Therapy Detail

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Therapy Name Crizotinib + Cyclophosphamide + Topotecan
Synonyms
Therapy Description

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Drug Name Trade Name Synonyms Drug Classes Drug Description
Crizotinib Xalkori PF-02341066 ALK Inhibitor 25 MET Inhibitor 54 RON Inhibitor 10 ROS1 Inhibitor 15 Xalkori (crizotinib), inhibits ALK kinase, ALK fusion proteins, c-Met, ROS1 fusion proteins, and MST1R (RON), resulting in growth inhibition of tumor cells (PMID: 26951079, PMID: 22617245). Xalkori (crizotinib) is FDA approved for use in patients with ALK or ROS1 positive (rearrangements and fusions) non-small cell lung cancer, and in pediatric patients 1 year and older and young adults with relapsed or refractory, ALK-positive systemic anaplastic large cell lymphoma (FDA.gov).
Cyclophosphamide Cytoxan CPM Chemotherapy - Alkylating 16 Cytoxan (cyclophosphamide) is an alkylating agent, which inhibits DNA replication (NCI Drug Dictionary). Cytoxan (cyclophosphamide) is FDA approved in multiple hematological malignancies, breast cancer, neuroblastoma, ovarian cancer, and retinoblastoma (NCI Drug Dictionary).
Topotecan Hycamtin Topotecan Hcl Topotecan binds to topoisomerase I and stablizes complexes with DNA, resulting in decreased repair of DNA single-strand breaks, and potentially leading to cell death (NCI Drug Dictionary).

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
ALK act mut TP53 wild-type neuroblastoma predicted - sensitive Crizotinib + Cyclophosphamide + Topotecan Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Xalkori (crizotinib), Topotecan, and Cytoxan (cyclophosphamide) synergized to delay tumor growth in xenograft models of a human neuroblastoma cell line harboring constitutively phosphorylated wild-type Alk and wild-type TP53 (PMID: 26438783). 26438783
ALK F1174L neuroblastoma no benefit Crizotinib + Cyclophosphamide + Topotecan Case Reports/Case Series Actionable In a clinical case study, combination treatment with Xalkori (crizotinib), Cytoxan (cyclophosphamide), and Topotecan resulted in progressive disease within 1 cycle of therapy in a pediatric patient with metastatic, relapsed neuroblastoma harboring ALK F1147L and PIK3CA C692Ffs*8 (PMID: 34210658). 34210658
ALK wild-type TP53 C176F neuroblastoma no benefit Crizotinib + Cyclophosphamide + Topotecan Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) did not demonstrate synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) on growth inhibition in neuroblastoma cell lines harboring wild-tpye Alk and TP53 C176F in culture (PMID: 26438783). 26438783
ALK wild-type TP53 P177T neuroblastoma no benefit Crizotinib + Cyclophosphamide + Topotecan Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) did not demonstrate synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) on growth inhibition in neuroblastoma cell lines harboring wild-tpye Alk and TP53 P177T in culture (PMID: 26438783). 26438783
ALK amp TP53 wild-type neuroblastoma sensitive Crizotinib + Cyclophosphamide + Topotecan Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) demonstrated synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) in neuroblastoma cell lines harboring Alk amplification and functional TP53, resulting in growth inhibition in culture (PMID: 26438783). 26438783
ALK wild-type TP53 mut neuroblastoma no benefit Crizotinib + Cyclophosphamide + Topotecan Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) did not demonstrate synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) on growth inhibition in neuroblastoma cell lines harboring wild-tpye Alk and TP53 mutations in culture (PMID: 26438783). 26438783
ALK F1174L TP53 wild-type neuroblastoma sensitive Crizotinib + Cyclophosphamide + Topotecan Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Xalkori (crizotinib), Topotecan, and Cytoxan (cyclophosphamide) synergized to sustain tumor regression in xenograft models of a crizotinib-resistant human neuroblastoma cell line harboring ALK F1174L and wild-type TP53 (PMID: 26438783). 26438783
ALK mut TP53 wild-type neuroblastoma sensitive Crizotinib + Cyclophosphamide + Topotecan Preclinical - Pdx & cell culture Actionable In a preclinical study, Xalkori (crizotinib) demonstrated synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) in patient-derived neuroblastoma cell lines harboring Alk mutations and functional TP53, resulting in growth inhibition in culture and tumor regression in animal models (PMID: 26438783). 26438783
ALK F1245C TP53 wild-type neuroblastoma sensitive Crizotinib + Cyclophosphamide + Topotecan Preclinical - Pdx Actionable In a preclinical study, Xalkori (crizotinib) worked synergistically with Topotecan and Cytoxan (cyclophosphamide), resulting in sustained tumor regression in crizotinib-resistant neuroblastoma PDX models harboring ALK F1245C and wild-type Tp53 (PMID: 26438783). 26438783
ALK wild-type TP53 H168R neuroblastoma no benefit Crizotinib + Cyclophosphamide + Topotecan Preclinical - Cell line xenograft Actionable In a preclinical study, Xalkori (crizotinib) did not improve the effect of Topotecan and Cytoxan (cyclophosphamide) on tumor growth suppression in xenograft models of a human neuroblastoma cell line harboring wild-type ALK and TP53 H168R (PMID: 26438783). 26438783
ALK wild-type TP53 wild-type neuroblastoma no benefit Crizotinib + Cyclophosphamide + Topotecan Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) did not demonstrate synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) on growth inhibition in neuroblastoma cell lines harboring wild-tpye Alk and wild-type TP53 in culture (PMID: 26438783). 26438783
ALK R1275Q neuroblastoma sensitive Crizotinib + Cyclophosphamide + Topotecan Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Xalkori (crizotinib), Topotecan, and Cytoxan (cyclophosphamide) synergized to sustain tumor regression in human neuroblastoma cell line xenograft models harboring ALK R1275Q and wild-type TP53 (PMID: 26438783). 26438783

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Sorting

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Clinical Trial Phase Therapies Title Recruitment Status Covered Countries Other Countries


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