• TACTIC
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Trial Status

Completed

Cancer Type

Gallbladder & Biliary Tract

Protocol Title

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

Purpose of the Study

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. 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.

Eligibility Criteria

Inclusion Criteria

  1. Histologic or cytologic diagnosis of adenocarcinoma of the gallbladder or intra/extrahepatic bile ducts with locally advanced or metastatic disease
  2. Patients must have received no prior chemotherapy or biological therapy for advanced disease;
  3. Prior radiotherapy must be completed at least 4 weeks before study enrolment.
  4. Patients must have recovered from the acute toxic effects of the treatment prior to study enrolment;
  5. Patient compliance and geographic proximity that allows adequate follow-up;
  6. Signed informed consent from patient or legal representative.
  7. Patients available to complete study requirements (visits, tests, evaluations and follow-up procedures) in a timely manner.
  8. Male and female patients with reproductive potential must use a reliable contraceptive method if appropriate (eg, intrauterine device [IUD], birth control pills, or barrier device) during and for 3 months after the study. Females with childbearing potential must have a negative urine pregnancy test within 7 days prior to study enrolment.
  9. Minimum age; 18

Exclusion Criteria

  1. Medical or psychiatric conditions that compromise the patient’s ability to give informed consent or comply with the study protocol;
  2. Heart failure, angina pectoris or arrhythmia that are poorly controlled
  3. Active infection that in the opinion of the investigator would compromise the patient’s ability to tolerate therapy, especially uncontrolled biliary tract infections;
  4. Poorly controlled diabetes mellitus;
  5. Interstitial lung disease
  6. Any other serious concomitant disorders that would compromise the safety of the patient or compromise the patient’s ability to complete the study, at the discretion of the investigator;
  7. Pregnancy or breast feeding or unwilling / unable to practice adequate contraception
  8. Documented brain metastasis.

More Information

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

Principal Investigator

Dr Jenny Shannon

Funding

Australasian Gastro-Intestinal Trials Group (AGITG)

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 2016 – 78(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)