherapy; six weeks is required after administration of nitrosourea agents. b. Hematopoietic growth factors: 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) c. Biologic (anti-neoplastic agent): 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 PI of the study. d. Immunotherapy: At least 6 weeks since the completion of any type of immunotherapy (e.g. tumor vaccines). e. Monoclonal antibodies: At least 3 half-lives must have elapsed since prior therapy that included a monoclonal antibody. f. Radiotherapy: >= 2 weeks for local palliative external radiation therapy (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. g. Stem Cell Transplant or Rescue without TBI: Allogeneic and autologous hematopoietic stem cell transplantation (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. 6. Organ Function Requirements: Patients must have normal organ and marrow function as defined below. x Absolute neutrophil count >= 1,000/mcL x Platelets >= 100,000/mcL (transfusion independent, defined as not receiving platelet transfusions within a 7-day period prior to enrollment) x Hemoglobin >= 8.0 g/dl (may receive red blood cell (RBC) transfusions). x Total bilirubin <= 1.5 x institutional upper limit of normal for age x Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase (SGOT))/Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase (SGPT)) <= 2.5 x institutional upper limit of normal x Albumin >= 2 g/dl x Creatinine within normal institutional limits for age OR creatinine clearance >= 70 mL/min/1.73 m2 for patients with creatinine levels above institutional normal - Electrocardiogram (EKG) corrected QT interval (QTc) <= 480 msec (Common Terminology Criteria for Adverse Events (CTCAE) Grade 2) 7. Contraception: Because chemotherapeutic agents may be teratogenic, 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. 8. Informed Consent: 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.
- Cancer Related
- Healthy Volunteers
- UT Southwestern Principal Investigator
- Theodore W Laetsch
UNIVERSITY OF COLORADO DENVER