Postoperative Chemoradiation or Chemotherapy After Preoperative Chemotherapy for Gastric Cancers

NCT03515941 | Terminated Early Phase 1 Results DMC FDA Drug

• 1 other identifier: H-40682
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 4

Brief Summary

This is an open-label, stratified, two arm design. All patients receive same initial standard preoperative chemotherapy and surgical resection. Patients will then be assigned to either standard postoperative chemotherapy if node negative at surgery or standard postoperative chemoradiation if node positive at surgery. The primary objective of this study is to determine the feasibility of patients enrolling and receiving either postoperative chemoradiation or chemotherapy alone, based upon nodal status at surgery, following preoperative chemotherapy. The secondary Objectives is to evaluate the rate of cancer recurrence in patients assigned to treatment based upon node status. To explore the potential correlation between changes in expression of a pre-specified panel of genes identified as relevant to gastrointestinal cancers in response to preoperative chemotherapy, using presence of nodal involvement at time of surgery as an indicator of response.

Conditions

Gastrointestinal Cancer

Keywords

chemotherapy; chemoradiation

Outcome Measures

Primary Outcomes (1)

• Number of Participants Who Complete the Recommended Therapy From Each Arm

  The number of patients who complete the recommended therapy will be counted for each arm.

  From date of assigned therapy up to 17 weeks

Secondary Outcomes (1)

• Median Time to Recurrence

  From the end of completion of assigned therapy, subjects undergo follow-up every 3 months for a total of 36 months(planned) after the date of surgery or until the study closure

Study Arms (2)

Arm 1: Adjuvant Chemotherapy

EXPERIMENTAL

Three cycles of chemo with CAPEOX (Oxaliplatin:130 mg/m2 by IV and Capecitabine: 625 or 1000 mg/m2 by PO (BID) on 21 day-cycle or FOLFOX (Oxaliplatin:85 mg/m2 by IV, Leucovorin:400 mg/m2 by IV,5-fluorouracil: 400 mg/m2 and 2400 mg/m2 by IV) on 14 day-cycle

Drug: Oxaliplatin; Drug: Capecitabine; Drug: Leucovorin; Drug: 5-fluorouracil

Arm 2: Adjuvant Chemoradiation

EXPERIMENTAL

Three cycles of chemo with Capecitabine: 750 mg/m2 by PO BID on days 1-14 of a 28 day-cycle or 5-fluorouracil (Leucovorin:400 mg/m2 by IV,5-fluorouracil: 400 mg/m2 and 1200 mg/m2 by IV) on days 1 and 15 of a 28 day cycle After 1st chemo cycle above, chemoradiation for 5 weeks with 45 Gy in 1.8 Gy/fraction, 5 days a week, to the entire gastric bed (including anastomosis) and draining lymph nodes, and a single agent fluoropyrimidine, either capecitabine or 5-fluorouracil After 5 weeks chemoradiation, 2 cycles of chemo as described above.

Drug: Capecitabine; Drug: Leucovorin; Drug: 5-fluorouracil; Radiation: radiation

Interventions

Oxaliplatin DRUG

130 mg/m2 by IV (Arm 1)

Also known as: Eloxatin

Arm 1: Adjuvant Chemotherapy

Capecitabine DRUG

625 mg/m2 (Arm 1), 1000 mg/m2 (Arm 1), 750 mg/m2 by PO (Arm 2)

Also known as: Xeloda

Arm 1: Adjuvant Chemotherapy; Arm 2: Adjuvant Chemoradiation

Leucovorin DRUG

400 mg/m2 by IV (Arm 1 \& Arm 2)

Also known as: Wellcovorin

Arm 1: Adjuvant Chemotherapy; Arm 2: Adjuvant Chemoradiation

5-fluorouracil DRUG

400, 2400 mg/m2 by IV (Arm 1), 400,1200 mg/m2 by IV (Arm 2)

Also known as: Adrucil

Arm 1: Adjuvant Chemotherapy; Arm 2: Adjuvant Chemoradiation

radiation RADIATION

45 Gy in 1.8 Gy/fraction

Arm 2: Adjuvant Chemoradiation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must have pathologically-proven adenocarcinoma of the stomach or gastroesophageal (GE)-junction, stage M0, as established by both imaging and surgical pathologic staging.
• Imaging: Clinical stage of M0 will be established by either CT (chest with contrast and abdomen/pelvis with and without contrast), or CT/PET (positron emission tomography) (skull base to mid-thigh). This is standard post-surgery imaging.
• Surgery: Surgical pathologic staging must be M0.
• Must have completed 3 cycles of neo-adjuvant chemotherapy. Either CAPEOX or FOLFOX is allowed. Dose modifications are allowed, but all 3 cycles must have been completed.
• Must have undergone a surgical resection with definitive intent, either by open or laparoscopic resection of the primary gastric or GE junction cancer. Patients must have undergone a total gastrectomy, subtotal gastrectomy, or distal gastrectomy (depending on the location of primary gastric lesion) with at least a modified D2 lymphadenectomy.
• Must be deemed as a good candidate for adjuvant chemotherapy or chemoradiation (to start within 3 months of surgery), in the opinion of the treating investigator. Plan must be to start adjuvant therapy within 90 days of surgery; adjuvant treatment cannot begin more than 90 days after surgery.
• Must have diagnostic biopsy tissue (pre-neoadjuvant chemo) available for genetic testing.
• Must have surgical tissue (post-neoadjuvant chemo) available for genetic testing.
• Must be \> 18 years of age.
• Must be able to provide informed consent.
• Must have adequate kidney, liver, and bone marrow function, within 28 days prior to registration, as follows:
• i. Hemoglobin ≥ 8.0 gm/dL
• ii. Absolute neutrophil count (ANC) ≥ 1500 cells/mm3
• iii. Platelet count ≥ 75,000 /mm3
• iv. Calculated creatinine clearance of \> 60 mL/min/m2, calculated as follows:

You may not qualify if:

• Other than the 3 cycles of neoadjuvant chemotherapy and surgery (mentioned above), must not have received other treatment for their gastric cancer.
• Female patients who are pregnant, breast feeding, or of childbearing potential without a negative pregnancy test prior to baseline. Women of childbearing potential must have a negative serum pregnancy test as a part of eligibility, within 28 days of registration.
• Patients unwilling or unable to comply with the protocol, or provide informed consent.
• Patients with clinical evidence of metastatic disease.
• Any medical condition that, in the opinion of the investigator, would exclude the patient from participating in this study and treatment plan.

Sponsors & Collaborators

• Tannaz Armaghany: lead

Study Sites (4)

Baylor College of Medicine Medical Center - McNair Campus

Houston, Texas, 77030, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Baylor St. Lukes Medical Center

Houston, Texas, 77030, United States

Location

Harris Health System- Smith Clinic

Houston, Texas, 77054, United States

Location

Related Publications (9)

• Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, Scarffe JH, Lofts FJ, Falk SJ, Iveson TJ, Smith DB, Langley RE, Verma M, Weeden S, Chua YJ, MAGIC Trial Participants. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006 Jul 6;355(1):11-20. doi: 10.1056/NEJMoa055531.

  PMID: 16822992 BACKGROUND

• Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, Haller DG, Ajani JA, Gunderson LL, Jessup JM, Martenson JA. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001 Sep 6;345(10):725-30. doi: 10.1056/NEJMoa010187.

  PMID: 11547741 BACKGROUND

• Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, Middleton G, Daniel F, Oates J, Norman AR; Upper Gastrointestinal Clinical Studies Group of the National Cancer Research Institute of the United Kingdom. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008 Jan 3;358(1):36-46. doi: 10.1056/NEJMoa073149.

  PMID: 18172173 BACKGROUND

• Ychou M, Boige V, Pignon JP, Conroy T, Bouche O, Lebreton G, Ducourtieux M, Bedenne L, Fabre JM, Saint-Aubert B, Geneve J, Lasser P, Rougier P. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol. 2011 May 1;29(13):1715-21. doi: 10.1200/JCO.2010.33.0597. Epub 2011 Mar 28.

  PMID: 21444866 BACKGROUND

• Enzinger PC, Burtness BA, Niedzwiecki D, Ye X, Douglas K, Ilson DH, Villaflor VM, Cohen SJ, Mayer RJ, Venook A, Benson AB 3rd, Goldberg RM. CALGB 80403 (Alliance)/E1206: A Randomized Phase II Study of Three Chemotherapy Regimens Plus Cetuximab in Metastatic Esophageal and Gastroesophageal Junction Cancers. J Clin Oncol. 2016 Aug 10;34(23):2736-42. doi: 10.1200/JCO.2015.65.5092. Epub 2016 Jul 5.

  PMID: 27382098 BACKGROUND

• Dikken JL, van Sandick JW, Maurits Swellengrebel HA, Lind PA, Putter H, Jansen EP, Boot H, van Grieken NC, van de Velde CJ, Verheij M, Cats A. Neo-adjuvant chemotherapy followed by surgery and chemotherapy or by surgery and chemoradiotherapy for patients with resectable gastric cancer (CRITICS). BMC Cancer. 2011 Aug 2;11:329. doi: 10.1186/1471-2407-11-329.

  PMID: 21810227 BACKGROUND

• Smyth EC, Fassan M, Cunningham D, Allum WH, Okines AF, Lampis A, Hahne JC, Rugge M, Peckitt C, Nankivell M, Langley R, Ghidini M, Braconi C, Wotherspoon A, Grabsch HI, Valeri N. Effect of Pathologic Tumor Response and Nodal Status on Survival in the Medical Research Council Adjuvant Gastric Infusional Chemotherapy Trial. J Clin Oncol. 2016 Aug 10;34(23):2721-7. doi: 10.1200/JCO.2015.65.7692. Epub 2016 Jun 13.

  PMID: 27298411 BACKGROUND

• Lee J, Lim DH, Kim S, Park SH, Park JO, Park YS, Lim HY, Choi MG, Sohn TS, Noh JH, Bae JM, Ahn YC, Sohn I, Jung SH, Park CK, Kim KM, Kang WK. Phase III trial comparing capecitabine plus cisplatin versus capecitabine plus cisplatin with concurrent capecitabine radiotherapy in completely resected gastric cancer with D2 lymph node dissection: the ARTIST trial. J Clin Oncol. 2012 Jan 20;30(3):268-73. doi: 10.1200/JCO.2011.39.1953. Epub 2011 Dec 19.

  PMID: 22184384 BACKGROUND

• Park SH, Sohn TS, Lee J, Lim DH, Hong ME, Kim KM, Sohn I, Jung SH, Choi MG, Lee JH, Bae JM, Kim S, Kim ST, Park JO, Park YS, Lim HY, Kang WK. Phase III Trial to Compare Adjuvant Chemotherapy With Capecitabine and Cisplatin Versus Concurrent Chemoradiotherapy in Gastric Cancer: Final Report of the Adjuvant Chemoradiotherapy in Stomach Tumors Trial, Including Survival and Subset Analyses. J Clin Oncol. 2015 Oct 1;33(28):3130-6. doi: 10.1200/JCO.2014.58.3930. Epub 2015 Jan 5.

  PMID: 25559811 BACKGROUND

MeSH Terms

Conditions

Gastrointestinal Neoplasms

Interventions

Oxaliplatin; Capecitabine; Leucovorin; Fluorouracil; Radiation

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Physical Phenomena

Results Point of Contact

• Title: Eunji Jo
• Organization: Baylor College of Medicine

ejo@bcm.edu

713-798-4923

Study Officials

• Tannaz Armaghany, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine - Hematology and Oncology

Study Record Dates

• First Submitted: April 24, 2018
• First Posted: May 4, 2018
• Study Start: June 22, 2018
• Primary Completion: March 17, 2020
• Study Completion: June 18, 2020
• Last Updated: October 12, 2020
• Results First Posted: October 12, 2020

Record last verified: 2020-10

Locations

US (4)