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

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

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

Study Overview

• Status: Completed
• Conditions: Pancreatic Cancer, Resected
• Intervention / Treatment: Biological: TG01; Biological: TG01

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 95 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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: 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

What is the study measuring?

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.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relationship Between (KRAS) Status and Clinical Efficacy	Relationship between KRAS status and recurrence	2 years

Collaborators and Investigators

• Sponsor: 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

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (Actual): May 1, 2019
• Study Completion (Actual): May 1, 2019

Study Registration Dates

• First Submitted: March 24, 2014
• First Submitted That Met QC Criteria: October 7, 2014
• First Posted (Estimate): October 10, 2014

Study Record Updates

• Last Update Posted (Actual): May 14, 2020
• Last Update Submitted That Met QC Criteria: May 13, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Vaccine; KRAS; Pancreatic cancer, resected
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms
• Other Study ID Numbers: CT TG01-01