Relapsed Solid TumorsPhase 1NCT02596503
A Study of Eribulin in Combination With Oral Irinotecan for Adolescent and Young Adult Patients With Relapsed or Refractory Solid Tumors
A Phase 1 study testing Eribulin, Irinotecan and Cefixime in people with Relapsed Solid Tumors and Refractory Solid Tumors, run by University of Colorado, Denver at 3 sites in United States.
Trial summary
This IND-exempt Phase I trial will establish the recommended Phase II (RP2D) dose of eribulin in combination with fixed doses of oral irinotecan in adolescents and young adults with relapsed or refractory solid tumors. Read more about this study
- Who is it for?
- Ages 13 to 30 years
- Conditions the study is for
- Relapsed Solid Tumors, Refractory Solid Tumors
- What is being tested?
- Eribulin, Irinotecan and Cefixime
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 3 sitesUnited States
- Study dates
- 21 Oct 2015to 24 Jan 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 13 to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patients must ≥13 and ≤30 years of age at the time of study entry
- 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 GIST, alveolar soft part sarcoma, or dematofibrosarcoma protuberans 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.
Show all 24Show fewer
- 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 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.
- 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: Allogeneic and autologous 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.
- 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 normal
- EKG QTc ≤480 msec (CTCAE Grade 2)
- 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.
- 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.
Who cannot join
- 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.
- Major surgery within 14 days prior to start of treatment. No time limitations after minor surgery (eg: core biopsy or central line placement)
- Current evidence of GIST, alveolar soft part sarcoma, or dermatofibrosarcoma
- 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.
Show all 19Show fewer
- 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.
- Medications that prolong the QTc:
- 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.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Children's Hospital Colorado
Aurora, Colorado, 80045
University of Texas, Southwestern Medical Center
Dallas, Texas
University of Kentucky
Lexington, Kentucky, 40536
About this study
Official title: A Phase I/II Study of Eribulin in Combination With Oral Irinotecan for Adolescent and Young Adult Patients With Relapsed or Refractory Solid Tumors
This IND-exempt Phase I trial will establish the recommended Phase II (RP2D) 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, and there will be no intrapatient dose escalation. Once the RP2D has been established, there will be up to 10 patients enrolled in a dose expansion cohort. In absence of disease progression or toxicity, subjects may receive up to 17 cycles of therapy.
- Conditions
- Relapsed Solid Tumors, Refractory Solid Tumors
- Being tested
- Eribulin, Irinotecan, Cefixime
- Keywords
- young adults, adolescents
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EribulinDrug
Intravenous eribulin administered on days 1 and 8 of a 21-day cycle.
IrinotecanDrug
Irinotecan will be administered orally at a fixed dose of 90 mg/m2/day on days 1 -5 of a 21-day cycle.
CefiximeOther
Also called Suprax
Cefixime will be given to all patients to reduce irinotecan-associated diarrhea. It will be administered Day -1 through Day 8 of each cycle.
| Study group | Role | What they receive |
|---|---|---|
| Eribulin + Irinotecan | Experimental | 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.
Eribulin dose will be assigned at time of enrollment using a 3+ 3 Phase 1 design (ranging from 0.8 - 1.4 mg/m2/dos). The dose of irinotecan will be fixed at 90 mg/m2/day x 5 days. Receives: Drug: Eribulin; Drug: Irinotecan; Other: Cefixime |
What is being measured
The primary outcome is the main question the study is designed to answer.
The 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. A 3+3 trial design will be utilized. Accrual will continued based on DLT evaluation until the RP2D is established and at least 6 patients have been treated at this dose.
Measured: Within 2 years
Secondary outcomes (5)
The number of patients with adverse events (according to CTCAE V.4) in patients receiving the combination of eribulin and irinotecan
The intensity of AEs will be graded according to the CTCAE V.4 on a 5-point scale
Measured: Within 2 years
The best overall response based on RECIST 1.1 criteria
To estimate the anti-tumor effects of the eribulin and irinotecan drug combination using RECIST 1.1 criteria
Measured: Within 2 years
The area under the plasma concentration versus time curve of eribulin in adolescent and young adult patients receiving oral irinotecan
Pharmacokinetic measurements will be performed on days 1 and 8 of the first cycle
Measured: 2 years
The peak plasma clearance, Cmax, of eribulin in adolescent and young adult patients receiving oral irinotecan
Pharmacokinetic measurements will be performed on Days 1 and 8 of the first cycle
Measured: 2 years
The half-life of eribulin in adolescent and young adults patients receiving oral irinotecan
Pharmacokinetic measurements will be performed on Days 1 and 8 of the first cycle
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2015 (estimated)
- Study start21 Oct 2015
- Primary completionApr 2019
- Study completion24 Jan 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsed Solid TumorsStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- University of Kentucky
- Responsible party
- Sponsor
- Investigators
- Carrye Cost, MD, Principal investigator, University of Colorado, DenverTom Badgett, MD, Principal investigator, University of Kentucky
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02596503
- Sponsor's protocol ID
- 15-0659.cc
- Status last verified
- Jan 2022
- First submitted
- 19 Oct 2015
- Last updated
- 15 Feb 2022
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study of Eribulin in Combination With Oral Irinotecan for Adolescent and Young Adult Patients With Relapsed or Refractory Solid Tumors
- ClinicalTrials.gov ID
- NCT02596503
- Acronym / sponsor ID
- 15-0659.cc
- Conditions
- Relapsed Solid Tumors, Refractory Solid Tumors
- Keywords
- young adults, adolescents
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- University of Kentucky
- Study start
- 21 Oct 2015 (actual)
- Primary completion
- Apr 2019 (actual)
- Study completion
- 24 Jan 2020 (actual)
- First posted
- 4 Nov 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This IND-exempt Phase I trial will establish the recommended Phase II (RP2D) 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, and there will be no intrapatient dose escalation. Once the RP2D has been established, there will be up to 10 patients enrolled in a dose expansion cohort. In absence of disease progression or toxicity, subjects may receive up to 17 cycles of therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Eribulin + Irinotecan | Experimental | Drug: Eribulin, Drug: Irinotecan, Other: CefiximeEribulin 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. Eribulin dose will be assigned at time of enrollment using a 3+ 3 Phase 1 design (ranging from 0.8 - 1.4 mg/m2/dos). The dose of irinotecan will be fixed at 90 mg/m2/day x 5 days. |
Who may qualify
- Ages
- 13 to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (24 listed)
- Patients must ≥13 and ≤30 years of age at the time of study entry
- 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 GIST, alveolar soft part sarcoma, or dematofibrosarcoma protuberans 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.
Key exclusion criteria (19 listed)
- 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.
- Major surgery within 14 days prior to start of treatment. No time limitations after minor surgery (eg: core biopsy or central line placement)
- Current evidence of GIST, alveolar soft part sarcoma, or dermatofibrosarcoma
- Concomitant Medications:
- Infection: Patients who have an uncontrolled infection, or who are currently receiving treatment for C difficile infection.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EribulinIntravenous eribulin administered on days 1 and 8 of a 21-day cycle. | Drug | Eribulin + Irinotecan |
| IrinotecanIrinotecan will be administered orally at a fixed dose of 90 mg/m2/day on days 1 -5 of a 21-day cycle. | Drug | Eribulin + Irinotecan |
| CefiximeAlso: SupraxCefixime will be given to all patients to reduce irinotecan-associated diarrhea. It will be administered Day -1 through Day 8 of each cycle. | Other | Eribulin + Irinotecan |
Primary outcome
The recommended Phase II dose of eribulin when used in combination with oral irinotecan
Time frame: Within 2 years
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. A 3+3 trial design will be utilized. Accrual will continued based on DLT evaluation until the RP2D is established and at least 6 patients have been treated at this dose.
5 secondary outcomes
The number of patients with adverse events (according to CTCAE V.4) in patients receiving the combination of eribulin and irinotecan
Time frame: Within 2 years
The best overall response based on RECIST 1.1 criteria
Time frame: Within 2 years
The area under the plasma concentration versus time curve of eribulin in adolescent and young adult patients receiving oral irinotecan
Time frame: 2 years
The peak plasma clearance, Cmax, of eribulin in adolescent and young adult patients receiving oral irinotecan
Time frame: 2 years
The half-life of eribulin in adolescent and young adults patients receiving oral irinotecan
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2022.
Related trials for Relapsed Solid Tumors
RecruitingPhase 1
IL-12 Genetically Engineered Myeloid Cells in Participants With Relapsed, Refractory Solid Tumors
Relapsed Solid Tumor Malignancies, Refractory Solid Tumor Malignancies
RecruitingPhase 1/2
Study of Lurbinectedin Monotherapy in Pediatric and Young Adult Participants With Relapsed/Refractory Ewing Sarcoma
Refractory Ewing Sarcoma, Relapsed Ewing Sarcoma
Active, not recruitingPhase 1/2
Safety and Dose Finding Study of Neratinib in Children and Young Adults With Cancer That Has Returned or Not Responded to Treatment
Solid Tumor, Central Nervous System Tumor
Active, not recruitingPhase 1/2
VITAS: Atezolizumab in Combination With Chemotherapy for Pediatric Relapsed/Refractory Solid Tumors
Solid Tumor, Rhabdomyosarcoma
Not yet recruitingPhase 1
GD2IL18CART Combined With Bevacizumab for Relapsed and Refractory GD2-positive Solid Tumors
Neuroblastoma (NBL), Ewing Sarcoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Carrye Cost, MD principal investigator
University of Colorado, Denver
Tom Badgett, MD principal investigator
University of Kentucky
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Eribulin, Irinotecan and Cefixime in people with Relapsed Solid Tumors and Refractory Solid Tumors, run by University of Colorado, Denver at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The recommended Phase II dose of eribulin when used in combination with oral irinotecan (time frame: Within 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Feb 2022.