Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

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Rare Diseases

Small Cell Lung Carcinoma

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Small Cell Lung Cancer

Antineoplastic Agents

All Drugs and Chemicals

Gastrointestinal Agents

Carboplatin

Etoposide

Etoposide phosphate

Rabeprazole

Enzyme Inhibitors

Antacids

Anti-Ulcer Agents

Proton Pump Inhibitors

Phase II:Participants will receive AL3810 orally in combination with carboplatin and etoposide during the Cycles 1-4 . AL3810 dose escalated form 5mg to 10mg step-up to determine the recommended dose of AL3810 in combination with carboplatin plus (+) etoposide in untreated participants with ES-SCLC.

Phase III:Participants will receive AL3810(recommended dose will be determined by safety monitoring committee (SMC) in Phase II) orally in combination with carboplatin and etoposide during the Cycles 1-4. Thereafter, participants will receive maintenance AL3810 until persistent radiographic PD, intolerable toxicity or withdrawal of consent, investigator's consideration, lost follow up, death ,study termination by the sponsor.whichever occurs first.

Phase III:Participants will receive placebo orally in combination with carboplatin and etoposide during the induction Cycles 1-4. Thereafter, participants will receive maintenance placebo until persistent radiographic PD, intolerable toxicity or withdrawal of consent, investigator's consideration, lost follow up, death ,study termination by the sponsor.whichever occurs first.

AL3810

Carboplatin and etoposide are background treatment.

carboplatin + etoposide

Placebo

Yixing Chen

Baohui Han, M.D

Phase II Study is to Evaluate the Safety and tolerability of AL3810 in combination with carboplatin plus (+) etoposide in untreated participants with ES-SCLC.

Phase III Study is to Evaluate the efficacy of AL3810 in combination with carboplatin plus (+) etoposide in untreated participants with ES-SCLC.

This Phase II/III, Multicenter Study is Designed to Evaluate the Safety and Clinical Activity of AL3810 in Patients

Multicenter, Phase II/III Study of Carboplatin Plus Etoposide With AL3810 in Participants With Untreated Extensive-Stage (ES) Small Cell Lung Cancer (SCLC)

AE/SAE to find the recommended dose of AL3810

1. Duration of Progression-Free Survival (PFS) as Assessed by the Independent Review Committee Using RECIST v1.1

Haihe Biopharma Co., Ltd.

Medulloblastoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antirheumatic Agents

Irinotecan

Cyclophosphamide

Temozolomide

Busulfan

Thiotepa

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Topoisomerase I Inhibitors

Carboplatin + etoposide then thiotepa then Cyclophosphamide + Busilvex. If insufficient response: TEMIRI + etoposide/radiotherapy + temozolomide

Carboplatin 160 mg/m\^2 Day 1 to day 5, as an intravenous infusion over 1 hour. Dilution in 5 % glucose saline or sodium chloride 9 mg/ml (0.9%).

Etoposide 100 mg/m\^2 D ay 1 to day 5, as an intravenous infusion over 1 hour. Dilution in physiological saline or 5 % glucose saline while not exceeding a concentration of 0.4 mg/ml etoposide in the infusion bottle.

Carboplatin + etoposide

Thiotepa 200 mg/m² Day-3 to day-1, as an intravenously infusion over 1 hour dilution in 200 ml/m\^2 of 5% glucose saline or sodium chloride 9 mg/ml (0.9%).

Cyclophosphamide:

* Level 1 20 mg/kg/day
* Level 2 30 mg/kg/day
* Level 3 40 mg/kg/day
* Level 4 50 mg/kg/day

Busilvex:

\< 9 kgs 0.8 mg/kg/dose -\> 3.2 mg/kg/day; 9 à \< 16 kgs 0.96 mg/kg/dose -\> 3.84 mg/kg/day; 16 à 23 kgs 0.88 mg/kg/dose -\> 3.52 mg/kg/day; \> 23 à 34 kgs 0.76 mg/kg/dose -\> 3.04 mg/kg/day; \> 34 kgs -\> 0.64 mg/kg/dose.

Cyclophosphamide + Busilvex

During 2 cycles of 21 days:

* Temozolomide: 100 mg/m\^2/day PO from Day 1 to Day 5;
* Irinotecan: 10 mg/m\^2/day IV from Day 1 to Day 5 + from Day 8 to Day 12

Temozolimide + Irinotecan

* Etoposide: 35 mg/m\^2/day PO during 21days
* Radiotherapy: 1.8 Gy/fraction/day (total dose: 54 Gy)

Etoposide + radiotherapy

150 mg/m\^2/day PO during 5 days, during 6 cycles of 21 days

Christelle Dufour, MD

The trial includes i) the evaluation of the efficacy of a treatment strategy, designed as a phase II trial, and ii) a dose-finding part.

The Phase II trial is an open label, non-randomized, multicentre trial without control group. A Bayesian approach will be used to analyse the EFS, assuming a cure model. We will use three prior distributions of the EFS; (1) an enthusiastic prior distribution, (2) a pessimistic prior distribution, and (3) a non-informative prior distribution. As the patient outcomes in the trial will be recorded, the subsequent distribution of the outcome probability under experimental treatment will be computed by applying Bayes' theorem, which yields an estimated EFS probability with a 95% credibility interval (measure of Bayesian precision). Two interim analyses are planned to monitor the efficacy data (early stopping rules for futility or inefficacy).

The final analysis of efficacy will be made on an intention to treat basis, including all recruited patients, 3 years after recruitment of the last patient.

Due to the uncertainty on the dose of cyclophosphamide that can be given in combination with Busilvex for the last chemotherapy course in patients in complete response after intensification chemotherapy treatment, a dose-finding subtrial will be performed to address this issue (Phase I part). The dose escalation of cyclophosphamide will be performed using the Continual Reassessment Method in a Bayesian framework.

Study of Sequential High-dose Chemotherapy in Children With High Risk Medulloblastoma

Phase I / II Study of Sequential High-dose Chemotherapy With Stem Cell Support in Children Younger Than 5 Years of Age With High-risk Medulloblastoma

To determine the Maximum Tolerated Dose (MTD) of cyclophosphamide in combination with a fixed dose of Busilvex in children with high-risk medulloblastoma who are in complete response after the intensification phase.

To assess the efficacy in terms of Event Free Survival (EFS) of the strategy intended to treat children younger than 5 years of age suffering from high-risk medulloblastoma with sequential high-dose chemotherapy without radiotherapy.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
This Phase II/III, Multicenter Study is Designed to Evaluate the Safety and Clinical Activity of AL3810 in Patients	NCT04254471	Extensive-stage...	AL3810 carboplatin + e... Placebo	18 Years - 75 Years	Haihe Biopharma Co., Ltd.
Study of Sequential High-dose Chemotherapy in Children With High Risk Medulloblastoma	NCT02025881	High-risk Medul...	Carboplatin + e... Thiotepa Cyclophosphamid... Temozolimide + ... Etoposide + rad... Temozolomide	- 5 Years	Gustave Roussy, Cancer Campus, Grand Paris
Study of Sequential High-dose Chemotherapy in Children With High Risk Medulloblastoma	NCT02025881	High-risk Medul...	Carboplatin + e... Thiotepa Cyclophosphamid... Temozolimide + ... Etoposide + rad... Temozolomide	- 5 Years	Gustave Roussy, Cancer Campus, Grand Paris
This Phase II/III, Multicenter Study is Designed to Evaluate the Safety and Clinical Activity of AL3810 in Patients	NCT04254471	Extensive-stage...	AL3810 carboplatin + e... Placebo	18 Years - 75 Years	Haihe Biopharma Co., Ltd.

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