Phase 2 Study of Erlotinib, Gemcitabine and Oxaliplatin Combination Chemotherapy to Advanced Pancreatic Cancer (GEMOX-T)

Phase 2 Study of GEMOX-T in Previously Untreated Patients With Advanced Pancreatic Cancer

Erlotinib is an orally available, reversible tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR). Association of chemoresistance with the activity of certain tyrosine kinases (e.g. ErbB-1 and Src) has been described for pancreatic cancer and makes a strong case for combining gemcitabine with tyrosine kinase inhibitors. In a phase III trial, the addition of erlotinib to gemcitabine improved survival compared with gemcitabine alone in advanced pancreatic cancer (MJ Moor et al). Also, gemcitabine in combination with oxaliplatin is superior to gemcitabine alone in terms of progression free survival and response rate in one phase III trial (Louvet et al). Taken together, combining erlotinib with gemcitabine and oxaliplatin may further improve the overall survival and clinical benefit of advanced pancreatic cancer.

Study Overview

• Status: Completed
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: Erlotinib; Drug: Gemcitabine; Drug: Oxaliplatin

Detailed Description

Open, uncontrolled, multicenter, phase II study

This study will enroll previous chemo-naïve patients with locally advanced unresectable or metastatic pancreatic cancer.

Study regimen:

• Erlotinib 100 mg po qd daily AND
• Gemcitabine 1000 mg/m² with 150mL of normal saline intravenously infusion over 100min on Day 1
• Oxaliplatin 100 mg/m2 with 500mL of 5DW intravenously a 2-hour infusion on D2 Every 2 weeks

Each two weeks is a cycle. If at end of 12 cycles response continues, will administer Gemcitabine and erlotinib until progression.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Gyeonggi
    • Bucheon, Gyeonggi, Korea, Republic of, 420-767
      • Soonchunhyang University Bucheon Hospital

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. Age over 18 years
2. ECOG performance status of ≤2
3. Histologically confirmed adenocarcinoma of the pancreas
4. The disease is Locally advanced deemed by the surgeon to be unresectable, or metastatic disease.
5. Prior chemotherapy is not permitted, except for fluorouracil given concurrently as a radiosensitizer.

6. Patients must have normal organ function evidenced by

   • Number of absolute neutrophil counts (ANC) > 1.5 x 109/L
   • Number of thrombocytes > 100 x 109/L
   • Total bilirubin < 1.5 x upper limit of normal (although patients with a Total bilirubin count between 1.5 and 3 x upper limit of normal in whom a decrease is anticipated, ex. Biliary stent insertion)ALAT, ASAT < 3 x upper limit of normal (in case of liver metastasis, 5 x upper limit of normal)
   • Alkaline phosphatase < 3 x upper limit of normal (in case of liver metastasis, 5 x upper limit of normal)
7. Pain should be controlled for at least two weeks without an increase in the narcotic consumption.
8. Biliary obstruction should be controlled for at least two weeks evident by stable or improving liver function tests especially total bilirubin.
9. Patient has signed a Patient Informed Consent Form.
10. For all females of childbearing potential, a negative pregnancy test must be obtained within 72 hours before starting therapy.
11. Is able to take medications orally
12. A patient with at least one measurable primary lesion of which the diameter is confirmed to be 10mm in spiral CT or multidetector CT (MD CT) or 20 mm or longer in conventional CT (it should be used by a consistent method during the study period)

Exclusion Criteria:

1. Tumor type other than adenocarcinoma
2. Evidence of uncontrolled CNS disease (patients with controlled CNS disease for 4 weeks using the same imaging method and for whom are off steroid will be eligible)
3. Uncontrolled Nausea and Vomiting
4. Diagnosis of other malignancy in the last 5 years excluding non-melanoma skin cancer and in -situ cervical cancer.
5. Subjects unlikely to comply with protocol, e.g. uncooperative attitude, inability to return for follow- up visits and unlikelihood of completing the study.
6. Any known history of hypersensitivity to the study drugs.
7. Pregnant or lactating women.
8. Symptomatic peripheral sensory neuropathy (NCI CTCAE v3.0 ≥ grade 2)
9. Other serious illness or medical condition, notably heart or lung failure, active uncontrolled infection
10. Prior radiotherapy was administered to target lesions selected for this study, or radiotherapy to the non-target lesions has been completed within 4 weeks before being included in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Tarceva, Gemcitabine, Oxaliplatin; Erlotinib 100 mg po qd daily AND; Gemcitabine 1000 mg/m² with 150mL of normal saline intravenously infusion over 100min on Day 1; Oxaliplatin 100 mg/m2 with 500mL of 5DW intravenously a 2-hour infusion on D2 Every 2 weeks Each two weeks is a cycle. If at end of 12 cycles response continues, will administer Gemcitabine and erlotinib until progression.

Drug: Erlotinib; Erlotinib 100 mg po qd daily; Other Names: tarceva; Drug: Gemcitabine; Gemcitabine 1000 mg/m² with 150mL of normal saline intravenously infusion over 100min on Day 1; Other Names: gemza; gemcibine; Drug: Oxaliplatin; Oxaliplatin 100 mg/m2 with 500mL of 5DW intravenously a 2-hour infusion on D2; Other Names: oxalitin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate	Responses are assessed every 2 cycles according to RECIST; the imaging tests are performed in a week preceding the corresponding cycles, and can also be repeated at any other time if clinically indicated, for example, to confirm disease progression. At any time, patients with progressive disease are withdrawn.	24 months (01/2011 and end of study 01/2013)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival		1 year
disease control rate(SD,PR,CR)	Responses are assessed every 2 cycles according to RECIST; the imaging tests are performed in a week preceding the corresponding cycles, and can also be repeated at any other time if clinically indicated, for example, to confirm disease progression. At any time, patients with progressive disease are withdrawn.	24 months (01/2011 and end of study 01/2013)

Collaborators and Investigators

• Sponsor: Soonchunhyang University Hospital
• Investigators: Study Director: Kyu Taek Lee, Dr, Soonchunhyang University Hospital; Study Director: Hee Sook Park, Dr, Soonchunhyang University Hospital; Study Director: Dae Sik Hong, Dr, Soonchunhyang University Hospital

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): March 1, 2014

Study Registration Dates

• First Submitted: January 2, 2012
• First Submitted That Met QC Criteria: January 5, 2012
• First Posted (Estimate): January 6, 2012

Study Record Updates

• Last Update Posted (Estimate): April 3, 2014
• Last Update Submitted That Met QC Criteria: April 2, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: advanced unresectable or metastatic Pancreatic Cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protein Kinase Inhibitors; Gemcitabine; Erlotinib Hydrochloride; Oxaliplatin
• Other Study ID Numbers: Yun-11349