Prospective Pilot Trial to Assess a Multimodal Molecular Targeted Therapy in Children, Adolescent and Young Adults With Relapsed or Refractory High-grade Pineoblastoma

NCT02596828 | Completed Phase 2

• 1 other identifier: RIST-rPB-2015-P
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

Children, adolescents and young adults with relapsed or treatment refractory pineoblastoma (rPB) represent a group of patients with dismal prognosis for whom a recommended standard salvage therapy is currently not available.

Conditions

Pineoblastoma

Keywords

molecular targeted therapy; protein kinase inhibitor; mTOR Inhibitor; cytostatic topoisomerase-I-inhibitor; temozolomide; irinotecan; dasatinib; rapamycin

Outcome Measures

Primary Outcomes (1)

• The primary endpoint is progression-free survival (PFS)

  According to: * Imaging criteria to * MRI, CT or * CSF evaluations or * date of death of any cause

  Time interval from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 52 weeks

Secondary Outcomes (6)

• Overall survival (OS)

  From the first course of the investigational treatment up to the end of the trial assessed to 52 weeks

• Response to the investigational treatment after 4 and 8 courses of I/T and 1-year-follow-up in the RIST treatment arm

  From the first course of the investigational treatment up to the end of the trial assessed to 52 weeks

• Duration until adequate response to this treatment regimen

  From the first course of the investigational treatment up to the end of the trial assessed to 52 weeks

• Assessment of quality of life (Lansky and Karnofsky Scores)

  From the first course of the investigational treatment up to the end of the trial assessed to 52 weeks

• Toxicity of this combination of drugs in children, adolescents and young adults with rNB - Assessment according to the latest version of the CTC criteria

  From the first course of the investigational treatment up to the end of the trial assessed to 52 weeks

Study Arms (1)

RIST

EXPERIMENTAL

Drug: Temozolomide; Drug: Irinotecan; Drug: Dasatinib; Drug: Rapamycin

Interventions

Temozolomide DRUG

Pharmacotherapeutic Group: Antineoplastic agents - Other alkylating agents, ATC-Code: L01A X03 Excipients: Capsule content: Anhydrous lactose, Sodium starch glycolate Type A, Colloida anhydrous silica, Tartaric acid, Stearic acid. Capsule shell: Gelatine, Titanium dioxide (E171). Printing ink: Shellac Propylene glycol, Titanium dioxide (E171), Sunset yellow FCF Aluminium Lake (E110) Formulation: capsule, hard Route of Administration: orally; Temomedac hard capsules should be administered in the fasting state. The capsules must be swallowed whole with a glass of water and must not be opened or chewed

Also known as: Temomedac

RIST

Irinotecan DRUG

Pharmacotherapeutic Group: cytostatic topoisomerase-I-inhibitor ATC-Code: L01XX19 Excipients: Sorbitol (E420), lactic acid, sodium hydroxid (to adjust the pH to 3.5), water for injection Formulation: concentrate for solution for infusion Route of Administration: intravenously

Also known as: Irinomedac

RIST

Dasatinib DRUG

Pharmacotherapeutic Group: protein kinase inhibitor ATC-Code: L01XE06 Excipients: Tablet core: Lactose monohydrate, Cellulose, microcrystalline, Croscarmellose sodium, Hydroxypropyl cellulose, Magnesium stearate. Film-coating: Hypromellose, Titanium dioxide, Macrogol 400 Formulation: film coated tablet Route of Administration: orally. Patients should be instructed to swallow the tablets as a whole and not to split, chew, or crush them.

Also known as: Sprycel

RIST

Rapamycin DRUG

Pharmacotherapeutic Group: Immunosuppressive agents - mTOR Inhibitors ATC-Code: L04A A10 Excipients: Polysorbat 80, Phosal 50 PG ((3-sn-Phosphatidyl)cholin from Soy beans, Propylenglycol, lipid acid mono- and -diglyzeride from Soy oil, Ethanol (1,5% bis 2,5%), Soy liid acid and Palmitoyl ascorbic acid) Formulation: Oral solution Route of Administration:orally

Also known as: Rapamune

RIST

Eligibility Criteria

• Age: 0 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients with relapsed and refractory high-grade pineoblastome (=rPB) and all of the following criteria will be considered for admission to the clinical trial:
• Children, adolescents and young adults 0 months to 25 years
• Signed written informed consent (patient or his/her parents/legal guardian)
• Females of childbearing age must have a negative urine pregnancy test prior to starting the study drug. The first pregnancy test must be performed within 10-14 days prior to the start of the study drug and the second pregnancy test must be performed within 24 hours prior to the start of study drug. The subject may not receive the study drug until the investigator has verified that the results of these pregnancy tests are negative.
• Females of childbearing age must comply with the institutional standards of birth control with a pearl index \<1%. Contraception must be started at least four weeks before the start of the investigational therapy.
• Females of childbearing age must be willing to abstain from breastfeeding for the duration of the clinical trial and for at least 30 days after discontinuation of the clinical trial.
• Males must agree not to father a child and must use latex condom during any sexual contact with women of childbearing age during and for 6 months after therapy ends or is stopped, even if they have undergone successful vasectomy.
• Willing and able to complete the clinical trial procedures, as described in the protocol
• Non-smoker for at least the previous 3 months. Smoking is not allowed during the entire study period
• Abstain from alcohol within the last 24 hours before screening and before admission to the clinical trial center as well as during the entire clinical trial. The regular daily ethanol intake has to be less than 20g/day for at least the previous three months.
• Patients are required to have an absolute neutrophil count (ANC) ≥500/µL, hemoglobin ≥8g/dL (transfusion permitted), and an unsupported platelet count ≥30,000/µL unless:
• patient is refractory or relapsed early after primary therapy

You may not qualify if:

• Patients presenting with any of the following criteria will not be included in this clinical trial:
• Pregnancy, nursing
• Patients who suffered from a thrombotic event and need anticoagulation (i.e. coumadine derivatives or low molecular weight heparin derivatives, LMWH)
• Patients with cardiac arrhythmias especially prolonged QT
• Patients with chronic inflammatory bowel diseases and/or bowel obstruction
• Patients with bilirubin serum levels 1,5 fold above the upper normal limit
• Vaccination with a live virus vaccine during the clinical trial
• Impaired liver function and/or impaired renal function (hepatic and renal index parameter two times above normal range; see below)
• Potentially unreliable subjects, probably non compliant subjects and those judged by the investigator to be unsuitable for the study
• Doubts about the patient's cooperation
• Any contraindications or known hypersensitivity to the IMPs or to any of the other components: (see SPC "Fachinformation")
• Known allergic reactions to the treatment medication
• Patients who were treated with radiation and/or chemotherapy for any other oncological condition
• Participation in any other interventional phase I to III trial
• Sexually active patients who refuse to use contraception according to the institutional requirements

Sponsors & Collaborators

• University of Regensburg: lead

Study Sites (1)

University Hospital of Regensburg

Regensburg, 93053, Germany

Location

MeSH Terms

Conditions

Pinealoma

Interventions

Temozolomide; Irinotecan; Dasatinib; Sirolimus

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Camptothecin; Alkaloids; Thiazoles; Sulfur Compounds; Pyrimidines; Macrolides; Lactones

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Dr. med.

Study Record Dates

• First Submitted: October 28, 2015
• First Posted: November 4, 2015
• Study Start: April 1, 2016
• Primary Completion: April 1, 2021
• Study Completion: April 1, 2021
• Last Updated: August 5, 2021

Record last verified: 2021-07

Locations

DE (1)