FOLFOX-6 Induction Chemotherapy Followed by Esophagectomy and Post-operative Chemoradiotherapy in Patients With Esophageal Adenocarcinoma

NCT02037048 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: CASE6213
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well oxaliplatin, leucovorin calcium, and fluorouracil followed by surgery and response based concurrent chemotherapy and radiation therapy works in treating patients with cancer of the esophagus, gastroesophageal junction, or gastric cardia. Drugs used in chemotherapy, such as oxaliplatin, leucovorin calcium, fluorouracil, paclitaxel, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high energy x rays to kill tumor cells. Giving chemotherapy followed by surgery and response based chemotherapy and radiation therapy may kill more tumor cells.

Conditions

Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Adenocarcinoma of the Gastric Cardia; Stage IIIA Esophageal Cancer; Stage IIIB Esophageal Cancer; Stage IIIC Esophageal Cancer

Outcome Measures

Primary Outcomes (1)

• Recurrence Free Survival (RFS) compared to historical averages

  Compare the number of study patients who achieved RFS with \>50% remaining viable tumor after response adapted adjuvant chemoradiotherapy to historical data among patients with \>50% viable tumor after induction chemotherapy. A once sided test (p\<=0.05) will be used to describe significance of change.

  1 year

Secondary Outcomes (9)

• Symptomatic response

  Up to 5 years

• Endoscopic response

  Up to 5 years

• Pathologic response

  Up to 5 years

• Complete resection (R0) rate

  Up to 5 years

• Incidence of toxicity

  Up to 5 years

Other Outcomes (4)

• Change in circulating tumor cells (CTCs)

  Baseline to up to 2 months

• Change in Ki-67 expression

  Baseline to up to 2 months

• HER2 overexpression

  Up to 5 years

Study Arms (2)

Positive Pathologic Response

ACTIVE COMPARATOR

Patients with ≤50% viable tumor cells remaining in the surgical specimen will receive postoperative chemo-radiotherapy with the mFOLFOX6 regimen

Drug: oxaliplatin; Drug: leucovorin calcium; Drug: fluorouracil; Procedure: therapeutic conventional surgery; Radiation: radiation therapy

Negative Pathologic Response

EXPERIMENTAL

Patients with \>50% viable tumor cells remaining in the surgical specimen, will receive postoperative chemo-radiotherapy with weekly carboplatin and paclitaxel.

Drug: oxaliplatin; Drug: leucovorin calcium; Drug: fluorouracil; Procedure: therapeutic conventional surgery; Radiation: radiation therapy; Drug: carboplatin; Drug: paclitaxel

Interventions

oxaliplatin DRUG

Given IV

Also known as: 1-OHP, Dacotin, Dacplat, Eloxatin, L-OHP

Negative Pathologic Response; Positive Pathologic Response

leucovorin calcium DRUG

Given IV

Also known as: CF, CFR, LV

Negative Pathologic Response; Positive Pathologic Response

fluorouracil DRUG

Given IV

Also known as: 5-fluorouracil, 5-Fluracil, 5-FU

Negative Pathologic Response; Positive Pathologic Response

therapeutic conventional surgery PROCEDURE

Undergo therapeutic conventional surgery

Negative Pathologic Response; Positive Pathologic Response

radiation therapy RADIATION

Undergo radiation therapy

Also known as: irradiation, radiotherapy, therapy, radiation

Negative Pathologic Response; Positive Pathologic Response

carboplatin DRUG

Given IV

Also known as: Carboplat, CBDCA, JM-8, Paraplat, Paraplatin

Negative Pathologic Response

paclitaxel DRUG

Given IV

Also known as: Anzatax, Asotax, TAX, Taxol

Negative Pathologic Response

Eligibility Criteria

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

You may qualify if:

• Patients must have a histologic diagnosis of adenocarcinoma of the esophagus, GEJ, or GC based on biopsy material or adequate cytologic exam; tumors of the GC are defined as originating within 5 cm of the GEJ
• Patients must be clinically staged according to the 7th edition (2010) of the American Joint Committee on Cancer (AJCC) staging system and must have either clinical T3-4a, or ≥ N1 disease; staging should include upper endoscopy with endoscopic ultrasound and a fludeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) scan (with diagnostic CT abdomen/pelvis preferred)
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Absolute neutrophil count ≥ 1,500/ul
• Platelet count ≥100,000/ul
• Serum creatinine (Scr) ≤ 1.5mg/dl; if the Scr \> 1.5, patients may still be eligible if the calculated glomerular filtration rate (GFR) (Cockroft-Gault) is ≥ 40ml/minute
• Serum total bilirubin ≤ 1.5X the institutional upper limit of normal (ULN)
• Alkaline phosphatase ≤ 3X the institutional ULN
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 3X the institutional ULN
• Patients with Gilbert's syndrome are eligible provided the total bilirubin is ≤ 3 and the remainder of the liver function tests (ALT, AST, alkaline phosphatase \[ALK Phos\]) are within the institutional normal range
• Patients must have a forced expiratory volume in one second (FEV-1) and diffusing capacity of the lung for carbon monoxide (DLCO) \> 50% predicted
• Patients or their legal representatives must be able to read, understand, provide and sign informed consent to participate in the trial
• Patients of childbearing potential must agree to use an effective form of contraception during this study and for 90 days following the last dose of chemotherapy; an effective form of contraception is an oral contraceptive or a double barrier method

You may not qualify if:

• Patients with any other diagnosis except for adenocarcinoma (squamous cell carcinoma, small cell carcinoma, mixed adenosquamous, lymphoma, sarcoma, etc.) will be ineligible
• Patients with evidence of clinical T4b (unresectable) or M1 (distant metastasis) according to the AJCC 2010 staging system will be ineligible
• No prior chemotherapy, radiation therapy, or surgery for this malignancy will be allowed; prior endoscopic procedures for superficial disease (endoscopic mucosal resection, cryotherapy, photodynamic therapy, etc.) will not exclude a patient; prior dilatation is also allowed
• Patients with another active malignancy will not be eligible except for:
• Resected basal cell carcinoma and squamous cell carcinoma of the skin, cervical or prostatic intraepithelial neoplasia, and ductal or lobular carcinoma in situ of the breast
• Patients with localized prostate cancer who have received curative intent therapy are also eligible provided:
• Surgically treated patients have an undetectable prostate specific antigen (PSA)
• Patients treated with brachytherapy have a PSA within the institutional normal range
• Patients who have received pelvic external beam radiotherapy are not eligible
• Patients with a clinically apparent active infection will not be eligible (please note, an isolated elevation in the white blood cell count, by itself, does not constitute evidence of an infection)
• Patients with known hypersensitivity to any component of the chemotherapy regimen will not be eligible
• Patients with a baseline peripheral neuropathy ≥ grade 2 will not be eligible
• Patients who are receiving any other concurrent investigational therapy, or who have received investigational therapy within 30 days of the first scheduled day of protocol treatment (investigational therapy as defined as treatment for which there is currently no regulatory authority approved indication) will not be eligible
• Patients who are pregnant or lactating will not be eligible; pregnant patients are ineligible
• Patients with angina, a cardiac ejection fraction \< 50%, or ischemic heart disease are not eligible

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead

Study Sites (1)

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106-5065, United States

Location

MeSH Terms

Conditions

Adenocarcinoma Of Esophagus; Esophageal Neoplasms

Interventions

Oxaliplatin; Leucovorin; Fluorouracil; Radiotherapy; Radiation; Carboplatin; Paclitaxel; Taxes

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Therapeutics; Physical Phenomena; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations

Study Officials

• Michael McNamara, MD

  Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2014
• First Posted: January 15, 2014
• Study Start: February 10, 2014
• Primary Completion: March 18, 2022
• Study Completion: October 1, 2025
• Last Updated: January 8, 2024

Record last verified: 2024-01

Locations

US (1)