Prospective Pilot Trial to Assess a Multimodal Molecular Targeted Therapy in Children, Adolescent and Young Adults With Relapsed or Refractory High-grade Pineoblastoma
Condition: Pineoblastoma
MeSH terms: Pinealoma
Study type: Interventional
Phase: Phase 2

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.
    

Detailed description: 
      The multimodal metronomic approach combining molecular targeted drugs (rapamycin and
      dasatinib) with conventional chemotherapy (irinotecan and temozolomide) will be investigated
      in a randomized fashion as new treatment strategy for patients with rPB. The intention is to
      assess the therapeutic benefit of molecular targeted drugs for the treatment of rPB.

      The combination of irinotecan and temozolomide showed activity in the treatment of several
      solid organ tumors, brain tumors and neuroblastoma. In one study relapsed neuroblastoma (rNB)
      patients received a median of 5 courses of 5 days irinotecan and temozolomide every 3 to 4
      weeks with a cumulative dose of 35% lower than in the RIST design. 33% had disease regression
      with 8% CR or PR. A phase II study in rNB also using irinotecan and temozolomide with a
      substantially lower intensity showed a response rate of 15%.

      The combination of a mTOR inhibitor with a multi-kinase inhibitor demonstrated in preclinical
      studies a synergistic effect on cell cycle arrest, apoptosis and sensitization for radio- and
      chemotherapy. It is assumed that this combination of molecular targeted drugs with a
      tolerable conventional chemotherapy consisting of irinotecan and temozolomide can
      substantially improve the outcome of this patient population. A group of 20 rNB patients
      treated with the RIST therapy approach in a compassionate use setting showed an overall
      survival of 55% at a median of 80 weeks with a tolerable adverse event profile.
    

Intervention name(s): Temozolomide; Irinotecan; Dasatinib; Rapamycin
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): 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; 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; 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.; 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
Other intervention name(s): Temomedac; Irinomedac; Sprycel; Rapamune
Intervention MeSH terms: Sirolimus; Irinotecan; Temozolomide; Dasatinib
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: molecular targeted therapy; protein kinase inhibitor; mTOR Inhibitor; cytostatic topoisomerase-I-inhibitor; temozolomide; irinotecan; dasatinib; rapamycin