Table 3.

16 ongoing clincal studies using medium-to-high dose IVC as anti-cancer therapy

Cancer type(s)	NCT Number	Allocation/ Phase	Interventions	Type of combination therapy	VitC IV dose*	VitC dose and administration schedule	Estimated enrollment	Primary outcome(s)
Colorectal	NCT04516681 [131]	Randomized, Phase 3	Arm 1: Ascorbic acid + chemotherapy Arm 2: Chemotherapy alone (FOLFOXIRI+/− bevacizumab)	Chemo + Targeted	high	1.5 g/kg/day, D1–3, every 2 weeks	400	Objective Response Rate
Colorectal, Pancreatic, Lung	NCT03146962 [73]	Single group, Phase 2	Cohort A: VitC for 2–4 consecutive weeks Cohort 2: VitC up to 6 months Cohort 3: VitC for 1–2 weeks prior to and following Y90 radioembolization of hepatic metastases	RE	high	1.25 g/kg for 4 days/week	50	Pathologic response (cohort A) 3-month disease control rate (DCR) (cohort B) Maximal tolerated dose (cohort C)
Hepatocellular, Pancreatic, Gastric, Colorectal	NCT04033107 [132]	Single group, Phase 2	VitC + metformin	Targeted	high	1.5 g/kg, D1–3, every 2 weeks	30	Progression-free survival
Lung	NCT02420314 [133]	Single group, Phase 2	Ascorbic acid + paclitaxel + carboplatin	Chemo	high	75 g, two times/week	57	Tumor response
Lung	NCT02905591 [134]	Single group, Phase 2	Ascorbate + chemoRT (radiation therapy + paclitaxel + carboplatin)	Chemo-RT	high	75 g, 3 times/week	46	Progression rate
Lymphoma	NCT03602235 [135]	Single group, Phase 1	VitC + melphalan	Chemo	high	50 g, 75 g and 100 g (3 + 3 cohort method)	9	Number of treatment related adverse events
Lymphoma	NCT03418038 [136]	Randomized, Phase 2	Arm 1: Ascorbic acid + combination chemotherapy Arm 2: Placebo + combination chemotherapy (rituximab + ifosfamide + carboplatin + etoposide D1–3; rituximab + cisplatin + cytarabine + dexamethasone if MR or SD after 2 courses) Arm 3: Ascorbic acid + combination chemotherapy (ifosfamide + carboplatin + etoposide or cisplatin + cytarabine + dexamethasone or gemcitabine + dexamethasone + cisplatin or gemcitabine + oxaliplatin or oxaliplatin + cytarabine + dexamethasone)	Chemo + Targeted + Corticosteroid	high	High dose (n.s.) on D1, 3, 5, 8, 10, 12, 15, 17 and 19, combination chemotherapy on D1–3; treatment repeats every 21 days for up to 4 courses	151	Overall response rate
Pancreatic	NCT02905578 [137]	Randomized, Phase 2	Arm 1: Ascorbate + chemotherapy Arm 2: Chemotherapy alone (gemcitabine + nab-paclitaxel)	Chemo	high	75 g, three times/weekly for 4 weeks	65	Overall survival
Pancreatic	NCT04150042 [138]	Single group, Phase 1	VitC + chemotherapy/stem cell treatment (melphalan + carmustine + vitamin B12B + ethanol)	Chemo + Dietary suppl.	high	Dose-escalation beginning with 3 g/m^2 and escalating to a maximum of 8 g/m^2	10	Rate of mucositis, rate of engraftment of Neutrophils + adverse events, among others
Pancreatic	NCT03410030 [139]	Single group, Phase 1/2	Ascorbic acid + nab-paclitaxel + cisplatin + gemcitabine	Chemo	high	≥ 20 mM plasma concentration	36	Phase IB: recommended phase II dose (to reach ≥20 mM) Phase II: disease control rate
Prostate	NCT02516670 [140]	Randomized, Phase 2	Arm 1: Ascorbate + Docetaxel Arm 2: Placebo + Docetaxel	Chemo	high	1 g/kg, 3 times/ week	69	Occurrence of PSA decline of > = 50% + adverse events
Renal Cell	NCT03334409 [141]	Randomized, Phase 2	Arm 1: Ascorbic acid + tyrosine kinase inhibitor Arm 2: Tyrosine kinase inhibitor alone (Pazopanib)	Targeted	high	1 g/kg 3 times/week	91	Treatment failure-free rate
Sarcoma	NCT04634227 [142]	Single group, Early phase 1	Ascorbate + gemcitabine	Chemo	high	75 g dose on D1–2, until target serum concentration between 20 and 30 mM (otherwise maximum dose of 125 g)	20	Progression-free survival
Sarcoma	NCT03508726 [143]	Single group, Phase 1/2	Ascorbate + radiation therapy	RT	high	75 g, three times/week	25	Incidence of dose limiting toxicities (DLTs) + tumor response
Bladder	NCT04046094 [74]	Single group, Phase 1/2	Ascorbic acid	–	medium	25 g, 2 times/week for 4 weeks	21	Post treatment pathological staging
Lung	NCT03799094 [144]	Randomized, Phase 1/2	Arm 1: VitC + tyrosine kinase inhibitor Arm 2: Tyrosine kinase inhibitor alone (osimertinib, erlotinib or gefitinib)	Targeted	medium	30 g once/week	150	Progression-free survival

Shown are the 16 trials using medium-to-high dose IVC out of a total 23 studies currently recruiting (status February 2021), as retrieved from the clinicaltrials.govdatabase (see also Fig. 3). Entries are ordered primarily by high-to-medium IVC dose, and secondarily by cancer type