| General information |
| Database: | DB00690 |
| Objective: | This study assessed the safety, pharmacokinetics (PK), and tolerability of humanized IGF1R antibody AVE1642 with other cancer treatments. |
| Authors: | Macaulay VM, et al |
| Title: | Phase I study of humanized monoclonal antibody AVE1642 directed against the type 1 insulinlike growth factor receptor (IGF1R), administered in combination with anticancer therapies to patients with advanced solid tumors. |
| Journal: | Ann Oncol. |
| Year: | 2013 |
| PMID: | 23104723 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | AVE1642
|
| Target: | Type 1 insulinlike growth factor receptor
|
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | an uncontrolled, fourarm multicenter study |
| Key Patients Feature: | To be eligible, patients were required to have pathologically confirmedadvanced stage of solid tumor, one of the combination therapies should bea reasonable option given tumor characteristics and prior therapy, andprovided no grade more than and equal to 3 toxic effects occurred during previous treatment withcompounds in the same class. The specific inclusion criteria were age more than and equal to 18years, Eastern Cooperative Oncology Group (ECOG) performance status 0-2, at least one measurable or evaluable lesion, and adequate hematologic, hepatic, and renal function (Hb more than and equal to 9 g/dl, neutrophils more than and equal to 1.5 ¡Á 109/l, plateletsmore than and equal to 100 ¡Á 109/l, creatinine <1.5¡Á upper limit of normal (ULN) or calculatedcreatinine clearance more than and equal to 60 ml/min, bilirubin less than and equal to ULN, AST/SGOT and ALT/SGPT less than and equal to 2.5¡Á ULN (less than and equal to 5¡Á ULN if liver metastases), and alkaline phosphataseless than and equal to 2.5¡Á ULN (less than and equal to 5¡Á ULN if bone or liver metastases). Patients in thedoxorubicin cohort were required to have left ventricular ejection fraction(LVEF) more than and equal to 50% within 1 month before the trial entry. Patients were excludedfor brain metastases, peripheral neuropathy grade more than and equal to 2, pregnancy/lactation, HbA1c >8% within 2 months of inclusion, >2 prior lines of cytotoxicchemotherapy or >4 prior lines of therapy in total (including targetedagents) for advanced disease, known severe hypersensitivity to docetaxel orother drugs formulated in polysorbate 80, or any other contraindication tothe selected combination therapy. |
| Biomarker: | Blood samples were assayed for PK, IGFs, and IGFBP3. |
| Biomark Analysis: | On treatment IGFII rose by 68 ¡À 25 ng/ml in patients discontinuing treatment <12 weeks, and fell by 55.5 ¡À 21 ng/ml with disease control (P < 0.001). |
| Control Group Info: | single arm |
| Treatment Info: | pts received three weekly AVE1642 dosed at 6 mg/kg, chosen following previous study, with 75 (cohort A) or 100 mg/m(2) (B) docetaxel, 1250 mg/m(2) gemcitabine/100 mg erlotinib (C1), or 60 mg/m(2) doxorubicin (D1). |
| Primary End Point: | MTD, DLTs, tumor response and toxicity |
| Secondary End Point: | NA |
| Patients Number: | 58 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | There were three partial responses in cohorts B (melanoma) and C (leiomyosarcoma, two cases) and 22 stabilizations more than and equal to 12 weeks, giving a control rate of 25/57 (44%). On treatment IGFII rose by 68 ¡À 25 ng/ml in patients discontinuing treatment <12 weeks, and fell by 55.5 ¡À 21 ng/ml with disease control (P < 0.001). |
| Disease Control Rate: | NA |
| Median Time to Progression: | 21 weeks (range 12-56 weeks) in cohort A, 28.5 weeks (range 12-48.3 weeks) in cohort B, and 48 weeks (range 21-71) in cohort C. |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The commonest adverse events were diarrhea (37/58 patients), asthenia (34/58), nausea (30/58), and stomatitis (21/58). Grade 3-4 hyperglycemia (three cases) accompanied steroid premedication for docetaxel administration. |
| Conclusions: | AVE1642 was tolerable with 75100 mg/m(2) docetaxel and 1000 mg/m(2) gemcitabine75 mg erlotinib, achieving durable disease control in 44%, with an association bettheyen IGFII and response. |