TABLE 2.
Drugs that target cell pathways in CRC‐SCs and are tested in clinical trials as anti‐CRC agents*
| ID | Study Title | Conditions | Interventions | Phase | First Posted | Current Status |
|---|---|---|---|---|---|---|
| NCT01304602 | A trial of irinotecan and BKM120 in previously treated advanced colorectal cancer | Colorectal cancer |
Drug: Irinotecan Drug: BKM120 |
Phase 1 | February 25, 2011 | Completed |
| NCT01591421 | PI3Kinase inhibitor BKM120 in combination with panitumumab in metastatic/advanced RAS‐wild type colorectal cancer | Metastatic colorectal cancer |
Drug: BKM120 Drug: Panitumumab |
Phase 1 Phase 2 |
May 4, 2012 | Completed |
| NCT01571024 | BKM120 + mFOLFOX6 in advanced solid tumors with expansion cohort pancreatic cancer |
Advanced solid tumors Metastatic colorectal cancer Metastatic pancreatic cancer |
Drug: BKM120 Drug: mFOLFOX6 |
Phase 1 | April 4, 2012 | Completed |
| NCT01501604 | BKM120 in cancers with PIK3CA activating mutations |
Lung cancer Breast cancer Colorectal cancer Cholangiocarcinoma Solid tumors |
Drug: BKM120 | Phase 2 | December 29, 2011 | Withdrawn (the study has been closed due to lack of accrual) |
| NCT01576666 | Phase Ib, dose‐escalation study of oral LDE225 in combination with BKM120 in patients with advanced solid tumors |
Dose escalation Safety Preliminary efficacy Advanced solid tumors, including metastatic colorectal cancer |
Drug: LDE225 Drug: BKM120 |
Phase 1 | April 12, 2012 | Completed |
| NCT02439385 | Avastin/FOLFIRI in combination with curcumin in colorectal cancer patients with unresectable metastasis | Colorectal cancer |
Drug: Avastin/FOLFIRI Dietary supplement: Curcumin |
Phase 2 | May 8, 2015 | Completed |
| NCT00973869 | Curcumin in preventing colorectal cancer in patients undergoing colorectal endoscopy or colorectal surgery | Colorectal cancer | Dietary supplement: curcumin | Phase 1 | September 9, 2009 | Unknown |
| NCT01859858 | Effect of curcumin on dose‐limiting toxicity and pharmacokinetics of irinotecan in patients with solid tumors | Advanced colorectal cancer |
Dietary supplement: curcumin Drug: irinotecan |
Phase 1 | May 22, 2013 | Completed |
| NCT01333917 | Curcumin biomarkers | Colorectal cancer | Drug: Curcumin C3 tablet | Phase 1 | April 12, 2011 | Completed |
| NCT01490996 | Combining curcumin with FOLFOX chemotherapy in patients with inoperable colorectal cancer | Colonic cancer metastasis |
Drug: Oral complex C3 curcumin + chemotherapy Drug: Chemotherapy only |
Phase 1 Phase 2 |
December 13, 2011 | Completed |
| NCT00027495 | Curcumin for the prevention of colon cancer | Colorectal cancer | Dietary supplement: curcumin | Phase 1 | January 27, 2003 | Completed |
| NCT00003365 | Sulindac and plant compounds in preventing colon cancer | Colorectal cancer |
Dietary supplement: curcumin Dietary Supplement: rutin Drug: quercetin Drug: sulindac |
Not applicable | May 21, 2004 | Terminated (study completed) |
| NCT00118989 | Curcumin for the chemoprevention of colorectal cancer | Adenomatous polyps | Dietary Supplement: curcuminoids | Not applicable | July 12, 2005 | Terminated (could not be completed due to technical problems and cost constraints) |
| NCT00003365 | Sulindac and plant compounds in preventing colon cancer | Colorectal cancer |
Dietary supplement: curcumin Dietary supplement: rutin Drug: quercetin Drug: sulindac |
Not applicable | May 21, 2004 | Terminated (study completed) |
| NCT02891538 | Chemopreventive effects of epigallocatechin gallatein colorectal cancerpatients | Colon cancer | Drug: epigallocatechin gallate | Early phase 1 | September 7, 2016 | Recruiting |
| NCT02321969 | Green tea extracts for the prevention of colorectal adenomas and colorectal cancer | Neoplasms, colorectal | Dietary supplement: green tea extract | Not applicable | December 22, 2014 | Completed |
| NCT01941953 | Metformin and 5‐fluorouracil for refractory colorectal cancer | Metastatic colorectal cancer | Drug: Metformin and 5‐Fluorouracil | Phase 2 | September 13, 2013 | Completed |
| NCT02614339 | Effect of adjunctive metformin on recurrence of non‐DM colorectal cancer stage II high‐risk/III colorectal cancer |
Non‐DM stage II high‐risk colorectal cancer Non‐DM stage III colorectal cancer |
Drug: Metformin Drug: Control |
Phase 3 | November 25, 2015 | Recruiting |
| NCT01816659 | An open‐labeled pilot study of biomarker response following short‐term exposure to metformin | Colorectal carcinoma | Metformin extended release | Phase 1 | March 22, 2013 | Terminated (slow accrual) |
| NCT01312467 | Trial of metformin for colorectal cancer risk reduction for a history of colorectal adenomas and elevated BMI |
Adenomatous polyp Colorectal cancer Obesity |
Drug: Metformin hydrochloride | Phase 2 | June 25, 2015 | Completed |
| NCT01926769 | A phase II study to determine the safety and efficacy of second‐line treatment with metformin and chemotherapy (FOLFOX6 or FOFIRI) in the second line treatment of advanced colorectal cancer | Previously treated advanced colorectal cancer | Drug: Metformin | Phase 2 | August 21, 2013 | Terminated (slow accrual rate) |
| NCT01523639 | A randomized, placebo‐controlled, double‐blind phase II study evaluating if glucophage can avoid liver injury due to chemotherapy‐associated steatosis |
Colorectal cancer steatohepatitis |
Drug: Metformin/Placebo | Phase 2 | February 1, 2012 | Terminated (prematurely due to slow recruitment) |
| NCT03800602 | Nivolumab and metformin in patients with treatment‐refractory MSS colorectal cancer | Colorectal neoplasms |
Drug: Metformin Biological: Nivolumab |
Phase 2 | January 11, 2019 | Active, not recruiting |
| NCT01930864 | Metformin plus irinotecan for refractory colorectal cancer | Colorectal Neoplasms Adenocarcinoma |
Drug: Metformin Drug: Irinotecan |
Phase 2 | August 29, 2013 | Unknown |
| NCT03047837 | A randomized, 2×2 factorial design biomarker prevention trial of low‐dose aspirin and metformin in stage I‐III colorectal cancer patients | Tertiary prevention in colon cancer |
Drug: Aspirin + Metformin Drug: Aspirin Drug: Metformin Drug: Placebos |
Phase 2 | February 9, 2017 | Unknown |
| NCT01440127 | Impact of pretreatment with metformin on colorectal cancer stem cells and related pharmacodynamic markers | Colon cancer | Drug: Metformin | Phase 1 | September 26, 2011 | Terminated (unable to accrue all planned subjects in a timely fashion, but data collected will be analyzed) |
| NCT01340300 | Exercise and metformin in colorectal and breast cancer survivors |
Colorectal cancer Breast cancer |
Behavioral: Exercise training Drug: Metformin Other: Educational information |
Phase 2 | September 18, 2017 | Completed |
| NCT04033107 | High dose vitamin C combined with metformin in the treatment of malignant tumors |
Hepatocellular cancer Pancreatic cancer Gastric cancer Colorectal cancer |
Drug: Vitamin C Drug: Metformin |
Phase 2 | July 25, 2019 | Recruiting |
| NCT01632020 | Effect of metformin on biomarkers of colorectal tumor cell growth | Colorectal neoplasms |
Drug: Placebo Drug: Metformin |
Phase 2 | June 29, 2012 | Terminated (inadequate accrual) |
| NCT01333475 | MK‐2206 and AZD6244 in patients with advanced colorectal carcinoma | Colorectal neoplasms | Drug: MK‐2206 + AZD6244 | Phase 2 | April 12, 2011 | Completed |
| NCT01186705 | Clinical and translational study of MK‐2206 in patients with metastatic KRAS‐wild‐type, PIK3CA‐mutated, colorectal cancer |
Colon cancer Rectal cancer |
Drug: MK‐2206 | Phase 2 | August 23, 2010 | Terminated (lack of accrual) |
| NCT01802320 | Akt inhibitor MK‐2206 in treating patients with previously treated colon or rectal cancer that is metastatic or locally advanced and cannot be removed by surgery | Colorectal neoplasms |
Drug: Akt Inhibitor MK‐2206 Other: Laboratory Biomarker Analysis Other: Pharmacological Study |
Phase 2 | March 1, 2013 | Completed |
| NCT01243762 | A study of dalotuzumab + MK‐2206, dalotuzumab + MK‐0752, and dalotuzumab + ridaforolimus combination therapies in participants with advanced cancer (MK‐0646‐027) | Neoplasms malignant |
Drug: dalotuzumab Drug: MK‐0752 Drug: ridaforolimus Drug: MK‐2206 |
Phase 1 | November 19, 2010 | Terminated (the study was terminated for business reasons and not due to any safety or efficacy concerns related to dalotuzumab) |
| NCT03522649 | A Phase III clinical study of napabucasin (GB201) Plus FOLFIRI in adult patients with metastatic colorectal cancer | Previously treated metastatic colorectal cancer |
Drug: Napabucasin Drug: Fluorouracil Drug: Leucovorin Drug: Irinotecan |
Phase 3 | May 11, 2018 | Recruiting |
| NCT02753127 | A study of napabucasin (BBI‐608) in combination with FOLFIRI in adult patients with previously treated metastatic colorectal cancer (CanStem303C) | Colorectal cancer |
Drug: Napabucasin Drug: Fluorouracil Drug: Leucovorin Drug: Irinotecan Drug: Bevacizumab |
Phase 3 | April 27, 2016 | Completed |
| NCT01776307 | A study of BBI608 in adult patients with advanced colorectal cancer | Colorectal cancer |
Drug: BBI608 Drug: Panitumumab Drug: Capecitabine Drug: Cetuximab |
Phase 2 | January 28, 2013 | Completed |
| NCT01830621 | BBI608 and best supportive care vs placebo and best supportive care in pretreated advanced colorectal carcinoma | Colorectal carcinoma |
Drug: BBI608 Drug: Placebo Other: Best supportive care |
Phase 3 | April 12, 2013 | Completed |
| NCT02641873 | A study of BBI608 administered with FOLFIRI + bevacizumab in adult patients with metastatic colorectal cancer | Metastatic colorectal cancer |
Drug: BBI608 Drug: 5‐FU Drug: Irinotecan Drug: Levofolinate Drug: Bevacizumab |
Phase 1 | December 30, 2015 | Completed |
| NCT03647839 | Modulation of the tumor microenvironment using either vascular disrupting agents or STAT3 inhibition in order to synergize with PD1 inhibition in microsatellite stable, refractory colorectal cancer (MODULATE) | Colorectal cancer metastatic |
Drug: Nivolumab 10 MG/ML Drug: BNC 105 Drug: BBI608 |
Phase 2 | August 27, 2018 | Completed |
| NCT02851004 | A special combination of BBI608 and pembrolizumab | Metastatic colorectal cancer |
Drug: BBI608 (Napabucasin) Drug: Pembrolizumab |
Phase 1 Phase 2 |
August 1, 2016 | Terminated (on the request of the investigational drug provider) |
| NCT01606124 | Polyphenon E in treating patients with high‐risk of colorectal cancer | Advanced colorectal adenomas adenocarcinoma of the colon stage I colon cancer stage II colon cancer stage III colon cancer |
Drug: defined green tea catechin extract Other: placebo Other: questionnaire administration Other: laboratory biomarker analysis |
Phase 2 | May 25, 2012 | Terminated (pending expiration of the supply of study agent) |
| NCT03439462 | ABI‐009 (Nab‐rapamycin) in combination with FOLFOX and Bevacizumab as first‐line therapy in patients with advanced or metastatic colorectal cancer | Colorectal cancer metastatic | Drug: ABI‐009; nab‐rapamycin; albumin‐bound rapamycin |
Phase 1 Phase 2 |
February 20, 2018 | Recruiting |
| NCT00409994 | Safety study of rapamycin administered before and during radiotherapy to treat rectum cancer | Rectum cancer | Drug: Rapamycin |
Phase 1 Phase 2 |
December 12, 2006 | Completed |
| NCT03190174 | Nivolumab (Opdivo®) plus ABI‐009 (Nab‐rapamycin) for advanced sarcoma and certain cancers | Colorectal cancer and other cancers |
Drug: Nab‐Rapamycin Biological: Nivolumab |
Phase 1 Phase 2 |
June 16, 2017 | Recruiting |
| NCT01522820 | Vaccine therapy with or without sirolimus in treating patients with NY‐ESO‐1 expressing solid tumors |
Recurrent colorectal carcinoma Others cancers |
Biological: DEC‐205/NY‐ESO‐1 Fusion Protein CDX‐1401 Other: Laboratory Biomarker Analysis Other: Pharmacological Study Drug: Sirolimus |
Phase 1 | February 1, 2012 | Completed |
| NCT00375245 | Rapamycin with grapefruit juice for advanced malignancies |
Tumors Neoplasm metastasis |
Drug: rapamycin (sirolimus) Other: grapefruit juice |
Phase 1 | September 12, 2006 | Completed |
| NCT02465060 | Targeted therapy directed by genetic testing in treating patients with advanced refractory solid tumors, lymphomas, or multiple myeloma (the match screening trial) | Many tumors, including colorectal cancer and recurrent colorectal cancer | Many targeted drugs, including taselisib and vismodegib | Phase 2 | June 8, 2015 | Recruiting |
| NCT00636610 | A study of vismodegib (GDC‐0449, hedgehog pathway inhibitor) with concurrent chemotherapy and bevacizumab as first‐line therapy for metastatic colorectal cancer | Metastatic colorectal cancer |
Drug: Vismodegib 150 mg Drug: Placebo to vismodegib Drug: Bevacizumab Drug: Modified FOLFOX Drug: FOLFIRI |
Phase 2 | March 14, 2008 | Completed |
| NCT00959647 | A study of vismodegib (GDC‐0449) in patients treated with vismodegib in a previous Genentech‐sponsored phase I or II cancer study |
Ovarian cancer Basal cell carcinoma Metastatic colorectal cancer |
Drug: Vismodegib Drug: FOLFOX Drug: FOLFIRI Drug: Bevacizumab |
Phase 2 | August 14, 2009 | Completed |
*All studies were accessed at www.clinicaltrials.gov on August 28, 2021 by using the search term “CRC” and the drugs that are presented in Table 1.
Abbreviations: CRC‐SCs, colorectal cancer stem cells; BMI, body mass index; DM, diabetes mellitus; FOLFIRI, 5‐fluorouracil, leucovorin plus irinotecan; FOLFOX, 5‐fluorouracil, folic acid plus oxaliplatin; FOLFOX6, 5‐fluorouracil, leucovorin plus oxaliplatin; MSS, microsatellite stable; PI3Kinase, phosphatidyl‐inositol‐3‐kinase; PIK3CA, phosphatidylinositol‐4,5‐bisphosphate 3‐kinase catalytic subunit alpha.