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Pediatric Solid TumorsPhase 2NCT02747537

Treating Relapsed/Recurrent/Refractory Pediatric Solid Tumors With Sorafenib in Combination With Irinotecan

A Phase 2 study testing Sorafenib and Irinotecan in people with Pediatric Solid Tumors, run by Washington University School of Medicine.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This study proposes to treat patients with the combination of sorafenib and irinotecan. Patients with relapsed, recurrent, refractory, or high risk malignancies whose tumors possess a non-synonymous mutation in Raf, PDGFR, VEGFR, Flt-3, KIT, JAK, STAT, RAS, MEK, or ERK will be eligible for the study. Read more about this study

Who is it for?
Ages 24 months to 21 years
Conditions the study is for
Pediatric Solid Tumors
What is being tested?
Sorafenib and Irinotecan
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
24 Jun 2016to 29 Feb 2020
Phase
Phase 2
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 24 months to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Greater than or equal to 24 months to 21 years of age
  • Relapsed, refractory, or recurrent malignancy. All solid tumor diagnoses will be eligible.
  • Pathologic confirmation of the diagnosis either at original diagnosis or recurrence.
  • Known non-synonymous mutation in the following genes: Raf, PDGFR, VEGFR, Flt-3, KIT, JAK, STAT, RAS, MEK, or ERK. Genomic sample preferably from relapse, but may be from other stage of treatment if relapse sample is not reasonably obtainable. Genetic analysis for determination of eligibility occurs as part of routine care and is not being performed specifically for the purposes of this study.
  • Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT or MRI scan, as ≥ 20 mm by chest x-ray, or ≥ 10 mm with calipers by clinical exam.
  • Prior Therapy
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  • Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
  • Myelosuppressive chemotherapy: Patients must not have received myelosuppressive chemotherapy within 2 weeks of enrollment onto this study (6 weeks if prior nitrosourea).
  • Hematopoietic growth factors: At least 14 days must have elapsed after receiving pegfilgrastim and least 7 days must have elapsed since the completion of therapy with a non-pegylated growth factor.
  • Biologic (anti-neoplastic agent): At least 7 days must have elapsed since completion of therapy with a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period prior to enrollment must be extended beyond the time during which adverse events are known to occur.
  • Monoclonal antibodies: At least 3 half-lives must have elapsed since prior therapy that included a monoclonal antibody. (See posting of half-lives for commonly used monoclonal antibodies on the DVL homepage; https://members.childrensoncologygroup.org/Disc/devtherapeutics/default.asp.)
  • Radiotherapy: ≥ 2 weeks must have elapsed since local palliative XRT (small port); ≥ 6 weeks must have elapsed since treatment with therapeutic doses of MIBG; ≥ 3 months must have elapsed if prior craniospinal XRT was received, if ≥ 50% of the pelvis was irradiated, or if TBI was received; ≥ 6 weeks must have elapsed if other substantial bone marrow irradiation was given.
  • Stem Cell Transplant or Rescue without TBI: No evidence of active graft vs. host disease and ≥ 2 months must have elapsed since transplant.
  • Patients must have a performance status corresponding to Karnofsky or Lansky greater than or equal to 50%. Use Karnofsky for patients > 16 years of age and Lansky for patients ≤ 16 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
  • Normal bone marrow and organ function as defined below:
  • Absolute neutrophil count ≥ 1,000/mcl
  • Platelets ≥ 75,000/mcl (transfusion independent, defined as not receiving platelet transfusions within a 7 day period prior to enrollment)
  • Total bilirubin ≤ IULN
  • AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN Note: For the purposes of this trial the ULN for ALT is defined as 45 U/L.
  • Adequate Renal Function Defined As: Creatinine clearance or radioisotope GFR > 70 mL/min/1.73 m2 or a serum creatinine based on age/gender as follows: 2 to < 6 years (male=0.8, female=0.8), 6 to <10 years (male=1, female=1), 10 to < 13 years (male=1.2, female=1.2), 13 to < 16 years (male=1.5, female=1.4), and ≥ 16 years (male=1.7, female=1.4)
  • PTT < IULN
  • INR < IULN or PT < IULN
  • Normal serum lipase and amylase (per institutional normal values).
  • Adequate Pulmonary Function Defined As: No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry > 94%.
  • Adequate cardiovascular functioning for sorafenib, including:
  • Shortening fraction ≥ 28% or ejection fraction (LVEF) ≥ 55%, as well as
  • A blood pressure (BP) ≤ the 95th percentile for age, height, and gender and not receiving medication for treatment of hypertension.
  • Normal electrocardiogram with QTc < 450.
  • Women of childbearing potential and men 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. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
  • Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

Who cannot join

  • Patients who have received a cumulative doxorubicin equivalent of > 375mg/m^2 total lifetime dose.
  • Surgery Criteria: Patients who have had or are planning to have the following invasive procedures are not eligible:
  • Major surgical procedure, laparoscopic procedure, open biopsy or significant traumatic injury within 14 days prior to initiation of protocol therapy. There should be no anticipation of need for major surgical procedures during the course of the study.
  • Central line placement or subcutaneous port placement is not considered major surgery. External central lines must be placed at least 3 days prior to initiation of protocol therapy and subcutaneous ports must be placed at least 7 prior to initiation of protocol therapy
  • Patients must not be on therapeutic anti-coagulation. Prophylactic anticoagulation (i.e. low dose warfarin) of venous or arterial devices is allowed provided that the requirements for PT, INR, and PTT are met.
  • Patients with evidence of bleeding diathesis are not eligible.
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  • Patients with known Gilbert syndrome are not eligible.
  • A history of other malignancy ≤ 5 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix.
  • Currently receiving any other investigational agents.
  • A history of allergic reactions attributed to compounds of similar chemical or biologic composition to sorafenib or irinotecan.
  • Currently on the following concomitant medications or substances that have the potential to affect the activity or pharmacokinetics of the study drug(s). The use of the following medications should be discontinued prior to initiation of protocol therapy and should be avoided during protocol therapy if reasonable alternatives exist.
  • Sorafenib
  • Irinotecan
  • Corticosteroids: Patients requiring corticosteroids that have not been on a stable or decreasing dose of corticosteroid for 7 days prior to enrollment are not eligible.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, cardiac dysfunction, unstable angina pectoris, cardiac arrhythmia, prolonged QTc, interstitial lung disease, gastrointestinal perforation, hepatic impairment/failure, or renal impairment/failure.
  • Pregnant and/or breastfeeding. Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days of study entry.
  • Known HIV-positivity on combination antiretroviral therapy because of the potential for pharmacokinetic interactions with sorafenib or irinotecan. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.

About this study

Official title: Phase 2 Clinical Trial Treating Relapsed/Recurrent/Refractory Pediatric Solid Tumors With the Genomically-Targeted Agent Sorafenib in Combination With Irinotecan

This study proposes to treat patients with the combination of sorafenib and irinotecan. Patients with relapsed, recurrent, refractory, or high risk malignancies whose tumors possess a non-synonymous mutation in Raf, PDGFR, VEGFR, Flt-3, KIT, JAK, STAT, RAS, MEK, or ERK will be eligible for the study. Very few phase 2 clinical trials have been performed in pediatrics using targeted agents in combination with conventional chemotherapy agents. Furthermore, since some combinations such as the combination of this study (sorafenib and irinotecan) have shown additive/synergistic effects in preclinical studies, therapy selecting for those patients who possess mutations targeted by the TKI of the study, may unveil activity that has not been previously observed. Thus, the investigators hope to determine whether the addition of additive/synergistic chemotherapy will increase efficacy of the targeted agent and/or increase tumor susceptibility to the targeted agent, resulting in increased anti-tumor activity.

Being tested
Sorafenib, Irinotecan

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02747537
Study groupRoleWhat they receive
Arm 1: Sorafenib and IrinotecanExperimental* Sorafenib is an oral drug which will be administered on an outpatient basis twice a day continuously (every day of a 21-day cycle) at approximately the same times each day. For patients unable to swallow whole pills, an oral suspension may be prepared with tablets. * Irinotecan will be administered orally (mixed with "cranberry" type juice) on an outpatient basis once a day on Days 1-5 of a 21-day cycle. Irinotecan should be given at least 1 hour after sorafenib.
Receives: Drug: Sorafenib; Drug: Irinotecan

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall response rate

    • The percentage of patients who have complete response (CR) and partial response (PR)
    • CR: Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10mm. Disappearance of all target lesions and normalization of tumor marker levels.

    PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters

    Measured: Completion of treatment (18 weeks)

Secondary outcomes (2)

  1. Time to progression (TTP)

    -Progressive disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).

    Measured: Completion of treatment (18 weeks)

  2. Toxicity as measured by grade, frequency, and relatedness of adverse events per CTCAE version 4.0

    Measured: 30 days after the completion of treatment (22 weeks)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Apr 2016 (estimated)
  2. Study start24 Jun 2016
  3. Primary completion31 Jan 2020 (estimated)
  4. Study completion29 Feb 2020 (estimated)

Why it stopped: Could not recruit participants for the study

Resources

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02747537
Sponsor's protocol ID
201605006
Status last verified
Sep 2019
First submitted
19 Apr 2016
Last updated
9 Sep 2019
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Sorafenib and Irinotecan in people with Pediatric Solid Tumors, run by Washington University School of Medicine.

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 30 inclusion and 17 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: withdrawn, as of the sponsor's last update on 9 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.

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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 was withdrawn before enrolling participants, so there are no results.

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?

Overall response rate (time frame: Completion of treatment (18 weeks)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02747537.

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 9 Sep 2019.

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