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Alternating Systemic Chemotherapy and Intra-Arterial Melphalan Chemotherapy in Children With Intra-Ocular Retinoblastoma

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02116959
First Posted: April 17, 2014
Last Update Posted: November 29, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Anuradha Banerjee, University of California, San Francisco
  Purpose
The purpose of this study is to test the safety of the treatment combination of alternating standard chemotherapy and another (melphalan) chemotherapy at different interval schedules. Researchers want to find out what effects, good and/or bad, the treatment combination has on the patients and their retinoblastoma.

Condition Intervention
Advanced Intra-Ocular Retinoblastoma Retinoblastoma Drug: Melphalan Drug: Carboplatin Drug: Etoposide Drug: Vincristine

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Study Evaluating the Safety of Alternating Systemic Chemotherapy and Intra-Arterial Melphalan Chemotherapy in Children With Newly Diagnosed Advanced Intra-Ocular Retinoblastoma

Resource links provided by NLM:


Further study details as provided by Anuradha Banerjee, University of California, San Francisco:

Primary Outcome Measures:
  • Adverse Event evaluation for newly diagnosed advanced retinoblastoma treated with melphalan therapy and systemic chemotherapy [ Time Frame: Up to 2 years ]
  • Dose-Limiting Toxicity (DLT) and minimum tolerated dosing interval for combination IAM and CEV. [ Time Frame: Up to 2 years ]

Secondary Outcome Measures:
  • Response rates after IAM combined with systemic CEV in patients with newly diagnosed advanced intraocular retinoblastoma [ Time Frame: Up to 2 years ]
  • Ocular event free survival with the use of combination IAM therapy and systemic CEV in this patient population. [ Time Frame: Up to 2 years ]
  • Visual outcomes using a standardized age based assessment [ Time Frame: Up to 2 years ]
  • Salvage rate with triple IA therapy after failure of IA melphalan [ Time Frame: Up to 2 years ]
  • Ocular event free survival for unilateral retinoblastoma with IA chemotherapy only for Group C or Group A/B that failed local therapy. [ Time Frame: Up to 2 years ]
  • Visual outcomes using a standardized age based assessment. [ Time Frame: Up to 2 years ]

Other Outcome Measures:
  • Collection of melphalan pharmacokinetics after intra-arterial administration to the retina [ Time Frame: Up to 2 years ]

Enrollment: 6
Study Start Date: April 2014
Estimated Study Completion Date: May 2019
Primary Completion Date: May 25, 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1

Patients will receive alternating treatments beginning with systemic chemotherapy then followed by IA (intra-arterial) therapy.

Bilateral retinoblastoma patients will be in Cohort 1.

For bilateral Bilateral retinoblastoma patients where one eye is stage A or B and the other eye is C, D, or E, only the higher stage eye (C, D, E) will be treated with IA chemotherapy unless the stage A or B eye is not amenable or has failed local therapy.

Drug: Melphalan Drug: Carboplatin Drug: Etoposide Drug: Vincristine
Experimental: Cohort 2
Patients will receive only IA (intra-arterial) therapy for more limited disease.
Drug: Melphalan Drug: Carboplatin Drug: Etoposide Drug: Vincristine

  Eligibility

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Ages Eligible for Study:   3 Months to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age greater than or equal to 3 months up to 18 years.
  • Intraocular retinoblastoma not previously treated with systemic chemotherapy, radiation therapy, or IA therapy. Local retinal therapy such as laser photocoagulation and cryotherapy will be permitted.
  • Unilateral or bilateral RB patients are eligible
  • Patients will be registered on study based on the local exam under anesthesia (EUA) done for diagnostic purposes prior to study entry. The EUA done at study entry should be done within 14 days prior to study entry
  • Patients may have had enucleation of one eye, as long as the remaining eye meets the eligibility criteria
  • Involved eye(s) must meet the definition for International Classification of Retinoblastoma
  • For unilateral retinoblastoma (see Appendix 1 for International Classification of Retinoblastoma):

    1. Group A eye that has failed local therapy
    2. Group B eye that has failed local therapy
    3. Group C eye that has failed local therapy
    4. Group D eye
    5. Group E eye that is not bupthalmic, is not planned for enucleation after first cycle of chemotherapy, and is in a child less than 1 year of age
  • For bilateral retinoblastoma (see Appendix 1 for International Classification of Retinoblastoma):

    1. Group A and Group A eyes that have failed local therapy
    2. Group A and Group B eyes that have failed local therapy
    3. Group A and Group C eyes
    4. Group A and Group D eyes
    5. Group A and Group E eyes in which the Group E eye is not planned for enucleation after first cycle of chemotherapy
    6. Group B and Group B eyes that have failed local therapy
    7. Group B and Group C eyes
    8. Group B and Group D eyes
    9. Group B and Group E eyes in which the Group E eye is not planned for enucleation after first cycle of chemotherapy
    10. Group C and Group C eyes
    11. Group C and Group D eyes
    12. Group C and Group E eyes even if early enucleation is planned for the Group E eye.
    13. Group D and Group D eyes
    14. Group D and Group E eyes even if early enucleation is planned for the Group E eye.
    15. Group E and Group E eyes if at least one eye is not planned for enucleation.
  • Adequate Renal Function defined as: creatinine clearance or radioisotope GFR ³ 70mL/min/1.73 m2 OR a serum creatinine based on age and gender derived from the Schwartz formula for estimating GFR (Schwartz et al. J. Peds, 106:522, 1985) utilizing child length and stature data published by the CDC.
  • Adequate hematological function defined as:

    1. Absolute Neutrophil Count > 1000/microliter
    2. Platelet Count > 100,000/microliter
  • Adequate liver function defined as total bilirubin should be less than or equal to 1.5 x upper limit of normal (ULN) for age and SGOT (AST) and SGPT (ALT) < 5 x upper limit of normal (ULN) for age
  • Adequate coagulation system as defined as an international normalized ratio (INR) of less than 1.4 and a partial thromboplastin time (PTT) of less than 34
  • Women and men of child-bearing potential must agree to use adequate contraception such as hormonal or barrier method of birth control or abstinence prior to study entry and for the duration of study participation. Should the subject or the subject's partner become pregnant or suspect pregnancy while on protocol therapy, the treating physician must be informed immediately.

Exclusion Criteria:

  • Any evidence of extraocular retinoblastoma clinically or by MRI of brain and orbits with and without gadolinium. MRI may be done within 21 days prior to study entry.

    1. Evidence of systemic metastases on bilateral bone marrow, lumbar puncture, bone scan (or FDG PET scan), and/or any other additional tests done at study entry.

  • Patients who have previously been treated with chemotherapy (with the exception of second inclusion criteria) radiation therapy, or intra-arterial therapy.
  • Eyes with tumors that are amenable to local therapy with laser or cryotherapy without threat to vision
  • Any technical factor that would prohibit use of catheterization of the ophthalmic artery (e.g., small for age infant, untreatable allergy to contrast).
  • Abnormal cerebral vasculature noted on MR angiography that would increase the risk of the procedure, including but not limited to an incomplete Circle of Willis. Other abnormalities that are less severe than an incomplete Circle of Willis will be reviewed by the study chair in consultation with a neuro-interventional radiologist.
  • Any serious ongoing condition, such as an untreated infection or organ dysfunction.
  • Patients receiving any medications or substances that are inhibitors or inducers of CYP450 enzyme(s) are ineligible.
  • Pregnant women are excluded from this study due to potential for teratogenic or abortifacient effects of therapy. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother breastfeeding should be discontinued upon start of protocol therapy.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02116959


Locations
United States, California
University of California, San Francisco
San Francisco, California, United States, 94143
Sponsors and Collaborators
University of California, San Francisco
Investigators
Principal Investigator: Anuradha Banerjee, MD University of California, San Francisco
  More Information

Responsible Party: Anuradha Banerjee, Associate Clinical Professor of Pediatrics and Neurological Surgery, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT02116959     History of Changes
Other Study ID Numbers: 13087
First Submitted: February 18, 2014
First Posted: April 17, 2014
Last Update Posted: November 29, 2017
Last Verified: November 2017

Keywords provided by Anuradha Banerjee, University of California, San Francisco:
Systemic
Chemotherapy
Melphalan

Additional relevant MeSH terms:
Retinoblastoma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Retinal Neoplasms
Eye Neoplasms
Neoplasms by Site
Eye Diseases
Retinal Diseases
Carboplatin
Etoposide
Vincristine
Melphalan
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists
Immunosuppressive Agents