Phase I Study of Tetrathiomolybdate in Combination With Carboplatin/Pemetrexed in Metastatic Non-small Cell Lung Cancer
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|ClinicalTrials.gov Identifier: NCT01837329|
Recruitment Status : Recruiting
First Posted : April 23, 2013
Last Update Posted : October 20, 2017
|Condition or disease||Intervention/treatment||Phase|
|Non-Small Cell Lung Cancer||Drug: Tetrathiomolybdate||Phase 1|
Platinum resistance is a major limitation in the treatment of advanced non-small cell lung cancer. Previous studies suggest that reduced tumor platinum levels may significantly contribute to platinum resistance and thus poor outcome following platinum-based chemotherapy in lung cancer.
Tetrathiomolybdate (TM) is a fast-acting copper chelator that has been under significant investigation as an anti-cancer strategy due to its anti-angiogenic property. Furthermore, more recent preclinical evidence suggests that combining TM with platinum drugs resulted in higher intratumoral platinum concentration and greater tumor response. The oncologists at the University of Rochester are studying addition of TM to commonly used 1st line platinum-based doublet, carboplatin/pemetrexed, in patients with non-squamous non-small cell lung cancer.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||28 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Study of Tetrathiomolybdate (TM) in Combination With Carboplatin and Pemetrexed in Chemo-Naive Metastatic or Recurrent Non-Squamous Non-Small Cell Lung Cancer|
|Study Start Date :||November 2013|
|Estimated Primary Completion Date :||October 2018|
|Estimated Study Completion Date :||October 2018|
Dose Escalation - It is aimed at determining the maximum tolerated dose of TM in combination with carboplatin and pemetrexed.
Dose Expansion - The dose expansion portion of the study will begin after completion of the dose escalation phase.
Dose Escalation - Dose level -1: 20 mg TM orally 3 x daily x 21 days in combination with carboplatin IV area under the curve (AUC) = 6 and pemetrexed IV 500/mgm2 day 1 x 1 cycle.
Dose level 1: 40 mg TM orally 3 x daily x 21 days in combination with carboplatin IV AUC = 6 and pemetrexed IV 500 mg/m2 day 1 x 1 cycle.
Dose level 2: 60 mg TM orally 3 x daily x 21 days in combination with carboplatin IV AUC = 6 and pemetrexed IV 500 mg/m2 day 1 x 1 cycle.
Patients in the dose-expansion cohort will continue on carboplatin and pemetrexed (without TM) at the discretion of the treating physician.
Dose Expansion - Maximum tolerated dose of TM determined from the dose-escalation cohorts combined with carboplatin IV AUC = 6 and pemetrexed IV 500 mg/m2 day 1 x 4 cycles.
Other Name: TM
- Number of participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 3 years ]Determine phase II dose and safety of TM in combination with carboplatin and pemetrexed in chemo-naive metastatic or recurrent non-squamous non-small cell lung cancer.
- Percentage of participants with Complete Response or Partial Response [ Time Frame: 3 years ]Determine efficacy of carboplatin and pemetrexed doublet in combination with TM in chemo-naive metastatic or recurrent non-small cell lung cancer.
- Time from date of enrollment to disease progression or death [ Time Frame: 3 years ]
- Expression of copper transporter by immunohistochemistry [ Time Frame: 3 years ]Determine if pretreatment expression of copper transporter by immunohistochemistry predicts clinical outcome following platinum-based chemotherapy in combination with TM
- Platinum sensitivity and copper status [ Time Frame: 3 years ]Determine if ceruloplasmin level (a surrogate marker for copper status) is associated with platinum sensitivity
- Platinum induced toxicity and copper status [ Time Frame: 3 years ]Determine if ceruloplasmin level is associated with platinum-induced toxicity.
- Impact on blood mineral levels. [ Time Frame: 3 years ]To determine if Tetrathiomolybdate affects serum copper, iron, total iron binding capacity, ferritin or zinc levels when combined with platinum-based chemotherapy.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01837329
|Contact: David Dougherty, M.D.||585-275-0394||David_Dougherty@urmc.rochester.edu|
|United States, New York|
|University of Rochester||Recruiting|
|Rochester, New York, United States, 14642|
|Contact: Amy Jasek 585-273-1912 Amy_Jasek@urmc.rochester.edu|
|Principal Investigator: David Dougherty, MD|
|Principal Investigator:||David Dougherty, MD||University of Rochester|