Clinical trials of radiotherapy and DNA damage response inhibitors
| Identifier | Phase | N | Title | Disease | Interventions | Radiation details | Primary outcome | Secondary outcomes |
| Recruiting | ||||||||
| NCT03641547 | I | 65 | A Phase 1 Dose Escalation Safety Study Combining the ATR Inhibitor M6620 With Chemoradiotherapy in Oesophageal Cancer & Other Solid Cancers Using Time to Event Continual Reassessment Method (CHARIOT) | Adenocarcinoma or squamous cell carcinoma of the esophagus; advanced, metastatic, or unresectable solid tumor | M6620 (an ATR inhibitor) with radiotherapy; M6620 with chemotherapy; M6620 with CRT | Palliative radiotherapy | Best tolerated treatment schedule | Incidence of AE; proportion of patients completing 75%, 90%, and 100% of radiotherapy dose; objective tumor response |
| NCT02223923 | I | 100 | A Phase I Study to Assess the Tolerability, Safety and Biological Effects of ATR Inhibitor (AZD6738) as a Single Agent and in Combination With Palliative Radiation Therapy in Patients With Solid Tumours (Patriot) | Solid tumors refractory to conventional treatment | AZD6738 (an ATR inhibitor) alone and with radiotherapy | Palliative radiotherapy (20 or 30 Gy) | MTD | Incidence of AE; single and multiple dose pharmacokinetics; tumor response |
| NCT03345784 | I | 33 | A Phase I Study of the Wee 1 Kinase (Wee 1) Inhibitor AZD1775 in Combination With Radiotherapy and Cisplatin in Cervical, Upper Vaginal and Uterine Cancers | Cervical, vaginal, or uterine cancer | Daily EBRT with adavosertib (daily or on days 1, 3, and 5) with weekly cisplatin for up to 5 weeks | Whole pelvic radiotherapy to a total dose of 45 Gy | Recommended phase 2 dose (dose level with <1/6 of patients with DLT) | ORR; pharmacodynamic effects (CKC2, Ki67, γH2AX, pH3, CC3 biomarkers); PFS; AE incidence |
| NCT03968406 | I | 24 | Phase I Study of Talazoparib in Combination With Radiation Therapy for Locally Recurrent Gynecologic Cancers | Locally recurrent gynecologic cancers | Talazoparib on days −10 and −7 before radiotherapy and concurrent with radiotherapy unless unacceptable toxicity, continuing for up to 8 weeks in the absence of disease progression | Radiotherapy 5 days a week for up to 7 weeks | MTD | AE incidence; response rate; LCR; TTP; PFS; OS; level of PAR inhibition; γH2Ax and RAD51 foci formation; HR-QoL |
| NCT03644342 | I/II | 20 | Phase I/II Study of Niraparib With Radiotherapy for Treatment of Metastatic Invasive Carcinoma of the Cervix | Distant metastatic cervical cancer (FIGO stage IV) | 3–6 cycles of Induction-style carboplatin and paclitaxel followed by definitive pelvic radiotherapy with niraparib | Whole pelvic radiotherapy | MTD; local PFS | AE profile; HR-QoL; tumor response |
| NCT02466971 | III | 348 | Radiation Therapy and Cisplatin With or Without Triapine in Treating Patients With Newly Diagnosed Stage IB2, II, or IIIB–IVA Cervical Cancer or Stage II–IVA Vaginal Cancer | Newly diagnosed AJCC v6 and v7 stage IB2, stage II, IIIB, or IVA cancer of the uterine cervix or stage II–IVA vaginal cancer | Triapine (IV over 2 hours on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33) in addition to CRT (cisplatin-based) | EBRT in 25 fractions followed by LDR or HDR brachytherapy | PFS, assessed up to 5 years | OS (assessed up to 5 years); metabolic complete response; acute and chronic AEs, compliance |
AE, adverse event; AJCC, American Joint Committee on Cancer; ATR, ataxia telangiectasia and Rad3 related; CRT, chemo-radiation therapy; DLT, dose-limiting toxicity; EBRT, external-beam radiation therapy; FIGO, International Federation of Obstetrics and Gynecology; HDR, high dose rate; HR-QoL, health-related quality of life; IV, intravenously; LDR, low dose rate; LRC, local-regional control; MTD, maximum tolerated dose; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; TTP, time to progression.