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

NCT ID: NCT02261714

Last Updated: 2020-05-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-12-31
• Study Completion Date: 2019-05-31

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

Conditions

Pancreatic Cancer, Resected

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

TG01/GM-CSF and Gemcitabine

Group Type: EXPERIMENTAL

TG01

Intervention Type: BIOLOGICAL

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

TG01

Intervention Type: BIOLOGICAL

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

Interventions

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

Intervention Type: 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

Intervention Type: BIOLOGICAL

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Targovax ASA

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Daniel PALMER

Role: PRINCIPAL_INVESTIGATOR

University of Liverpool Molecular and Clinical Cancer Medicine /UCD Duncan Building / Daulby Street / Liverpool

Juan VALLE

Role: PRINCIPAL_INVESTIGATOR

University of Manchester / The Christie NHS Foundation Trust /Wilmslow Road / Manchester

Svein DUELAND

Role: PRINCIPAL_INVESTIGATOR

Oslo University Hospital HF / the Norwegian Radium Hospital / Ullernchausseen 70 / Oslo

Yuk Ting MA

Role: PRINCIPAL_INVESTIGATOR

Queen Elizabeth University Hospital / Edgaston / Birmingham

Emiliano Calvo

Role: PRINCIPAL_INVESTIGATOR

Centro Integral Oncologico Clara Campal / Hospital HM Universitario Sanchinarro / Madrid

Locations

Oslo University Hospital HF the Norwegian Radium Hospital

Oslo, , Norway

Centro Integral Oncologico Clara Campal / Hospital HM Universitario Sanchinarro

Madrid, , Spain

Queen Elizabeth University Hospital / Edgaston /

Birmingham, , United Kingdom

University of Liverpool / Molecular and Clinical Cancer Medicine

Liverpool, , United Kingdom

University of Manchester / The Christie NHS Foundation Trust

Manchester, , United Kingdom

Countries

Norway; Spain; United Kingdom

References

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.

Reference Type: BACKGROUND

PMID: 11291084 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 20473937 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32063605 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

CT TG01-01

Identifier Type: -

Identifier Source: org_study_id