Phase I of Eribulin and Oral Irinotecan for Relapsed or Refractory Solid Tumors

Solid Tumor Clinical Trial

Official title:

A Phase I Study of Eribulin in Combination With Oral Irinotecan for Adolescent and Young Adult Patients With Relapsed or Refractory Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02318589
• Other study ID #: ERIB-IRINO-SLDTMR
• Status: Recruiting
• Phase: Phase 1
• First received: October 10, 2014
• Last updated: October 26, 2017
• Start date: August 2015
• Est. completion date: June 30, 2020

Study information

• Verified date: October 2017
• Source: University of Kentucky
• Contact: Tom Badgett, MD, PhD
• Email: tom.badgett[@]uky.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This Phase I trial will establish the recommended phase II dose 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. Patients will be assigned an eribulin dose level at the time of enrollment using a 3 + 3 Phase I design.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 18
• Est. completion date: June 30, 2020
• Est. primary completion date: June 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 15 Years to 39 Years

Eligibility

Inclusion Criteria:

• Patients must be >15 and < 40 years of age at the time of study entry

• Patients must have had a histologically confirmed solid tumor malignancy at either original diagnosis or relapse for which no curative therapy exists. Patients with primary brain tumors, or those with brain metastases at time of potential enrollment, are excluded

• Patients must have either measurable or evaluable disease

• Performance Level: ECOG performance status = 2 (Karnofsky =60%, see Appendix A). 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

• 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

• 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

• 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)

• Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent. 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 known to occur. The duration of this interval must be discussed with the PI of the study

• Immunotherapy: At least 6 weeks since the completion of any type of immunotherapy (e.g. tumor vaccines)

• Monoclonal antibodies: At least 3 half-lives must have elapsed since prior therapy that included a monoclonal antibody

• Radiotherapy: = 2 weeks for local palliative XRT (small port); = 6 months must have elapsed if prior TBI, craniospinal XRT; = 3 months must have elapsed if = 50% radiation of pelvis; = 6 weeks must have elapsed if therapeutic doses of MIBG or other substantial BM irradiation was given

• Stem Cell Transplant or Rescue without TBI: No evidence of active graft vs. host disease and = 2 months must have elapsed

• Organ Function Requirements: Patients must have normal organ and marrow function as defined below

• 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 RBC transfusions)

• Total bilirubin = 1.5 × institutional upper limit of normal for age

• AST(SGOT)/ALT(SGPT) = 2.5 × institutional upper limit of normal

• Albumin = 2 g/dl

• Creatinine within normal institutional limits for age OR

• creatinine clearance = 70 mL/min/1.73 m2 for patients with creatinine levels above institutional normal

• 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

• All patients > 18 years must sign a written informed consent. Patients < 18 years old must sign an assent document, and the parent or legal guardian must sign the written informed consent

Exclusion Criteria:

• Pregnancy or Breast-Feeding: Patients who are pregnant or breast-feeding are not eligible for this study due to the potential for fetal or teratogenic toxicities. Negative pregnancy tests must be obtained in female patients who are post-menarchal

• Concomitant Medications:

• Growth factor(s): 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)

• Corticosteroids: 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

• Investigational Drugs: Patients who are currently receiving another investigational drug are not eligible

• Anti-cancer Agents: Patients who are currently receiving other anti-cancer agents are not eligible

• Enzyme-inducing anticonvulsants or other medications: 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

• Anticoagulants: 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

• Infection: Patients who have an uncontrolled infection, or who are currently receiving treatment for C difficile infection

• Patients with a history of allergic reactions attributed to eribulin or irinotecan

• Patients with documented allergy to cephalosporins

• Patients with 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

• HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with eribulin and irinotecan. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy

Related Conditions & MeSH terms

• Solid Tumor

Intervention

Drug:
• Irinotecan + Eribulin
Patients receive Oral Irinotecan on days 1-5 and IV Eribulin on days 1 and 8 of a 21 day cycle in the absence of disease progression or unacceptable toxicity.

Locations

Country	Name	City	State
United States	University of Kentucky, Markey Cancer Center	Lexington	Kentucky

Sponsors (1)

Lead Sponsor	Collaborator
Tom Badgett

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recommended phase II dose of eribulin when used in combination with oral irinotecan	To estimate the recommended phase II dose of eribulin in combination with fixed-dose oral irinotecan in adolescents and young adults with relapsed/refractory solid tumors	21 days
Secondary	Grade and number of adverse events in patients receiving the combination of eribulin and oral irinotecan	To evaluate the toxicity profile of the drug combination using the number and grade and of adverse events reported using the CTCAE v4.0	21 days
Secondary	To characterize the pharmacokinetics of eribulin in patients receiving oral irinotecan by estimating several parameters including area under the concentration versus time curve, AUC, half-life, clearance, and Cmax.	To characterize the pharmacokinetics of eribulin in patients receiving oral irinotecan by estimating several parameters including area under the concentration versus time curve, AUC, half-life, clearance, and Cmax.	Cycle 1 days 1 and 8
Secondary	Antitumor effects based on RECIST 1.1 criteria	To estimate the antitumor effect of the drug combination using RECIST 1.1 criteria	Up to 1 year