Table 2

Clinical trials of radiotherapy and DNA damage response inhibitors

IdentifierPhaseNTitleDiseaseInterventionsRadiation detailsPrimary outcomeSecondary outcomes
NCT03641547I65A 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 CRTPalliative radiotherapyBest tolerated treatment scheduleIncidence of AE; proportion of patients completing 75%, 90%, and 100% of radiotherapy dose; objective tumor response
NCT02223923I100A 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 radiotherapyPalliative radiotherapy (20 or 30 Gy)MTDIncidence of AE; single and multiple dose pharmacokinetics; tumor response
NCT03345784I33A Phase I Study of the Wee 1 Kinase (Wee 1) Inhibitor AZD1775 in Combination With Radiotherapy and Cisplatin in Cervical, Upper Vaginal and Uterine CancersCervical, vaginal, or uterine cancerDaily EBRT with adavosertib (daily or on days 1, 3, and 5) with weekly cisplatin for up to 5 weeksWhole pelvic radiotherapy to a total dose of 45 GyRecommended phase 2 dose (dose level with <1/6 of patients with DLT)ORR; pharmacodynamic effects (CKC2, Ki67, γH2AX, pH3, CC3 biomarkers); PFS; AE incidence
NCT03968406I24Phase I Study of Talazoparib in Combination With Radiation Therapy for Locally Recurrent Gynecologic CancersLocally 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 progressionRadiotherapy 5 days a week for up to 7 weeksMTDAE incidence; response rate; LCR; TTP; PFS; OS; level of PAR inhibition; γH2Ax and RAD51 foci formation; HR-QoL
NCT03644342I/II20Phase I/II Study of Niraparib With Radiotherapy for Treatment of Metastatic Invasive Carcinoma of the CervixDistant metastatic cervical cancer (FIGO stage IV)3–6 cycles of Induction-style carboplatin and paclitaxel followed by definitive pelvic radiotherapy with niraparib Whole pelvic radiotherapyMTD; local PFSAE profile; HR-QoL; tumor response
NCT02466971III348Radiation 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 CancerNewly 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 brachytherapyPFS, assessed up to 5 yearsOS (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.