Clinical trial NCT02261714: Antigen-specific Cancer Immunotherapy (TG01) and Gemcitabine as Adjuvant Therapy in Resected Pancreatic Cancer
Official title: A Phase I/II Trial of TG01 and Gemcitabine as Adjuvant Therapy for Treating Patients With Resected Adenocarcinoma of the Pancreas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Pancreatic Cancer, Resected
Keywords: Pancreatic cancer, resected
Vaccine
KRAS
Lead sponsor: Targovax ASA
Sponsor class: INDUSTRY
First posted: 2014-10-10
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility 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

Primary outcomes:
measure: Patients' Safety During Study
timeFrame: 2 years
measure: Patients' Immune Response
timeFrame: During the 2 years of treatment
Secondary outcomes:
measure: Clinical Efficacy
timeFrame: DFS was followed for up to 2 years and OS until last patient included had been in the study for 3 years.
Other outcomes:
measure: Relationship Between (KRAS) Status and Clinical Efficacy
timeFrame: 2 years
Locations:
city: Oslo
country: Norway
facility: Oslo University Hospital HF the Norwegian Radium Hospital
city: Madrid
country: Spain
facility: Centro Integral Oncologico Clara Campal / Hospital HM Universitario Sanchinarro
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth University Hospital / Edgaston /
city: Liverpool
country: United Kingdom
facility: University of Liverpool / Molecular and Clinical Cancer Medicine
city: Manchester
country: United Kingdom
facility: University of Manchester / The Christie NHS Foundation Trust
Study officials:
affiliation: University of Liverpool Molecular and Clinical Cancer Medicine /UCD Duncan Building / Daulby Street / Liverpool
name: Daniel PALMER
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Manchester / The Christie NHS Foundation Trust /Wilmslow Road / Manchester
name: Juan VALLE
role: PRINCIPAL_INVESTIGATOR
affiliation: Oslo University Hospital HF / the Norwegian Radium Hospital / Ullernchausseen 70 / Oslo
name: Svein DUELAND
role: PRINCIPAL_INVESTIGATOR
affiliation: Queen Elizabeth University Hospital / Edgaston / Birmingham
name: Yuk Ting MA
role: PRINCIPAL_INVESTIGATOR
affiliation: Centro Integral Oncologico Clara Campal / Hospital HM Universitario Sanchinarro / Madrid
name: Emiliano Calvo
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gjertsen MK, Buanes T, Rosseland AR, Bakka A, Gladhaug I, Soreide O, Eriksen JA, Moller 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. doi: 10.1002/ijc.1205.
citation: Weden S, Klemp M, Gladhaug IP, Moller 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.
citation: Palmer DH, Valle JW, Ma YT, Faluyi O, Neoptolemos JP, Jensen Gjertsen T, Iversen B, Amund Eriksen J, Moller AS, Aksnes AK, Miller R, Dueland S. TG01/GM-CSF and adjuvant gemcitabine in patients with resected RAS-mutant adenocarcinoma of the pancreas (CT TG01-01): a single-arm, phase 1/2 trial. Br J Cancer. 2020 Mar;122(7):971-977. doi: 10.1038/s41416-020-0752-7. Epub 2020 Feb 17.