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

NCT02116959 | Terminated Phase 1 DMC FDA Drug

• 2 other identifiers: 13087NCI-2015-01749
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Advanced Intra-Ocular Retinoblastoma; Retinoblastoma

Keywords

Systemic; Chemotherapy; Melphalan

Outcome Measures

Primary Outcomes (2)

• Adverse Event evaluation for newly diagnosed advanced retinoblastoma treated with melphalan therapy and systemic chemotherapy

  Up to 2 years

• Dose-Limiting Toxicity (DLT) and minimum tolerated dosing interval for combination IAM and carboplatin, vincristine, and etoposide (CEV).

  Up to 2 years

Secondary Outcomes (6)

• Response rates after IAM combined with systemic CEV in patients with newly diagnosed advanced intraocular retinoblastoma

  Up to 2 years

• Ocular event free survival with the use of combination IAM therapy and systemic CEV in this patient population.

  Up to 2 years

• Visual outcomes using a standardized age based assessment

  Up to 2 years

• Salvage rate with triple IA therapy after failure of IA melphalan

  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.

  Up to 2 years

Other Outcomes (1)

• Collection of melphalan pharmacokinetics after intra-arterial administration to the retina

  Up to 2 years

Study Arms (2)

Cohort 1

EXPERIMENTAL

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

Cohort 2

EXPERIMENTAL

Patients will receive only intra-arterial (IA) therapy for more limited disease.

Drug: Melphalan; Drug: Carboplatin; Drug: Etoposide; Drug: Vincristine

Interventions

Melphalan DRUG

Cohort 1; Cohort 2

Carboplatin DRUG

Cohort 1; Cohort 2

Etoposide DRUG

Cohort 1; Cohort 2

Vincristine DRUG

Cohort 1; Cohort 2

Eligibility Criteria

• Age: 3 Months - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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 retinoblastoma (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):
• Group A eye that has failed local therapy
• Group B eye that has failed local therapy
• Group C eye that has failed local therapy
• Group D eye
• Group E eye that is not buphthalmic, 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):
• Group A and Group A eyes that have failed local therapy
• Group A and Group B eyes that have failed local therapy

You may not qualify if:

• Any evidence of extraocular retinoblastoma clinically or by magnetic resonance imaging (MRI) of brain and orbits with and without gadolinium. MRI may be done within 21 days prior to study entry.
• \. Evidence of systemic metastases on bilateral bone marrow, lumbar puncture, bone scan (or Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) scan), and/or any other additional tests done at study entry.
• 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.

Sponsors & Collaborators

• University of California, San Francisco: lead

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

MeSH Terms

Conditions

Retinoblastoma

Interventions

Melphalan; Carboplatin; Etoposide; Vincristine

Condition Hierarchy (Ancestors)

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, Hereditary; Eye Diseases; Retinal Diseases

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Coordination Complexes; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Officials

• Anuradha Banerjee, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 18, 2014
• First Posted: April 17, 2014
• Study Start: July 23, 2014
• Primary Completion: May 25, 2019
• Study Completion: May 25, 2019
• Last Updated: April 16, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)