Episcleral Topotecan for Treatment of Group D Retinoblastoma

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Brief Title

Topotecan Episcleral Plaque for Treatment of Retinoblastoma

Official Title

A Phase I Study of Sequestered Transscleral, Controlled-Release Topotecan Delivered From an Episcleral Reservoir in Retinoblastoma Eyes

Brief Summary

      This single-arm, non-randomized, dose escalation phase I clinical trial will assess primarily
      the safety and secondarily the efficacy of episcleral topotecan in patients with active de
      novo or recurrent intraocular retinoblastoma in at least one eye following completion of
      first-line therapy.
    

Detailed Description

      Retinoblastoma is the most common pediatric malignant intraocular tumor and originates from
      the retina. Treatment of eyes with advanced intraocular retinoblastoma remains a challenge.
      The historic standard of care for patients with unilateral disease is enucleation and for
      those with bilateral disease, a variety of modalities have been tried. These include
      radiation therapy, systemic chemotherapy, periocular administration of chemotherapy,
      selective intra-arterial chemotherapy, and intravitreal chemotherapy. Unfortunately, all of
      these modalities are associated with significant morbidity and investigators are looking for
      new ways to treat these patients either with novel directed drug delivery methods or with new
      less toxic agents. This study will evaluate the safety and efficacy of topotecan delivered
      directly to the eye using a novel sustained-release topotecan episcleral delivery system
      (also referred to as a Chemoplaque) in patients with active de novo or recurrent intraocular
      retinoblastoma in at least one eye following completion of first-line therapy. The study
      intervention involves the insertion and removal of the Chemoplaque, examinations under
      anaesthesia (EUAs), visits to clinic to monitor for adverse events throughout, and post
      plaque removal toxicity evaluation. EUAs, clinic visits and laboratory tests are standard of
      care for retinoblastoma patients.
    

Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

To determine the safety and tolerability of Episcleral Topotecan in participants with retinoblastoma-Maximum Tolerated Dose (MTD) and/or Recommended Phase II Dose (RP2D).

Secondary Outcome

 To determine systemic exposure by measurement of Topotecan in plasma.

Condition

Retinoblastoma

Intervention

Episcleral Topotecan

Study Arms / Comparison Groups

 Phase I Open Label Study
Description:  Phase I Single Arm

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

30

Start Date

June 16, 2021

Completion Date

October 14, 2023

Primary Completion Date

October 1, 2023

Eligibility Criteria

        Inclusion Criteria:

        Age: Participants must be < 18 years of age.

        Diagnosis and Treatment. Participants must have:

        Unilateral Group D or earlier-stage intraocular retinoblastoma in which enucleation is a
        recommended therapy, with no previous local or systemic therapy for retinoblastoma with
        intraocular calcium in the tumor-containing eye by ophthalmic ultrasound or neuroimaging.

        OR Active residual or recurrent intraocular retinoblastoma in at least one eye following
        completion of first-line therapy (focal therapy for IIRC Group A eyes, or systemic or
        intra-arterial chemotherapy).

        One eye will be the Study Eye. When participants have two eyes with retinoblastoma, the eye
        with worst disease or best vision potential will be designated the Study Eye. There will
        only be one eye per child treated in this Phase I study, since treatment of two eyes would
        double the systemic dose of drug. The Non-study eye will be treated by standard of care,
        with only focal therapy during the Study Period, if required.

        Must have demonstrated intraocular calcium in the tumor-containing eye by ophthalmic
        ultrasound or by neuroimaging as part of standard retinoblastoma diagnosis.

        Study eye must have vision potential, at least light perception vision in the tumor-bearing
        eye either with pupil response testing or demonstration of avoidance behavior to light
        presentation in the affected eye, and no clinical features suggestive of high risk of
        extraocular extension.

        Performance Level: Lansky greater than or equal 50 (<16 years of age); Karnofsky
        performance scale of >50 (>16 years of age).

        Organ Function Requirements:

          1. Adequate Bone Marrow Function defined as:

               -  Peripheral absolute neutrophil count (ANC) greater than or equal 1000/mm3

               -  Platelet count greater than or equal 100,000/mm3 (transfusion independent,
                  defined as not receiving platelet transfusions for at least 7 Days prior to
                  enrollment)

               -  Hemoglobin greater than or equal 8.0 g/dL at baseline (may receive RBC
                  transfusions)

          2. Adequate Renal Function defined as:

               -  Creatinine clearance or radioisotope GFR greater than or equal 70ml/min/1.73 m2
                  or

               -  A serum creatinine based on age/gender as follows:

             Age Maximum Serum Creatinine (mg/dL) Male Female

             1 month to < 6 months 0.4 0.4 6 months to < 1 year 0.5 0.5

               1. to < 2 years 0.6 0.6

               2. to < 6 years 0.8 0.8

             6 to < 7 years 1 1

             The threshold creatinine values in this Table were derived from the Schwartz formula
             for estimating GFR utilizing child length and stature data published by the CDC.

          3. Adequate Liver Function defined as:

               -  Bilirubin (sum of conjugated + unconjugated) less than or equal 1.5 x upper limit
                  of normal (ULN) for age.

               -  SGPT (ALT) less than or equal 110 U/L. For the purpose of this study, the ULN for
                  SGPT is 45 U/L.

               -  Serum albumin greater than or requal 2 g/dL.

          4. Pregnancy prevention. Females of reproductive potential must agree to the use of
             highly effective contraception during study participation and for an additional 40
             days after the end of Episcleral Topotecan administration.

          5. Informed consent. All participants and/or their parents or legally authorized
             representatives must have the ability to understand and the willingness to sign a
             written informed consent. Assent, where appropriate, will also be obtained.

        Exclusion Criteria

        Disease status. Participants known to have any of the following are excluded:

          1. tumor involving the optic nerve rim

          2. clinical or EUA evidence of extraocular extension

          3. evidence of metastatic retinoblastoma

          4. existing neuroimaging showing suspicion of, or definitive, optic nerve . invasion,
             trilateral retinoblastoma or extra-ocular extension.

        Allergy. Participants with reported allergy to topotecan, camptothecin or derivatives
        thereof are excluded.

        Concomitant treatment. Participants who have received chemotherapy, other focal
        retinoblastoma therapy or any other investigational agent within 3 weeks of Episcleral
        Topotecan placement are not eligible.

        Uncontrolled intercurrent illness. Participants with known uncontrolled intercurrent
        illness that, in the investigator's opinion, would put the participant at undue risk or
        limit compliance with the study requirements, are not eligible.

        Febrile illness. Participants with clinically significant febrile illness (as determined by
        the investigator) within one week prior to initiation of protocol therapy are excluded.

        Pregnancy and lactation. Females of reproductive potential must have a negative serum
        pregnancy test within 72 hours prior to initiation of protocol therapy. Due to the unknown
        but potential risk for adverse events (AEs) in nursing infants secondary to treatment of
        the mother with the study agents, breastfeeding must be discontinued if the mother is
        treated on study.

        Compliance. Any condition of diagnosis that could in the opinion of the Principal
        Investigator or delegate interfere with the participant's ability to comply with the study
        instruction, might confound the interpretation of the study results, or put the participant
        at risk.
      

Gender

All

Ages

N/A - 18 Years

Accepts Healthy Volunteers

No

Contacts

, 949-892-5363, [email protected]

Location Countries

Canada

Location Countries

Canada

Administrative Informations


NCT ID

NCT04156347

Organization ID

3TRB01


Responsible Party

Sponsor

Study Sponsor

Targeted Therapy Technologies, LLC


Study Sponsor

, , 


Verification Date

September 2021