Antigen-specific Cancer Immunotherapy (TG01) and Gemcitabine as Adjuvant Therapy in Resected Pancreatic Cancer

Study Overview
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Brief Summary
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The purpose of this study is to investigate the effect of TG01 and Granulocyte macrophage colony stimulating factor (GM-CSF) when given in addition to gemcitabine (chemotherapy) and Understand any possible side effects of the additional use of TG01/GM-CSF with gemcitabine Investigate whether TG01/GM-CSF when given with gemcitabine can produce an immune response Investigate if the treatment can delay or reduce recurrence of the disease

Official Title
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A Phase I/II Trial of TG01 and Gemcitabine as Adjuvant Therapy for Treating Patients With Resected Adenocarcinoma of the Pancreas

Conditions
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Pancreatic Cancer, Resected

Intervention / Treatment
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* Biological: TG01
* Biological: TG01


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed diagnosis of adenocarcinoma of the pancreas Stage I or II disease (clinical stage T1-3, N0-1, M0 by AJCC staging criteria). Successful surgical resection Complete resection (R0) or with microscopic residual disease (R1) Expected to receive gemcitabine monotherapy as adjuvant chemotherapy Laboratory Values: Absolute neutrophil count ≥ 1.5 x 10^9/l Platelets ≥100 x 10^9/l Haemoglobin ≥ 9 g/dl Total bilirubin ≤ 1.5 x UNL Serum creatinine ≤ 1.5 x UNL Albumin ≥ 2.5 g/dl AST or ALT ≥ 5 x UNL 18 years of age or older. ECOG performance status (PS) of 0-1. Life expectancy of at least 6 months Men and women of childbearing potential must be willing to use effective methods of contraception to prevent pregnancy Provide written (signed) informed consent to participate in the trial prior to any trial specific screening procedures Exclusion Criteria: Has received an investigational drug within 4 weeks prior to Trial drug administration Has received previous therapy for pancreatic cancer including radiation or chemotherapy (except for the primary resection or primary neoadjuvant chemotherapy). Is currently receiving any agent with a known effect on the immune system, unless at dose levels that are not immunosuppressive (e.g. Prednisone at 10 mg/day or less or as inhaled steroid at doses used for the treatment of asthma). Has any other serious illnesses or medical conditions such as, but not limited to: Any uncontrolled infection Uncontrolled cardiac failure classification III or IV (NY Heart Association) Uncontrolled systemic and gastro-intestinal inflammatory conditions Bone marrow dysplasia History of auto-immune disease History of adverse reactions to vaccines Known history of positive tests for HIV/AIDS, hepatitis B or C Pregnant or lactating females or have no pregnancy test at baseline (postmenopausal women must have been amenorrhoeic for at least 12 months to be considered of non-childbearing potential). Contraindication to gemcitabine treatment Have had any other malignancies within last 3 years (except for adequately treated carcinoma of the cervix or basal or squamous cell skin cancer) Known malignant brain lesion(s) Are unlikely to start chemotherapy within 12 weeks of surgery (e.g. delayed wound healing, or infection, etc.) Are not expected to complete 6 cycles of chemotherapy Are planned to receive yellow fever or other live (attenuated) vaccines during the course of study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TG01/GM-CSF and Gemcitabine<br> | Biological: TG01<br>* TG01 and GM-CSF will be administered on days 1, 8, 15, 22 and 36. TG01 alone will also be given on days 36 and 50 for DTH assessment. Gemcitabine will start at least 3 weeks after TG01/GM-CSF and will be given on days 1, 8 and 15 of a four-weeks cycle up to 6 cycles in total. Once chemotherapy is completed, GM-CSF and TG01 injections will resume and will be given every 4 weeks from the end of the chemotherapy period up to week 52 (plus once at week 5 post-chemotherapy) and then every 12 weeks from week 52 to week 104. TG01 alone will be given 8 weeks after the end of chemotherapy for DTH assessment. TG01 will be given at a dose of 0.70 mg/injection and GM-CSF will be given at a dose of 30 micrograms both as intradermal injections. Gemcitabine will be given at a dose of 1000 mg/m2 iv over 30 minutes<br>Biological: TG01<br>* For patients not able to start TG01 quickly after surgery, the vaccination can start at the same time as the chemotherapy as long as they start within 12 weeks from surgery. Gemcitabine will start at the same time as TG01/GM-CSF and will be given on days 1, 8 and 15 of a four-weeks cycle up to 6 cycles in total. TG01 will be given at a dose of 0.70 mg/injection and GM-CSF will be given at a dose of 30 micrograms both as intradermal injections. Gemcitabine will be given at a dose of 1000 mg/m2 iv over 30 minutes<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patients' Safety During Study | Assess the safety (number and nature of Adverse events and laboratory data occurring during study (before, during and after chemotherapy is given) in subjects treated with the Pancreatic Cancer ASCI | 2 years | 
| Patients' Immune Response | Assess the Immune response (DTH responses and Proliferative T-cell responses) up to 2 years of treatment | During the 2 years of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Efficacy | Efficacy exploring disease free survival and overall survival. | DFS was followed for up to 2 years and OS until last patient included had been in the study for 3 years. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pancreatic cancer, resected, Vaccine, KRAS