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

Study Description

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Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Pancreatic Cancer, Resected	Biological: TG01	Phase 1; Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	32 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Phase I/II Trial of TG01 and Gemcitabine as Adjuvant Therapy for Treating Patients With Resected Adenocarcinoma of the Pancreas
Study Start Date :	December 2012
Estimated Primary Completion Date :	June 2018
Estimated Study Completion Date :	June 2018

Arms and Interventions

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Arm

Intervention/treatment

Experimental: TG01/GM-CSF and Gemcitabine

Biological: TG01; 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; Biological: TG01; 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

Outcome Measures

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Primary Outcome Measures :

1. Patients' safety during study [ Time Frame: 2 years ]
   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. Patients' Immune response [ Time Frame: During the 2 years of treatment ]
   Assess the Immune response (DTH responses and Proliferative T-cell responses) up to 2 years of treatment

Secondary Outcome Measures :

1. Clinical Efficacy [ Time Frame: 2 years ]
   Efficacy exploring disease free survival and overall survival

Other Outcome Measures:

1. Relationship between (KRAS) status and clinical efficacy [ Time Frame: 2 years ]
   Relationship between KRAS status and recurrence

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 99 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

1. Histologically or cytologically confirmed diagnosis of adenocarcinoma of the pancreas
2. Stage I or II disease (clinical stage T1-3, N0-1, M0 by AJCC staging criteria).

3. Successful surgical resection

   • Complete resection (R0) or with microscopic residual disease (R1)
   • Expected to receive gemcitabine monotherapy as adjuvant chemotherapy

4. 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
5. 18 years of age or older.
6. ECOG performance status (PS) of 0-1.
7. Life expectancy of at least 6 months
8. Men and women of childbearing potential must be willing to use effective methods of contraception to prevent pregnancy
9. Provide written (signed) informed consent to participate in the trial prior to any trial specific screening procedures

Exclusion Criteria:

1. Has received an investigational drug within 4 weeks prior to Trial drug administration
2. Has received previous therapy for pancreatic cancer including radiation or chemotherapy (except for the primary resection or primary neoadjuvant chemotherapy).
3. 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).

4. 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
5. Known history of positive tests for HIV/AIDS, hepatitis B or C
6. 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).
7. Contraindication to gemcitabine treatment
8. Have had any other malignancies within last 3 years (except for adequately treated carcinoma of the cervix or basal or squamous cell skin cancer)
9. Known malignant brain lesion(s)
10. Are unlikely to start chemotherapy within 12 weeks of surgery (e.g. delayed wound healing, or infection, etc.)
11. Are not expected to complete 6 cycles of chemotherapy
12. Are planned to receive yellow fever or other live (attenuated) vaccines during the course of study

Contacts and Locations

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Locations

Norway
Oslo University Hospital HF the Norwegian Radium Hospital
Oslo, Norway
Spain
Centro Integral Oncologico Clara Campal / Hospital HM Universitario Sanchinarro
Madrid, Spain, 28050
United Kingdom
Queen Elizabeth University Hospital / Edgaston /
Birmingham, United Kingdom, B15 2TH
University of Liverpool / Molecular and Clinical Cancer Medicine
Liverpool, United Kingdom, L69 3GA
University of Manchester / The Christie NHS Foundation Trust
Manchester, United Kingdom, M20 43 X

Sponsors and Collaborators

Targovax ASA

Investigators

Principal Investigator:	Daniel PALMER	University of Liverpool Molecular and Clinical Cancer Medicine /UCD Duncan Building / Daulby Street / Liverpool
Principal Investigator:	Juan VALLE	University of Manchester / The Christie NHS Foundation Trust /Wilmslow Road / Manchester
Principal Investigator:	Svein DUELAND	Oslo University Hospital HF / the Norwegian Radium Hospital / Ullernchausseen 70 / Oslo
Principal Investigator:	Yuk Ting MA	Queen Elizabeth University Hospital / Edgaston / Birmingham
Principal Investigator:	Emiliano Calvo	Centro Integral Oncologico Clara Campal / Hospital HM Universitario Sanchinarro / Madrid

More Information

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Publications:

Gjertsen MK, Buanes T, Rosseland AR, Bakka A, Gladhaug I, Søreide O, Eriksen JA, Møller M, Baksaas I, Lothe RA, Saeterdal I, Gaudernack G. Intradermal ras peptide vaccination with granulocyte-macrophage colony-stimulating factor as adjuvant: Clinical and immunological responses in patients with pancreatic adenocarcinoma. Int J Cancer. 2001 May 1;92(3):441-50.

Wedén S, Klemp M, Gladhaug IP, Møller M, Eriksen JA, Gaudernack G, Buanes T. Long-term follow-up of patients with resected pancreatic cancer following vaccination against mutant K-ras. Int J Cancer. 2011 Mar 1;128(5):1120-8. doi: 10.1002/ijc.25449.

Responsible Party:	Targovax ASA
ClinicalTrials.gov Identifier:	NCT02261714 History of Changes
Other Study ID Numbers:	CT TG01-01
First Posted:	October 10, 2014
Last Update Posted:	October 13, 2017
Last Verified:	October 2017

Keywords provided by Targovax ASA:

Pancreatic cancer, resected; Vaccine; KRAS

Additional relevant MeSH terms:

Pancreatic Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Gemcitabine; Antimetabolites, Antineoplastic	Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antiviral Agents; Anti-Infective Agents; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs