| General information |
| Database: | DB00219 |
| Objective: | Thisphase I/II study in patients with metastatic castrationresistant prostate cancer (mCRPC) explored ipilimumab as monotherapy and in combination with radiotherapy, based on the preclinical evidence of synergistic antitumor activity between antiCTLA4 antibody and radiotherapy. |
| Authors: | Slovin SF, et al |
| Title: | Ipilimumab alone or in combination with radiotherapy in metastatic castrationresistant prostate cancer: results from an openlabel, multicenterphase I/II study. |
| Journal: | Ann Oncol |
| Year: | 2013 |
| PMID: | 23535954 |
| Trial Design |
| Clinical Trial Id: | NCT00323882 |
| Agent: | ipilimumab
|
| Target: | Cytotoxic Tlymphocyte antigen 4 (CTLA4)
|
| Cancer Type: | prostate cancer |
| Cancer Subtype: | advanced castrationresistant prostate cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 12 |
| Therapeutic Combination Content: | Ipilimumab+radiotherapy |
| Study Type: | a phase I/II, nonrandomized, openlabel, multicenter study |
| Key Patients Feature: | Men diagnosed with mCRPC (rising PSA or progression on scans with a serum testosterone concentration of <50 ng/dl) and the evidence of progression after the discontinuation of antiandrogen therapy who had no more than one prior chemotherapy were enrolled |
| Biomarker: | PSA |
| Biomark Analysis: | Serum prostatespecific antigen levels were prospectively monitored as a biomarker for cancer activity. |
| Control Group Info: | ipilimumab as monotherapy versus in combination with radiotherapy |
| Treatment Info: | In dose escalation, 33 patients (more than and equal to 6/cohort) received ipilimumab every 3 weeks ¡Á 4 doses at 3, 5, or 10 mg/kg or at 3 or 10 mg/kg + radiotherapy (8 Gy/lesion). The 10mg/kg cohorts were expanded to 50 patients (ipilimumab monotherapy, 16; ipilimumab + radiotherapy, 34). |
| Primary End Point: | adverse events (AEs), prostatespecific antigen (PSA) decline, and tumor response. |
| Secondary End Point: | NA |
| Patients Number: | 75 |
| Trial Results |
| DLT_MTD: | There were no DLTs during the 5week assessment period. Since the MTD was not reached, ipilimumab 10 mg/kg ¡À XRT cohorts were expanded by 38 patients to 50 forphase II evaluation. |
| Objective Response Rate: | Among patients receiving 10 mg/kg ¡À radiotherapy, eight had PSA declines of more than and equal to 50% (duration: 313+ months), one had complete response (duration: 11.3+ months), and six had stable disease (duration: 2.86.1 months). |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | 52 deaths reported across all cohorts (n = 71), the median OS by the Kaplan-Meier analysis was 17.4 months (95% CI: 11.5-24.7). |
| Adverse Event(agent arm): | Common immunerelated AEs (irAEs) among the 50 patients receiving 10 mg/kg ¡À radiotherapy were diarrhea (54%), colitis (22%), rash (32%), and pruritus (20%); grade 3/4 irAEs included colitis (16%) and hepatitis (10%). One treatmentrelated death (5 mg/kg group) occurred. |
| Conclusions: | In mCRPC patients, ipilimumab 10 mgkg ¡À radiotherapy suggested clinical antitumor activity with disease control and manageable AEs. Twophase III trials in mCRPC patients evaluating ipilimumab 10 mgkg ¡À radiotherapy are ongoing. |