Clinical trial NCT03110926: Induction Chemotherapy for Locally Advanced Esophageal Cancer
Official title: Induction Chemotherapy for Locally Advanced Esophageal Cancer: A Phase II Study
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Esophageal Carcinoma
Lead sponsor: University of Rochester
Sponsor class: OTHER
First posted: 2017-04-12
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: Evaluate mFOLFOX6 (5-Fluorouracil, Leucovorin and Oxaliplatin) chemotherapy as induction treatment prior to standard neoadjuvant chemoradiation to decrease the rate of distant recurrence among patients with locally advanced esophageal cancer.

Detailed description: The goal of the study is to evaluate mFOLFOX6 (5-Fluorouracil, Leucovorin and Oxaliplatin) chemotherapy as induction treatment prior to standard neoadjuvant chemoradiation to decrease the rate of distant recurrence among patients with locally advanced esophageal cancer. mFOLFOX6 is frequently used to treat metastatic esophageal cancer because of its high response rate in this setting. It has shown promising efficacy in several trials of patients with advanced esophageal cancer and it is the most commonly used combination regimen for this group of patients in the United States.

The investigators propose treating a sample of 40 patients with 3 cycles of induction mFOLFOX6 chemotherapy over six weeks followed by standard chemoradiation and surgery. The investigators hypothesize that patients who undergo induction chemotherapy with mFOLFOX6 prior to standard neoadjuvant chemoradiation and surgery will have a lower rate of distant disease recurrence compared to standard neoadjuvant chemoradiation and surgery.

Eligibility criteria: Inclusion Criteria:

1. Must have histologically proven adenocarcinoma, squamous cell carcinoma or undifferentiated carcinoma of the esophagus, GE junction and/or gastric cardia.
2. Must have potentially resectable disease.
3. Must have ECOG performance status 0 or 1.
4. Must have adequate organ function as defined by the following criteria:

   * ANC ≥ 1,500/mm3
   * Platelet count ≥ 100,000/mm3
   * Creatinine (Cr) ≤ 1.5 mg and/or creatinine clearance ≥ 60cc/min.
   * Total bilirubin must be ≤ 1.5 x ULN unless the patient has a chronic grade 1 bilirubin elevation due to Gilbert's disease or similar syndrome due to slow conjugation of bilirubin.
   * Alkaline phosphatase must be ≤ 2 x ULN.
   * AST \& ALT must be ≤ 3 x ULN.
5. Men and women of reproductive potential must agree to use an effective contraception method
6. Must be willing and able to provide written informed consent
7. Must be ≥ 18 years or older

Exclusion Criteria:

1. Prior chemotherapy, thoracic radiotherapy or prior surgical resection for an esophageal tumor.
2. Known distant metastases.
3. Patients with prior malignancies are eligible if they have been disease-free for \> 5 years and are deemed by their physician to be at low risk for recurrence. Patients with squamous or basal cell carcinoma of the skin, melanoma in situ, carcinoma in situ of the cervix, or carcinoma in situ of the colon or rectum that have been effectively treated are eligible, even if these conditions were diagnosed within 5 years prior to randomization.
4. Known ≥ grade 2 neuropathy.
5. Known non-malignant systemic disease (cardiovascular, renal, hepatic, etc.) that would preclude any of the study therapy drugs.
6. Known psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude them from meeting the study requirements.
7. Women who are pregnant or nursing.
8. Women and men of reproductive potential who are expecting to conceive or father children.

Primary outcomes:
measure: Disease-free survival rate
timeFrame: 2 years
Secondary outcomes:
measure: Pathologic examination
timeFrame: 2 years
measure: Toxicities as Assessed by CTCAE v4.0
timeFrame: 25-29 weeks
measure: Overall survival
timeFrame: 2 years
measure: Overall disease-free survival
timeFrame: 2 years
Other outcomes:
Locations:
city: Rochester
country: United States
facility: University of Rochester
state: New York
Study officials:
affiliation: University of Rochester Wilmot Cancer Center
name: Richard Dunne, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Shapiro J, van Lanschot JJB, Hulshof MCCM, van Hagen P, van Berge Henegouwen MI, Wijnhoven BPL, van Laarhoven HWM, Nieuwenhuijzen GAP, Hospers GAP, Bonenkamp JJ, Cuesta MA, Blaisse RJB, Busch ORC, Ten Kate FJW, Creemers GM, Punt CJA, Plukker JTM, Verheul HMW, Bilgen EJS, van Dekken H, van der Sangen MJC, Rozema T, Biermann K, Beukema JC, Piet AHM, van Rij CM, Reinders JG, Tilanus HW, Steyerberg EW, van der Gaast A; CROSS study group. Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol. 2015 Sep;16(9):1090-1098. doi: 10.1016/S1470-2045(15)00040-6. Epub 2015 Aug 5.
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