Microbiome and Rectal Cancer

Rectal Cancer Clinical Trial

Official title:

Rectal Microbiome Variability Among Rectal Cancer Cohorts Including Complete Clinical Responders, Pathologic Responders, and Early Recurrence

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04223102
• Other study ID #: Pro00040924
• Status: Active, not recruiting
• Phase: N/A
• Start date: February 18, 2020
• Est. completion date: June 2027

Study information

• Verified date: July 2023
• Source: University of South Florida
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of our study is to determine if an association exists between the microbiome of those with rectal adenocarcinoma who are complete pathologic responders and those who have a partial or no response to neoadjuvant therapy.

Description:

This study will help to further elucidate the association of bacteria with rectal cancer, while also characterizing the genes associated with that risk. Furthermore it will attempt to better understand which patients may have an optimal response to neoadjuvant chemoradiation allowing for possible predictive metagenomics evaluation, investigators may be able to augment treatments as well as provide recommendations for the success and cost effectiveness of cancer care.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 40
• Est. completion date: June 2027
• Est. primary completion date: January 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age = 18 years old

• Locally Advanced Rectal Adenocarcinoma (T3)

• Standard 5FU based chemoradiation

• Total Neoadjuvant Therapy per OPRA protocol guidelines

Exclusion Criteria:

• Age < 18 years

• Stage I or Stage IV rectal adenocarcinoma

• Rectal cancer other than adenocarcinoma

• Genetically associated cancer (HNPCC, FAP etc.) or highly suspicious for genetically associated cancer

• Prior history of rectal adenocarcinoma (i.e. recurrent colorectal adenocarcinoma)

Related Conditions & MeSH terms

• Locally Advanced Malignant Neoplasm
• Neoplasms
• Rectal Cancer
• Rectal Neoplasms

Intervention

Procedure:
• Tissue collection
A flexible sigmoidoscopy is a procedure in which a flexible tubularized camera approximately 1 cm in diameter is inserted into the anus and advanced proximally to the sigmoid colon (approximately 20 cm). At that time a rectal biopsy of the tumor will be obtained as well as a sample from >5cm proximal to the tumor, with a separate biopsy forcep. Tattoo injection, as standard of care, will be performed within 1 cm distal to the tumor to identify the location in the future or for surgical intervention. If there is inability to get proximal to the tumor then a location at least 5 cm adjacent in any direction will be sufficient so long as it is grossly normal appearing.

Locations

Country	Name	City	State
United States	Tampa General Hospital	Tampa	Florida
United States	University of South Florida	Tampa	Florida
United States	University of South Florida - South Tampa Campus	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
University of South Florida

Country where clinical trial is conducted

United States, 

References & Publications (35)

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Garcia-Aguilar J, Chow OS, Smith DD, Marcet JE, Cataldo PA, Varma MG, Kumar AS, Oommen S, Coutsoftides T, Hunt SR, Stamos MJ, Ternent CA, Herzig DO, Fichera A, Polite BN, Dietz DW, Patil S, Avila K; Timing of Rectal Cancer Response to Chemoradiation Conso — View Citation

Gerassy-Vainberg S, Blatt A, Danin-Poleg Y, Gershovich K, Sabo E, Nevelsky A, Daniel S, Dahan A, Ziv O, Dheer R, Abreu MT, Koren O, Kashi Y, Chowers Y. Radiation induces proinflammatory dysbiosis: transmission of inflammatory susceptibility by host cytokine induction. Gut. 2018 Jan;67(1):97-107. doi: 10.1136/gutjnl-2017-313789. Epub 2017 Apr 24. — View Citation

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Kasai C, Sugimoto K, Moritani I, Tanaka J, Oya Y, Inoue H, Tameda M, Shiraki K, Ito M, Takei Y, Takase K. Comparison of human gut microbiota in control subjects and patients with colorectal carcinoma in adenoma: Terminal restriction fragment length polymo — View Citation

Kostic AD, Chun E, Robertson L, Glickman JN, Gallini CA, Michaud M, Clancy TE, Chung DC, Lochhead P, Hold GL, El-Omar EM, Brenner D, Fuchs CS, Meyerson M, Garrett WS. Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-imm — View Citation

Kwong TNY, Wang X, Nakatsu G, Chow TC, Tipoe T, Dai RZW, Tsoi KKK, Wong MCS, Tse G, Chan MTV, Chan FKL, Ng SC, Wu JCY, Wu WKK, Yu J, Sung JJY, Wong SH. Association Between Bacteremia From Specific Microbes and Subsequent Diagnosis of Colorectal Cancer. Ga — View Citation

Liu L, Tabung FK, Zhang X, Nowak JA, Qian ZR, Hamada T, Nevo D, Bullman S, Mima K, Kosumi K, da Silva A, Song M, Cao Y, Twombly TS, Shi Y, Liu H, Gu M, Koh H, Li W, Du C, Chen Y, Li C, Li W, Mehta RS, Wu K, Wang M, Kostic AD, Giannakis M, Garrett WS, Hutt — View Citation

Maas M, Nelemans PJ, Valentini V, Das P, Rodel C, Kuo LJ, Calvo FA, Garcia-Aguilar J, Glynne-Jones R, Haustermans K, Mohiuddin M, Pucciarelli S, Small W Jr, Suarez J, Theodoropoulos G, Biondo S, Beets-Tan RG, Beets GL. Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data. Lancet Oncol. 2010 Sep;11(9):835-44. doi: 10.1016/S1470-2045(10)70172-8. Epub 2010 Aug 6. — View Citation

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McCoy AN, Araujo-Perez F, Azcarate-Peril A, Yeh JJ, Sandler RS, Keku TO. Fusobacterium is associated with colorectal adenomas. PLoS One. 2013;8(1):e53653. doi: 10.1371/journal.pone.0053653. Epub 2013 Jan 15. — View Citation

Mima K, Cao Y, Chan AT, Qian ZR, Nowak JA, Masugi Y, Shi Y, Song M, da Silva A, Gu M, Li W, Hamada T, Kosumi K, Hanyuda A, Liu L, Kostic AD, Giannakis M, Bullman S, Brennan CA, Milner DA, Baba H, Garraway LA, Meyerhardt JA, Garrett WS, Huttenhower C, Meye — View Citation

Mima K, Nishihara R, Qian ZR, Cao Y, Sukawa Y, Nowak JA, Yang J, Dou R, Masugi Y, Song M, Kostic AD, Giannakis M, Bullman S, Milner DA, Baba H, Giovannucci EL, Garraway LA, Freeman GJ, Dranoff G, Garrett WS, Huttenhower C, Meyerson M, Meyerhardt JA, Chan — View Citation

Mima K, Sukawa Y, Nishihara R, Qian ZR, Yamauchi M, Inamura K, Kim SA, Masuda A, Nowak JA, Nosho K, Kostic AD, Giannakis M, Watanabe H, Bullman S, Milner DA, Harris CC, Giovannucci E, Garraway LA, Freeman GJ, Dranoff G, Chan AT, Garrett WS, Huttenhower C, — View Citation

NIH HMP Working Group; Peterson J, Garges S, Giovanni M, McInnes P, Wang L, Schloss JA, Bonazzi V, McEwen JE, Wetterstrand KA, Deal C, Baker CC, Di Francesco V, Howcroft TK, Karp RW, Lunsford RD, Wellington CR, Belachew T, Wright M, Giblin C, David H, Mills M, Salomon R, Mullins C, Akolkar B, Begg L, Davis C, Grandison L, Humble M, Khalsa J, Little AR, Peavy H, Pontzer C, Portnoy M, Sayre MH, Starke-Reed P, Zakhari S, Read J, Watson B, Guyer M. The NIH Human Microbiome Project. Genome Res. 2009 Dec;19(12):2317-23. doi: 10.1101/gr.096651.109. Epub 2009 Oct 9. — View Citation

Peters BA, Wu J, Pei Z, Yang L, Purdue MP, Freedman ND, Jacobs EJ, Gapstur SM, Hayes RB, Ahn J. Oral Microbiome Composition Reflects Prospective Risk for Esophageal Cancers. Cancer Res. 2017 Dec 1;77(23):6777-6787. doi: 10.1158/0008-5472.CAN-17-1296. — View Citation

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Sanapareddy N, Legge RM, Jovov B, McCoy A, Burcal L, Araujo-Perez F, Randall TA, Galanko J, Benson A, Sandler RS, Rawls JF, Abdo Z, Fodor AA, Keku TO. Increased rectal microbial richness is associated with the presence of colorectal adenomas in humans. IS — View Citation

Sears CL. The who, where and how of fusobacteria and colon cancer. Elife. 2018 Mar 13;7:e28434. doi: 10.7554/eLife.28434. — View Citation

Smith JD, Ruby JA, Goodman KA, Saltz LB, Guillem JG, Weiser MR, Temple LK, Nash GM, Paty PB. Nonoperative management of rectal cancer with complete clinical response after neoadjuvant therapy. Ann Surg. 2012 Dec;256(6):965-72. doi: 10.1097/SLA.0b013e3182759f1c. — View Citation

Smith JJ, Chow OS, Gollub MJ, Nash GM, Temple LK, Weiser MR, Guillem JG, Paty PB, Avila K, Garcia-Aguilar J; Rectal Cancer Consortium. Organ Preservation in Rectal Adenocarcinoma: a phase II randomized controlled trial evaluating 3-year disease-free survival in patients with locally advanced rectal cancer treated with chemoradiation plus induction or consolidation chemotherapy, and total mesorectal excision or nonoperative management. BMC Cancer. 2015 Oct 23;15:767. doi: 10.1186/s12885-015-1632-z. — View Citation

Thomas AM, Jesus EC, Lopes A, Aguiar S Jr, Begnami MD, Rocha RM, Carpinetti PA, Camargo AA, Hoffmann C, Freitas HC, Silva IT, Nunes DN, Setubal JC, Dias-Neto E. Tissue-Associated Bacterial Alterations in Rectal Carcinoma Patients Revealed by 16S rRNA Comm — View Citation

Wirbel J, Pyl PT, Kartal E, Zych K, Kashani A, Milanese A, Fleck JS, Voigt AY, Palleja A, Ponnudurai R, Sunagawa S, Coelho LP, Schrotz-King P, Vogtmann E, Habermann N, Nimeus E, Thomas AM, Manghi P, Gandini S, Serrano D, Mizutani S, Shiroma H, Shiba S, Sh — View Citation

Wong SH, Kwong TNY, Chow TC, Luk AKC, Dai RZW, Nakatsu G, Lam TYT, Zhang L, Wu JCY, Chan FKL, Ng SSM, Wong MCS, Ng SC, Wu WKK, Yu J, Sung JJY. Quantitation of faecal Fusobacterium improves faecal immunochemical test in detecting advanced colorectal neopla — View Citation

Xu K, Jiang B. Analysis of Mucosa-Associated Microbiota in Colorectal Cancer. Med Sci Monit. 2017 Sep 14;23:4422-4430. doi: 10.12659/msm.904220. — View Citation

Yang Y, Weng W, Peng J, Hong L, Yang L, Toiyama Y, Gao R, Liu M, Yin M, Pan C, Li H, Guo B, Zhu Q, Wei Q, Moyer MP, Wang P, Cai S, Goel A, Qin H, Ma Y. Fusobacterium nucleatum Increases Proliferation of Colorectal Cancer Cells and Tumor Development in Mic — View Citation

Yoon H, Kim N, Park JH, Kim YS, Lee J, Kim HW, Choi YJ, Shin CM, Park YS, Lee DH, Jung HC. Comparisons of Gut Microbiota Among Healthy Control, Patients With Conventional Adenoma, Sessile Serrated Adenoma, and Colorectal Cancer. J Cancer Prev. 2017 Jun;22 — View Citation

* Note: There are 35 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	16s rRNA gene sequencing to study bacterial phylogeny and taxonomy	16s rRNA sequencing from biopsy specimens	5 years
Secondary	rectal microbiota to study bacteria strains	rectal microbiota - bacteria strains from biopsy specimens	5 years