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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 : Completed
First Posted : April 23, 2013
Last Update Posted : July 19, 2019
Sponsor:
Information provided by (Responsible Party):
Megan Baumgart, University of Rochester

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.

Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer Drug: Tetrathiomolybdate Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 26 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : November 2013
Actual Primary Completion Date : January 11, 2019
Actual Study Completion Date : January 11, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
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.

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




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. Time from date of enrollment to disease progression or death [ Time Frame: 3 years ]
  3. 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

  4. Platinum sensitivity and copper status [ Time Frame: 3 years ]
    Determine if ceruloplasmin level (a surrogate marker for copper status) is associated with platinum sensitivity

  5. Platinum induced toxicity and copper status [ Time Frame: 3 years ]
    Determine if ceruloplasmin level is associated with platinum-induced toxicity.

  6. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.


Information from the National Library of Medicine

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


Locations
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United States, New York
University of Rochester
Rochester, New York, United States, 14642
Sponsors and Collaborators
University of Rochester
Investigators
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Principal Investigator: David Dougherty, MD University of Rochester

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Responsible Party: Megan Baumgart, Assistant Professor, University of Rochester
ClinicalTrials.gov Identifier: NCT01837329     History of Changes
Other Study ID Numbers: 46356
First Posted: April 23, 2013    Key Record Dates
Last Update Posted: July 19, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by Megan Baumgart, University of Rochester:
Non-Squamous
NSCLC
Adenocarcinoma
Lung Cancer
Tetrathiomolybdate
Copper
Carboplatin
Pemetrexed Platinum
Newly Diagnosed
Chemo-naive
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Molybdenum
Carboplatin
Pemetrexed
Tetrathiomolybdate
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors
Chelating Agents
Sequestering Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Trace Elements
Micronutrients
Nutrients