Phase 1 and 2 study of carboplatin and pralatrexate in patients with recurrent, platinum‐sensitive ovarian, fallopian tube, or primary peritoneal cancer

• Published in: Cancer Vol. 122; no. 21; pp. 3297 - 3306
• Main Authors: del Carmen, Marcela G., Supko, Jeff G., Horick, Nora K., Rauh‐Hain, J. Alejandro, Clark, Rachel M., Campos, Susana M., Krasner, Carolyn N., Atkinson, Tina, Birrer, Michael J.
• Format: Journal Article
• Language: English
• Published: United States 01.11.2016
• Subjects: Adult; Aged; Aminopterin - administration & dosage; Aminopterin - analogs & derivatives; Antineoplastic Combined Chemotherapy Protocols - pharmacokinetics; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Carboplatin - administration & dosage; carboplatin‐pralatrexate; Carcinoma, Transitional Cell - drug therapy; Carcinoma, Transitional Cell - pathology; Carcinosarcoma - drug therapy; Carcinosarcoma - pathology; chemotherapy; Cystadenocarcinoma, Serous - drug therapy; Cystadenocarcinoma, Serous - pathology; Endometrial Neoplasms - drug therapy; Endometrial Neoplasms - pathology; Fallopian Tube Neoplasms - drug therapy; Fallopian Tube Neoplasms - pathology; Female; Follow-Up Studies; Humans; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - pathology; Neoplasm Staging; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - pathology; Peritoneal Neoplasms - drug therapy; Peritoneal Neoplasms - pathology; pharmacokinetics; Prognosis; recurrent ovarian cancer; Survival Rate; Tissue Distribution; pharmacokinetics; chemotherapy; carboplatin-pralatrexate; recurrent ovarian cancer
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.30196

BACKGROUND The objective of this phase 1 and 2 trial was to identify the appropriate dose of combined carboplatin and pralatrexate for patients with recurrent, platinum‐sensitive ovarian, fallopian tube, and primary peritoneal cancer. METHODS In phase 1, patients received carboplatin (at an area under the curve of 5) and increasing doses of pralatrexate until the maximum‐tolerated dose (MTD) of pralatrexate was achieved. The primary endpoint was the response rate. Additional endpoints were safety, response duration, progression‐free survival, overall survival, and pharmacokinetics. RESULTS Thirty patients were enrolled in phase 1, and 20 were enrolled in phase 2. Of all 50 patients, 49 completed the study. The mean patient age was 59 years, and patients completed a median of 6 cycles. The MTD for pralatrexate was 105 mg/m2. The clinical benefit rate (complete responses plus partial responses plus stable disease) was 86%. Of 26 patients who received the MTD, 12 had a partial response, 11 had stable disease, and 2 had disease progression. The progression‐free survival rate at 3 and 6 months was 87% and 79%, respectively; and the overall survival rate was 98% at 6 and 12 months and 66% at 24 months. Of 30 patients, 18 (60%) in phase 1 experienced an adverse event of any grade; and, of those, 4 patients (13%) had a grade 3 or greater adverse event. In phase 2, 12 patients (60%) had an adverse event of any grade, and 4 (20%) had grade 3 or greater toxicity. There was a significant reduction in the total body clearance of pralatrexate when it was received concurrently with carboplatin. CONCLUSIONS Most patients responded to carboplatin‐pralatrexate combination. This regimen is well tolerated and effective in this patient population. Cancer 2016;122:3297–3306. © 2016 American Cancer Society. In this phase 1 and 2 trial, the appropriate dose of carboplatin‐pralatrexate is identified in patients with recurrent, platinum‐sensitive ovarian, fallopian tube, and primary peritoneal cancer. Most patients respond to the carboplatin‐pralatrexate combination, and the regimen is well tolerated and effective in this population.