Lag-3 and Gemcitabine for Treatment of Advanced Pancreas Cancer

NCT00732082 | Terminated Phase 1

• 1 other identifier: 07-0265
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

The overall purpose of this research is to evaluate the safety and toxicity of an investigational medication, IMP321, in patients being treated with gemcitabine. IMP321 is a synthetic protein (made in the laboratory to simulate a protein that your body makes on its own) and was designed to stimulate the immune system with the overall objective of improving the body's capacity to react to your pancreas cancer.

Conditions

Pancreatic Neoplasms

Keywords

LAG-3 and gemcitabine treatment for advanced pancreas cancer

Outcome Measures

Primary Outcomes (2)

• To evaluate the safety and tolerability of repeated IMP321 subcutaneous injections in patients being treated with gemcitabine for advanced pancreas cancer.

  6 months

• To determine the dose limiting toxicities of IMP321 in patients being treated with gemcitabine for advanced pancreas cancer.

  6 months

Secondary Outcomes (3)

• To describe the pharmacokinetics of the last IMP321 subcutaneous injection compared to the first one, in a limited number of patients.

  Pre-dose, 2 hours, 4 hours, 8 hours, 24 hours, 72 hours, and 96 hours after IMP321 administration

• To determine the pharmacodynamics of IMP321 therapy

  6 months

• To evaluate the clinical response and time to disease progression with computed tomography examinations at two month intervals (current standard of care in gemcitabine-treated patients).

  survival

Study Arms (5)

Dose Level 0

ACTIVE COMPARATOR

Gemcitabine (1 mg/m2 over 30 min) will be given on days 1, 8, and 15 of a 28 day cycle.

Drug: Gemcitabine

Dose Level 1

EXPERIMENTAL

Gemcitabine (1 mg/m2 over 30 min) will be given on days 1, 8, and 15 of a 28 day cycle. IMP321 3 mg SQ anterior surface of either the right or left thigh on Day 2. The subsequent doses will be given by subcutaneous injection on the contralateral thigh. Each single injection will be separated by a 13-day administration free period.

Drug: Gemcitabine; Biological: LAG-3

Dose Level 2

EXPERIMENTAL

Gemcitabine (1 mg/m2 over 30 min) will be given on days 1, 8, and 15 of a 28 day cycle. IMP321 6.5 mg SQ anterior surface of either the right or left thigh on Day 2. The subsequent doses will be given by subcutaneous injection on the contralateral thigh. Each single injection will be separated by a 13-day administration free perio

Drug: Gemcitabine; Biological: LAG-3

Dose Level 3

EXPERIMENTAL

Gemcitabine (1 mg/m2 over 30 min) will be given on days 1, 8, and 15 of a 28 day cycle. IMP321 13 mg SQ anterior surface of either the right or left thigh on Day 2. The subsequent doses will be given by subcutaneous injection on the contralateral thigh. Each single injection will be separated by a 13-day administration free perio

Drug: Gemcitabine; Biological: LAG-3

Dose Level 4

EXPERIMENTAL

Gemcitabine (1 mg/m2 over 30 min) will be given on days 1, 8, and 15 of a 28 day cycle. IMP321 26 mg SQ anterior surface of either the right or left thigh on Day 2. The subsequent doses will be given by subcutaneous injection on the contralateral thigh. Each single injection will be separated by a 13-day administration free perio

Drug: Gemcitabine; Biological: LAG-3

Interventions

Gemcitabine DRUG

Also known as: Gemzar

Dose Level 0; Dose Level 1; Dose Level 2; Dose Level 3; Dose Level 4

LAG-3 BIOLOGICAL

Dose Level 1; Dose Level 2; Dose Level 3; Dose Level 4

Eligibility Criteria

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

You may qualify if:

• Patient must have a newly diagnosed, histologically or cytologically confirmed diagnosis of pancreatic adenocarcinoma (primary tumor or metastasis). The histological slides or blocks must be available for review.
• Patient must have advanced disease (characterized by metastasis or locally advanced disease), or unable to undergo surgical treatment due to extent of disease or pre-existing health conditions precluding surgical treatment.
• Measurable or evaluable disease: RECIST Criteria will be used to assess and survey extent of disease
• Patients must be ≥ 18 years old.
• Performance Status: Karnofsky Performance Status (KPS) ≥ 70
• Life Expectancy \> 12 weeks.
• No previous history of chemotherapy for pancreas cancer in the metastatic setting prior to the start of protocol treatment.
• Patients must have recovered from uncontrolled, intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris or cardiac arrhythmia.
• Patients must have adequate bone marrow function defined as an absolute neutrophil count \>1,500/mm3, platelet count \>100,000/mm3 and hemoglobin \>10 g/dl.
• Patients must have adequate renal function defined as serum creatinine ≤ 2.0 mg/dl or creatinine clearance ≥ 60 ml/min/1.73m2 for patients with creatinine levels above 2.0 mg/dl.
• Patients must have adequate hepatic function with total bilirubin ≤ 1.5 times the institutional normal value and AST ≤ 2 times the institutional normal value.
• Patient must have no prior or current active autoimmune disease requiring management with immunosuppression. This includes inflammatory bowel disease, systemic vasculitis, scleroderma, psoriasis, hemolytic anemia, immune-mediated thrombocytopenia, rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome, sarcoidosis or other rheumatologic disease. Asthma and chronic obstructive pulmonary disease that does not require daily systemic corticosteroids is acceptable.
• The patient with previous history of malignancy is eligible for this study only if the patient meets the following criteria for cancer survivor:
• (i) patient has undergone potentially curative therapy for all prior malignancies;
• (ii) patient has been considered disease free for at least 5 years.

You may not qualify if:

• Patient is currently receiving other investigational agents.
• Pregnant and nursing women patients are not eligible.
• Patients known to be HIV (patient self-report) positive are ineligible because of the potential inability to modulate immune responses.
• Patients with a QTc of \>460 msec.

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University

St Louis, Missouri, 63110, United States

Location

Related Publications (28)

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Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Gemcitabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• William G. Hawkins, M.D.

  Washington Univerisity

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2008
• First Posted: August 11, 2008
• Study Start: February 1, 2009
• Primary Completion: February 1, 2010
• Study Completion: September 1, 2012
• Last Updated: June 12, 2013

Record last verified: 2013-06

Locations

US (1)