Table 2.
Clinical trials of vintafolide (EC145) in ovarian cancer
| Study, year, reference | Phase | Patient population (n, cancer type) | Chemotherapy status | Dosing schedule | Disease status, n (%) | PFS | Toxicities (grade 3–4), n (%) | ||
|---|---|---|---|---|---|---|---|---|---|
| Sausville et al, 200783 | I | 32, solid tumors (including OC) | Chemo-refractory | Arm 1: bolus injection Arm 2: 1-hour infusion (D1, 3, 5 and D15, 17, 19 of each 28 D cycle) |
OC, n=2/32 SD, 1 (50%) PD, 1 (50%) |
NA | Constipation Fatigue Neuropathy |
Arm 1: 2 (6%) 1 (3%) 0 (0%) |
Arm 2: 2 (6%) 1 (3%) 1 (3%) |
| Naumann et al, 200984 | II | 49 OPFC | Recurrent | EC145 iv on MWF of W1, 3 (4 W cycle) | PR, 3 (6%) (DCR = CR + PR + SD) at 8 W 40.8% (20/49) | NA | Constipation Fatigue Nausea |
14 (28%) 10 (20%) 8 (16%) |
|
| Naumann et al, 201344 | II | 149 OC | PL-resistant recurrent | Arm 1: PLD 50 mg/m2 iv, D1+ EC145 2.5 mg iv, W1–3 q28 Arm 2: PLD 50 mg/m2 iv, D1 q28 days |
NA | Arm 1: 5.1 M Arm 2: 2.7 M Arm 1 (FR+): 5.5 M Arm 2 (FR+): 1.5 M |
Anemia Neutropenia Leucopenia Febrile/neutropenia Thrombocytopenia Fatigue Constipation Neuropathy Stomatitis Erythrodysesthesia |
Arm 1: 9 (6%) 9 (6%) 23 (15%) 1 (0.5%) 4 (2%) 9 (6%) 2 (1%) 4 (2%) 8 (5%) 11 (7%) |
Arm 2: 8 (5%) 0 (0%) 10 (6%) 2 (1%) 4 (2%) 6 (4%) 0 (0%) 0 (0%) 4 (2%) 2 (1%) |
|
NCT01170650 PROCEED Study, 2014 (ongoing)86,* |
III | 640 OC (500/640 FR+) | PL-resistant | Arm 1: EC145 iv bolus on D1, 3, 5 and D15, 17, 19 of a 4 W cycle + PLD 50 mg/m2 every 4 W Arm 2: PLD 50 mg/m2 every 4 W + placebo |
Ongoing | Ongoing | Ongoing | ||
Notes:
OS was a secondary endpoint, and in this trial, no difference was noted between treatment arms. The multivariate analysis, after adjusting for baseline imbalances, suggested an overall survival benefit for the vintafolide plus PLD versus PLD arm in the FR 100% subpopulation (hazard ratio =0.481; 95% confidence interval =0.169–1.370; P=0.171).
Abbreviations: CR, complete response; D, day; DCR, disease-control rate; FR+, folate receptor-positive disease; iv, intravenous; NA, not available; OC: ovarian cancer; OPFC, primary peritoneal, fallopian tube cancer; M, months; MWF, Monday-Wednesday-Friday; PD, progressive disease; PFS, progression-free survival; PLD, pegylated liposomal doxorubicin; PR, partial response; SD, stable disease; W, week; PL, platinum; OS, overall survival.