Clinical trial NCT00312819: Initial Assessment of the Effect of the Addition of Disulfiram (Antabuse) to Standard Chemotherapy in Lung Cancer
Official title: Randomized Phase 2 Trial of Treatment of Advanced Non Small Cell Lung Carcinoma With/Without Disulfiram and Cisplatin Navelbine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Non-small Cell Lung Cancer
Keywords: Non-small cel lung cancer
chemotherapy
randomized phaseII
disulfiram
antiangiogenesis
placebo
Lead sponsor: Hadassah Medical Organization
Sponsor class: OTHER
Collaborators: name: Augusta Hospital, Berlin
First posted: 2006-04-11
Enrollment: 60
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Recent studies in laboratory animals demonstrate the ability of disulfiram to significantly inhibit the growth and metastasis of a mouse model of lung cancer. Work with cells in vitro support the idea that this inhibition is mainly due to the inhibition of angiogenesis - the formation of new blood vessels in the tumor. Furthermore, it was found out that the best effect has been obtained when disulfiram has been used not at the highest dose but at an optimal dose, which is smaller. Thus, this trial will assess the addition of disulfiram to chemotherapy in non-small cell lung cancer (NSCLCA).

Detailed description: Metastatic non small cell lung cancer remains a deadly disease with median survival times of several months. Any treatment which can prolong patients' survival without causing severe side effects is of course an important addition to our limited arsenal in the fight against this disease. A recent article by Marikowsky and colleagues extended significantly our knowledge regarding the possible activity of disulfiram (well known in its commercial name Antabuse) as an anticancer agent (Marikowsky et al Int J of cancer 97 :34 2002). In this article it was demonstrated that disulfiram has potent antitumor activity and that it can act as a significant inhbitor of angiogenesis.

Since disulfiram has been well tolerated by thousands of patients, and there are observations that anti angiogenic therapy enhances the effect of chemotherapy (for example bevacizumab in combination with chemotherapy in colon carcinoma) we decided to conduct a clinical trial assessing the effect of the addition of this drug at moderate doses to chemotherapy which is used as one of the standard therapies in lung cancer. In order to obtain information regarding the effect of the addition of this drug, only 50% of the patients will be treated with the drug and the rest will be treated with placebo.

Eligibility criteria: Inclusion Criteria:

* Metastatic non-small cell lung cancer
* Previously untreated
* ECOG performance status (PS) 0-1
* Liver function tests within the norm

Exclusion Criteria:

* Over 18
* Willingness to abstain from alcohol
* Not pregnant
* Without a psychiatric history

Primary outcomes:
measure: tumor response disease free survival survival
timeFrame: 3 years
Secondary outcomes:
measure: Clinical response
measure: treatment tolerance
Other outcomes:
Locations:
city: Kfar Saba
country: Israel
facility: Oncology Institute Meir Medical Center
Study officials:
affiliation: Hadassah Medical Center Ein Kerem
name: Hovav Nechushtan, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hadassah Ein Kerem Medical Center
name: Nili Peylan-Ramu, MD
role: STUDY_CHAIR
affiliation: Meir Medical Center Kfar Saba
name: Maya Gotfrid, MD
role: STUDY_CHAIR
References:
citation: Marikovsky M, Nevo N, Vadai E, Harris-Cerruti C. Cu/Zn superoxide dismutase plays a role in angiogenesis. Int J Cancer. 2002 Jan 1;97(1):34-41. doi: 10.1002/ijc.1565.
citation: Nechushtan H, Hamamreh Y, Nidal S, Gotfried M, Baron A, Shalev YI, Nisman B, Peretz T, Peylan-Ramu N. A phase IIb trial assessing the addition of disulfiram to chemotherapy for the treatment of metastatic non-small cell lung cancer. Oncologist. 2015 Apr;20(4):366-7. doi: 10.1634/theoncologist.2014-0424. Epub 2015 Mar 16.