Docetaxel-polymeric Micelles(PM) and Oxaliplatin for Esophageal Carcinoma (DOSE)

A Phase II Trial of Docetaxel-polymeric Micelles(PM) Plus Oxaliplatin as a First-line Chemotherapy in Patients With Esophageal Squamous Cell Carcinoma

Esophageal or esophageal-gastric junction squamous cell cancer has dismal prognosis. And still no promising chemotherapeutic drugs is existed. In this study, The investigators wanted to look at the effects and safety of first line docetaxel-PM and oxaliplatin weekly administration chemotherapy for the participants with inoperable or metastatic esophageal squamous cell carcinoma.

Study Overview

• Status: Unknown
• Conditions: Metastatic Cancer; Esophagus Squamous Cell Carcinoma (SCC)
• Intervention / Treatment: Drug: Docetaxel-PM; Drug: Oxaliplatin

Detailed Description

Few results directly study the combination of docetaxel and oxaliplatin in the squamous cell cancer of the esophagus, but some studies have shown that it is safe to In the phase II study for the patients with gastroesophageal junction adenocarcinoma, a prior study reported the efficacy and safety of the combination therapy of docetaxel 80mg/m2 and oxaliplatin 100mg/m2 every 3 weeks schedule. Entire response rate was 34% and median survival duration was 11.6 months. Over grades 3 anemia and neutropenia were found in 17%, respectively, and non-hematological toxicities were mostly mild to moderate. In this study, a five-day preventive granulocyte colony-stimulating factor (G-CSF) was used to reduce hematology toxicity.

Meanwhile, there was the phase I/II studies of added capecitabine to docetaxel and oxaliplatin with divided schedule d1 and d8 every 3weeks for reducing toxicities. The subjects who participated in this study had at least one previous history of chemotherapy, but overall response rates were 43% and median values for the entire duration of survival were 9.8months. However, the side effects were significant, with 30 % of patients seeing diarrhea of Grade 3 or higher and 17 % seeing infection of Grade 3 or higher (SAE) reported at 37 %.

Looking at the reasons and background for this, the effects of docetaxel on esophageal squamous cell cancer patients are already known, and weekly divided administration has also demonstrated a reasonable level of effectiveness and safety. In studies conducted on gastric and esophageal adenocarcinoma, the combination of docetaxel and oxaliplatin also showed reasonable levels of effects and side effects.

In this study, The investigators wanted to look at the effects and safety of first line docetaxel-PM and oxaliplatin weekly administration chemotherapy for the participants with inoperable or metastatic esophageal squamous cell carcinoma.

• Study Type: Interventional
• Enrollment (Anticipated): 38
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sung Yong Oh, MD; Phone Number: +82512402808; Email: drosy@dau.ac.kr

Study Locations

• Korea, Republic of
  • Busan, Korea, Republic of, 49201
    • Recruiting
    • Dong-A University Hospital
    • Contact: Sung Yong Oh, MD; Phone Number: +82512402808; Email: drosy@dau.ac.kr
    • Contact: EunKyung Lee, RN; Phone Number: +82512405044; Email: dongahicrc12@naver.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. A patient whose squamous cell cancer of the esophagus or esophago-gastric junction has been confirmed by biopsy or cytology.
2. A patient who is not subject to local treatment such as surgical excision or concurrent definitive chemoradiotherapy.
3. Metastatic or relapsed esophageal cancer patients who planned first line palliative treatment.
4. Patients' age over 18
5. Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0-2
6. Patient has measurable lesions with RECIST v1.1

7. Patients with appropriate organ functions, such as the following, within seven days prior to the start of a clinical trial

   • Proper bone marrow function (ANC ≥ 1500/uL, Platelets ≥ 100,000/uL and Hb 8/microliter(uL))
   • Proper kidney function (serum creatinine ≤ 1.5 mg/L, 24-hour urine test or creatinine clearance ≥ 60 ml/min based on Cockcroft-Gault formula)
   • Appropriate liver function (bilirubin ≤ 1.5 mg/dL, transaminases aspartate transaminase (AST or SGOT) and alanine transaminase (AST or SGOT) ≤ 2.5 times normal upper limit)
8. Patients with at least three months of an expected life.
9. Signing written consent from patients or their legal guardians and understanding the right to withdraw consent at any time without disadvantage.

Exclusion Criteria:

1. In the case that the following treatment has been received in the past for the local stage treatment more than 6 months from the end of the treatment, enrolment is allowed.

   • Neoadjuvant chemotherapy
   • Concurrent or sequential chemoradiotherapy
   • Adjuvant chemotherapy
   • Adjuvant concurrent or sequential chemoradiotherapy
   • Definitive concurrent or sequential chemoradiotherapy
2. Patients with a history of administration of docetaxel, paclitaxel, or oxaliplatin at any time in the past.
3. Patients who have been treated for other active cancers other than esophageal cancer less than five years (but cured kin basal cell cancer or cured cervical carcinoma in situ are excluded).
4. The clinically confirmed esophagus obstruction, gastrointestinal bleeding, or perforation (except if the symptoms are sufficiently controlled through proper procedures such as stents).
5. Patients with significant, uncontrolled cardiovascular disease, infection, or infectious fever.
6. Patients with uncontrolled brain metastasis.
7. In the case of major surgery within the first two weeks of clinical trial treatment, the patient must recover sufficiently from the effects of this surgery.
8. Patients with pregnancy, breast feeding, or future plans.
9. Because of uncontrolled diabetes or diabetic neuropathy, patients who have any subjective symptoms regardless of their degree
10. Patients who have taken antihistamine or steroid within four weeks of clinical trial treatment
11. In combination with the state of Docetaxel-PM, patients who are not permitted to take combined medication (patients with severe renal dysfunction, para-platin, platinum compound, patients who have hypersensitivity to mannitol, etc.)
12. Patients with hypersensitivity history of Polysorbate 80
13. A patient who has hypersensitivity history to Docetaxel-PM or oxaliplatin or any drug containing platinum.
14. Patients with peripheral sensory neuropathy with functional impairment (may aggravate peripheral neuropathy) prior to clinical trial

15. Other cases

    • Have experienced an infection or other serious medical problems that could cause damage to a patient's functions, making it difficult for the patient to receive treatment in a research plan.
    • Mental, neurological, or dementia that can prevent a person from understanding and submitting a written statement and consent form
    • Patients who are certain to be out of the clinical trial or who cannot be monitored regularly for the following reasons: For example, psychological, social, family or geographical reasons, or conditions that make it difficult to observe or comply with appropriate clinical trial plans.
    • Uncontrolled hepatitis and chronic liver disease
    • Other patients who are judged unfit for clinical trials by their physicians and researchers

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Docetaxel-PM+Oxaliplatin; Docetaxel-PM 35mg/m2 D1, 8 I.V.; Oxaliplatin 120mg/m2 D1 I.V. Every 3 weeks till progression	Drug: Docetaxel-PM; Docetaxel-PM 35mg/m2 intravenous over 1hour day1 and 8 every 3 weeks till progression; Other Names: NANOXEL-M; Drug: Oxaliplatin; Oxaliplatin 120mg/m2 intravenous over 2 hour day 1 every 3 weeks till progression; Other Names: NEXATIN

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate	complete response + partial response by RECIST	up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	progression or death	up to 12 months
Overall survival	death event	up to 12 months
Adverse event	Hypersensitivity or any side effects by NCI-Common Terminology Criteria for Adverse Events (CTCAE) v4.03	up tp 12 months

Collaborators and Investigators

• Sponsor: Sung Yong Oh

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 1, 2018
• Primary Completion (ANTICIPATED): March 30, 2020
• Study Completion (ANTICIPATED): March 30, 2021

Study Registration Dates

• First Submitted: July 1, 2018
• First Submitted That Met QC Criteria: July 1, 2018
• First Posted (ACTUAL): July 13, 2018

Study Record Updates

• Last Update Posted (ACTUAL): July 17, 2018
• Last Update Submitted That Met QC Criteria: July 13, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: esophageal cancer; inoperable; metastatic; relapsed
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Neoplasms, Squamous Cell; Esophageal Neoplasms; Carcinoma; Carcinoma, Squamous Cell; Esophageal Squamous Cell Carcinoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel; Oxaliplatin
• Other Study ID Numbers: DAUHIRB-18-041

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No