Virtual Library

Start Your Search

M.Q. Baggstrom



Author of

  • +

    P2.07 - Poster Session/ Small Cell Lung Cancer (ID 222)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Small Cell Lung Cancer
    • Presentations: 1
    • +

      P2.07-008 - CTC 11-001: PhI Study of Carfilzomib (C) + Irinotecan (I) in Relapsed, Irinotecan Sensitive Solid Tumors (ID 241)

      09:30 - 09:30  |  Author(s): M.Q. Baggstrom

      • Abstract
      • Slides

      Background:
      Inactivation of proteasome function allows for increased apoptosis and the potential for enhanced antitumor effect by chemotherapy. Carfilzomib (C) and Irinotecan (I) potentially synergize by increasing camptothecin-induced apoptosis and interfering with topoisomerase-I degradation, preventing DNA damage repair. This report describes the initial phase I study of C + I in adults with relapsed, irinotecan-sensitive cancers including small cell lung cancer (SCLC).

      Methods:
      The primary endpoint was determination of the MTD of 28-day cycle 1 of I (D1,8,15) and C (D1,2,8,9,15,16) using a standard 3+3 Ph1 design. Toxicity and response were evaluated using NCI CTCAE (v4) and RECIST (v1.1). Pharmacodynamics endpoints (proteasome activity, topo-1 expression, and gamma-H2AX protein expression in PBMC) were assessed on C1D1 and C1D2.

      Results:
      16 patients were enrolled at 3 dose levels of C (mg/m2/d) using stepped-up dosing: 20 mg given C1D1 & C1D2 then increased to the dose indicated: 20/27 (N=4), 20/36 (N=9), 20/45 (N=3) and I dosed at 125 mg/m2d. Median age: 64 (range 56-78), 8 M/8F. Tumor types included: SCLC (N=13), non-small cell lung cancer (NSCLC) (N=2) and ovarian (N=1). 6 subjects completed 2 or more cycles of therapy, 4 subjects were not evaluable for dose-limiting toxicity (DLT) secondary to rapid progressive disease (PD) or withdrawal and were replaced. 2 DLTs were observed in cohort 3, Grade (Gr)4 thrombocytopenia lasting ≥ 7 days and Gr3 diarrhea lasting ≥ 7 days) and 1 DLT in cohort 2 (Gr3 diarrhea lasting > 7 days). Serious adverse events (SAEs) by dose level: 20/27: Gr3 Dysphagia and recurrent laryngeal nerve palsy, (unrelated); Gr3 peripheral motor neuropathy and Gr3 urinary incontinence, (unrelated); 20/36: Gr3 fatigue, multiple occurrences; Gr3 diarrhea with dehydration; Gr3 cholelithiasis with dehydration (unrelated); 20/45: Gr3 dehydration, Gr3 anemia, Gr2 anemia and Gr3 acute on chronic kidney disease. Common Gr3/4 AEs were: fatigue (19%), thrombocytopenia (19%), diarrhea (13%), anemia (6%), neutropenia (6%), and leukopenia (6%). One patient (25%), five patients (55%), and two patients (67%) experienced Gr3/4 AEs in cohorts 1, 2, and 3, respectively. The maximum tolerated dose was exceeded at 20/45. Antitumor activity (stable disease or better) was observed in 3 SCLC subjects to date, with updated follow-up to be reported.

      Conclusion:
      C and I is a well-tolerated combination with anti-tumor activity in heavily pretreated patients. The recommended phase 2 dose of Carfilzomib is 20/36 mg/m2/d in combination with Irinotecan 125 mg/m2/d. A phase 2 study in SCLC is ongoing through the Lung Cancer Research Team (LCRT). This study was supported by Onyx Pharmaceuticals, a subsidiary of Amgen Corporation. Clinical trial information: NCT01941316.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.