Table 1

Clinical trials of radiotherapy and immunotherapy

IdentifierPhaseNTitleDiseaseInterventionsRadiation detailsPrimary outcomeSecondary outcomes
Not yet recruiting
NCT03932409I20Frontline Immunotherapy Combined With Radiation and Chemotherapy in High Risk Endometrial Cancer (FIERCE)High and intermediate-risk endometrial cancer Pembrolizumab given 1 week before CRT (paclitaxel every 3 weeks for 3 cycles)Vaginal cuff brachytherapyProportion of patients completing 3 cycles of pembrolizumabPFS; OS; AE frequency
Recruiting
NCT03738228I40Atezolizumab Before and/or With Chemoradiotherapy in Immune System Activation in Patients With Node-Positive Stage IB2, II, IIIB, or IVA Cervical CancerNode-positive stage IB2, II, IIIB, or IVA cervical cancer Atezolizumab q3w starting −21 days before standard cisplatin-based CRT; atezolizumab q3w starting at day 0 before standard cisplastin-based CRTEBRT once daily for 25 fractions with image guided brachytherapy beginning in weeks 4, 5, or at the end of EBRTT-cell receptor β clonal expansion in peripheral bloodIncidence of DLTs; frequency and severity of adverse events; T-cell receptor clonality, diversity and frequency; PD-L1 expression in tissue
NCT03955978I12TSR-042 in Addition to Standard of Care Definitive Radiation for Inoperable Endometrial CancerMedically inoperable FIGO clinical stage I or II endometrial carcinoma TSR-042 given over 4 doses: first dose given 21 days before first brachytherapy fraction, second at time of first fraction, third dose at time of fourth fraction, final dose 1 week after sixth fractionBrachytherapy 36 Gy in 6 fractions, given weeklyAE at 6 weeksPFS
NCT03452332I18Stereotactic Body Radiation Therapy, Tremelimumab and Durvalumab in Treating Participants With Recurrent or Metastatic Cervical, Vaginal, or Vulvar CancersRecurrent or metastatic cervical, vaginal, or vulvar cancers Tremelimumab + durvalumab q4w×4 cycles, followed by durvalumab alone for up to 8 cycles in absence of progression or severe toxicity; SABR on days 8, 10, 12 of cycle 1SABR with 3 fractions separated by 48 hoursAEResponse to treatment; PFS; OS; TTNT
NCT03277482I32Durvalumab, Tremelimumab+Radiotherapy in Gynecologic CancerMetastatic or unresectable endometrial, ovarian (ovarian epithelial, fallopian tube, primary peritoneal), cervical, vaginal, or vulvar cancer Tremelimumab and durvulumab taken together every 4 weeks for 4 cycles, durvalumab continued further for 13 cycles or until disease progression, concurrent radiotherapy to start with first day of immmunotherapy; durvalumab q4w for 13 cycles or until progression with concurrent radiotherapyHypofractionated short course (either 1 or 5 days)MTDORR; LRR, LCR, ARR, RD; PFS, OS
NCT03298893I/II21Nivolumab in Association With Radiotherapy and Cisplatin in Locally Advanced Cervical Cancers Followed by Adjuvant Nivolumab for up to 6 Months (NiCOL)Locally advanced cervical cancer (FIGO stage IB2–IVA) Nivolumab every 2 weeks with concurrent CRT followed by 5 months of nivolumab aloneIMRT (including VMAT) at 45 Gy in 25 fractions with an additionally 54 Gy in 25 fractions to positive nodes; optional lateral pelvic dose to cover target volumeDLT (within 11 weeks after treatment start)ORR; PFS; DFS; AE incidence; retrospective exome, RNA, and targeted sequence analysis; ctDNA heterogeneity; tumor micro-environment description; tumor PD-L1 immunohistochemistry
NCT03527264II24BrUOG 355: Nivolumab to Tailored Radiation Therapy With Concomitant Cisplatin in the Treatment of Patients With Cervical CancerLocally advanced cervical cancer (FIGO stage IB–IVA) Nivolumab q2w for 3 cycles starting at day 0 with concurrent CRT; nivolumab maintenance every 4 weeks after following CRT for 2 years; concurrent nivolumab with CRT (q2w for 3 cycles) and maintenance (every 4 weeks for 2 years)45 Gy in 25 fractions, whole pelvis or extended fieldAE within 6 months of treatment; AE within 30 days of treatment; PFS
NCT03192059II43Study of Pembrolizumab, Radiation and Immune Modulatory Cocktail in Cervical/Uterine Cancer (PRIMMO)Advanced or refractory cervical cancer, endometrial carcinoma, or uterine sarcomaAn immunomodulatory cocktail consisting of vitamin D (2000 IU), aspirin (325 mg), cyclophosphamide (50 mg), and 180 or 30 mg lansoprazole alternating weekly) plus curcumin with pembrolizumab every 3 weeks and RTEBRT 24 Gy in 3 fractions, a fraction every 28 hoursORRIncidence of AE; best OR; PFS; median PFS; OS; median OS; HR-QoL
NCT02635360II88A Randomized Phase II Study of Chemoradiation and Pembrolizumab for Locally Advanced CancerAdvanced cervical cancerStandard cisplatin-based CRT with concurrent pembrolizumab; standard cisplatin based CRT followed by pembrolizumab every 3 weeks4–6 fractions of brachytherapyChange in immunologic markers; DLTsMetabolic response rate on imaging; incidence of distant metastases; PFS; OS
NCT03614949II26SBRT and Atezolizumab in the Management of Recurrent, Persistent, or Metastatic Cervical CancerRecurrent or metastatic cervical cancer Atezolizumab q3w 1 week following SBRT therapySBRT with 24 Gy in 3 fractionsORRPFS; OS
NCT03830866III714Study of Durvalumab With Chemoradiotherapy for Women With Locally Advanced Cervical CancerLocally advanced cervical cancer Durvalumab every 4 weeks and standard-of-care CRT followed by durvalumab monotherapy; placebo and CRTEBRT and brachytherapy (standard-of-care)PFSOS; CR; PR; ORR; DoR in patients with CR; HR-QoL; PFS 3 years; AE, safety and tolerability (ECGs, vital signs, chemistry and hematology panels)
Active, not recruiting
NCT03312114II29Anti-PD-L1 and SABR for Ovarian CancerMetastatic fallopian tube cancer, primary peritoneal carcinoma, recurrent epithelial cancer of ovary Avelumab Stereotactic treatment (eg, SABR/SBRT)ORROS; CR; TTP; median response duration
  • AE, adverse event; ARR, abscopal response rate; CR, complete response; CRT, chemo-radiation therapy; DLT, dose-limiting toxicity; DoR, duration of response; EBRT, external-beam radiation therapy; ECG, electrocardiogram; FIGO, International Federation of Obstetrics and Gynecology; HR-QoL, health-related quality of life; IMRT, intensity-modulated radiation therapy; LCR, local control rate; LRR, local-regional recurrence; ORR, overall response rate; OS, overall survival; PD-L1, programmed death-ligand 1; PFS, progression-free survival; q2w, once every 2 weeks; q3w, once every 3 weeks; q4w, once every 4 weeks; RD, response duration; SABR, stereotactic ablative radiation therapy; SBRT, stereotactic body radiation therapy ; TTNT, time to next treatment; TTP, time to progression; VMAT, volumetric modulated arc therapy.