TACTIC

The TACTIC study aims to evaluate the safety and efficacy of combining panitumumab with standard cisplatin and gemcitabine chemotherapy for advanced biliary tract cancer.

Gallbladder and bile duct cancers, collectively known as biliary tract cancers, are uncommon cancers, with only 774 people diagnosed in Australia in 2013. However, they have one of the lowest five-year survival rates of all cancers at less than 20%. Early detection of this type of cancer is unusual and the disease is commonly only diagnosed at advanced stages. The TACTIC trial aims to determine whether the addition of panitumumab to chemotherapy is safe and will improve the chance of survival for patients with biliary tract cancer.  TACTIC is currently in follow up and the final analysis was completed in 2016.

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Trial Status

Completed

Cancer Type

Gallbladder & Biliary Tract

Aim

The TACTIC study aims to evaluate the safety and efficacy of combining panitumumab with standard cisplatin and gemcitabine chemotherapy for advanced biliary tract cancer.

Summary

Gallbladder and bile duct cancers, collectively known as biliary tract cancers, are uncommon cancers, with only 774 people diagnosed in Australia in 2013. However, they have one of the lowest five-year survival rates of all cancers at less than 20%. Early detection of this type of cancer is unusual and the disease is commonly only diagnosed at advanced stages.

Patients with advanced biliary tract cancer are usually treated with two chemotherapy drugs: gemcitabine and cisplatin. However, there is increasing evidence that combination of conventional chemotherapy with novel agents can have an increased benefit.

In other cancer types, adding antibody treatments, such as panitumumab, to standard chemotherapy has resulted in an increase in the number of cancers shrinking or stabilising with treatment. Studies have observed that this may depend on whether the patient’s cancer had a certain gene (called KRAS wild-type). This highlights an area for further investigation in the context of biliary tract cancer patients.

The TACTIC trial aims to determine whether the addition of panitumumab to chemotherapy is safe and will improve the chance of survival for patients with biliary tract cancer.

TACTIC is currently in follow up and the final analysis was completed in 2016.

TACTIC has shown that panitumumab with standard chemotherapy appears to have some effect on the growth of biliary tract cancers with a specific gene type.  Further research is required to see if selection of patients based on more gene characteristics may improve the outcomes.

Trial Status

Completed

Cancer Type

Gallbladder & Biliary Tract

Protocol Title

Phase II trial of panitumumab, cisplatin and gemcitabine in biliary tract cancer.

Publication Reference

Ferraro D, Goldstein D, O’Connell RL, Zalcberg JR, Sjoquist KM, Tebbutt NC, Grimison P, McLachlan S, Lipton LL, Vasey P, Gebski VJ, Aiken C, Cronk M, Ng S, Karapetis CS, Shannon J. TACTIC: a multicentre, open-label, single-arm phase II trial of panitumumab, cisplatin, and gemcitabine in biliary tract cancer. Cancer Chemotherapy and Pharmacology 2016; 78(2): 361–367.

Conference Presentation Reference

Shannon J, Goldstein D, Wong N, Chinchen S, Sjoquist K, O’Connell R, Grimison P, McLachlan SA, Tebbutt NC, Lipton L, Vasey P., Cronk MF, Varma SC, Jefford M, Segelov E, Abdi E, Ng S, Karapetis C, Gebski V, Zalcberg J. A multicentre, phase II, open-label, single-arm trial of panitumumab, cisplatin and gemcitabine in biliary tract cancer: primary results of the AGITG TACTIC study. European Society for Medical Oncology Congress; 26–30 Sep 2014; Madrid.

Aim

The TACTIC study aims to evaluate the safety and efficacy of combining panitumumab with standard cisplatin and gemcitabine chemotherapy for advanced biliary tract cancer.

The primary objective of this study is to determine the objective clinical benefit (that is, combined rates of complete response, partial response and stable disease) of panitumumab in combination with gemcitabine and cisplatin in biliary tract cancer. The secondary objectives are to assess the tolerability and safety of the study treatment, overall survival, progression free survival, time to treatment failure, quality of life and tissue biomarkers of participating patients.

Background

Gallbladder and cholangiocarcinomas, collectively known as biliary tract cancers, are uncommon cancers, with only 774 people diagnosed in Australia in 2013. Biliary tract cancers have one of the lowest five-year survival rates of all cancers at 19.2%. Early detection of this type of cancer is unusual and the disease is commonly only diagnosed at advanced stages.

In other cancer types, adding antibody treatments to standard chemotherapy has resulted in an increase in the number of cancers shrinking or stabilising with treatment. Studies have observed that this may depend on whether the patient’s cancer had a certain gene (called KRAS wild-type). In addition, in other cancer types, panitumumab may be less effective in cancers with a KRAS mutation. Previous studies show that approximately 12% of biliary tract cancers have the KRAS mutation.

The purpose of the TACTIC study is to determine the activity and safety of a combination of treatments (gemcitabine, cisplatin and panitumumab) in patients with KRAS wild-type, locally advanced, metastatic or recurrent biliary tract cancer. The aim is to determine whether patients with the KRAS wild-type gene benefit from this treatment.

TACTIC is currently in follow up and the final analysis was completed in 2016.

Primary results were published in the journal Cancer Chemotherapy and Pharmacology in June 201678(2): 361–367.

TACTIC has shown that panitumumab with standard chemotherapy appears to have some effect on restricting the growth of biliary tract cancers with a specific gene type. When assessed at 12 weeks into the trial, 80% of the tumours had not grown during the treatment. The investigators considered the treatment active against this type of tumour and worthy of ongoing investigation.

Clinical Trial Design

The TACTIC study was a phase II open label, single arm study. Eligible participants had locally advanced, metastatic or recurrent biliary tract cancer with wild type KRAS.

Prior to the study, the patients were screened to find whether their cancer had the KRAS mutation and only patients without the mutation were accepted for the study.

All participants received standard chemotherapy with infusions of cisplatin and gemcitabine on two days every 3 weeks and panitumumab on one day. Treatment continued until disease progression, unacceptable toxicity, investigator discretion or patient request to cease treatment.

After the study treatment, patients were followed up 30 days after the last study drug administration. Subsequent follow up occurred every 12 weeks until disease progression or when the patient commenced new treatment.

Contact Email

tactic@ctc.usyd.edu.au

Principal Investigator

Dr Jenny Shannon (Nepean Hospital, Penrith NSW)

More Information

Available online at the Australian New Zealand Clinical Trial Registry (ANZCTR) here

Funding

Australasian Gastrointestinal Trials Group (AGITG)