Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.

Phase I Study of Tetrathiomolybdate in Combination With Carboplatin/Pemetrexed in Metastatic Non-small Cell Lung Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01837329
Recruitment Status : Completed
First Posted : April 23, 2013
Last Update Posted : July 19, 2019
Sponsor:
Information provided by (Responsible Party):
Megan Baumgart, University of Rochester

Tracking Information
First Submitted Date  ICMJE February 28, 2013
First Posted Date  ICMJE April 23, 2013
Last Update Posted Date July 19, 2019
Actual Study Start Date  ICMJE November 2013
Actual Primary Completion Date January 11, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 14, 2013)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: April 17, 2013)
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 newly diagnosed advanced adenocarcinoma of lung
Change History Complete list of historical versions of study NCT01837329 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 23, 2015)
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 17, 2013)
  • Percentage of participants with Complete Response or Partial Response based on RECIST criteria [ Time Frame: 3 years ]
    Determine efficacy of carboplatin and pemetrexed doublet in combination with TM in newly diagnosed advanced adenocarcinoma of the lung
  • Time from date of enrollment to disease progression or death [ Time Frame: 3 years ]
  • CTR1 status by immunohistochemistry [ Time Frame: 3 years ]
    Determine if pretreatment expression of copper transporter CTR1 by immunohistochemistry predicts clinical outcome following platinum-based chemotherapy in combination with TM
  • Platinum sensitivity [ Time Frame: 3 years ]
    Determine if ceruloplasmin level (a surrogate marker for copper status) is associated with platinum sensitivity
  • Platinum induced toxicity as measured by ceruloplasmin and copper levels [ Time Frame: 3 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase I Study of Tetrathiomolybdate in Combination With Carboplatin/Pemetrexed in Metastatic Non-small Cell Lung Cancer
Official Title  ICMJE 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
Brief Summary The main objective of this study is to determine recommended phase II dose and safety of tetrathiomolybdate (TM) in combination with carboplatin and pemetrexed in chemo-naive metastatic or recurrent non-squamous non-small cell lung cancer.
Detailed Description

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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non-Small Cell Lung Cancer
Intervention  ICMJE Drug: Tetrathiomolybdate

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
Study Arms  ICMJE Experimental: Tetrathiomolybdate

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.

Intervention: Drug: Tetrathiomolybdate
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 17, 2019)
26
Original Estimated Enrollment  ICMJE
 (submitted: April 17, 2013)
28
Actual Study Completion Date  ICMJE January 11, 2019
Actual Primary Completion Date January 11, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

>18 years old Performance status 0-1 Newly diagnosed stage IV non-squamous non-small cell lung cancer or recurrent disease after prior surgery and/or irradiation Patients must not have received prior chemotherapy for any stage non small cell lung cancer Brain metastases allowed provided they have been controlled for ≥ 2 weeks after completion of treatment and remain asymptomatic while off corticosteroids for at least 1 day Patient or primary care taker must be informed of and understand the investigational nature of this study and must sign and give written approved informed consent in accordance with institutional guidelines.

If patient is of childbearing potential, she or he must agree to practice an effective method of birth control prior to study entry, for the duration of study participation, and for 30 days after the last study dose.

Patient has adequate organ functions: serum bilirubin ≤ 2.0 mg/dL; alanine aminotransferase (ALT) ≤ 3 x upper limit of normal (ULN), or ALT ≤ 5 x ULN if the patient has hepatic metastasis; serum creatinine ≤ 1.5 mg/dL or a calculated creatinine clearance of at least 60 mL/min.

Patient has adequate bone marrow reserve: absolute neutrophil count ≥ 1,500, platelet count ≥ 100,000, and hemoglobin ≥ 9.0.

Exclusion Criteria:

Patient receiving any concurrent chemotherapy Patients who received platinum-based chemotherapy for any purpose Patients who had gastric bypass surgery Patients taking copper supplementation for medical reasons Medical and/or psychiatric problems of sufficient severity to limit full compliance with the study or expose patients to undue risk Patients with active and uncontrolled infection Patients with concomitant active malignancy requiring treatment with cytotoxic chemotherapy or radiation therapy (ongoing hormonal therapy for treatment of malignancy would not exclude patients from this trial) Known anaphylactic or severe hypersensitivity to study drugs or their analogs. Patient has failed to recover from any prior surgery within 4 weeks of study entry.

Patient has clinical evidence of copper deficiency (i.e. ceruloplasmin level was less than 15 mg/dL or free serum copper level less than 2.2 g/dL).

Patients with tumors that are epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma receptor tyrosine kinase (ALK) positive. If biopsy specimen is insufficient or inadequate for EGFR and/or ALK testing, subjects are eligible for the study.

Patients who are pregnant or lactating.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01837329
Other Study ID Numbers  ICMJE 46356
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Megan Baumgart, University of Rochester
Study Sponsor  ICMJE University of Rochester
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: David Dougherty, MD University of Rochester
PRS Account University of Rochester
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP