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

Non-Small Cell Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01837329
• Other study ID #: 46356
• Status: Completed
• Phase: Phase 1
• Start date: November 2013
• Est. completion date: January 11, 2019

Study information

• Verified date: July 2019
• Source: University of Rochester
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: January 11, 2019
• Est. primary completion date: January 11, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

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.

Locations

Country	Name	City	State
United States	University of Rochester	Rochester	New York

Sponsors (1)

Lead Sponsor	Collaborator
University of Rochester

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with Adverse Events as a Measure of Safety and Tolerability	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.	3 years
Secondary	Percentage of participants with Complete Response or Partial Response	Determine efficacy of carboplatin and pemetrexed doublet in combination with TM in chemo-naive metastatic or recurrent non-small cell lung cancer.	3 years
Secondary	Time from date of enrollment to disease progression or death		3 years
Secondary	Expression of copper transporter by immunohistochemistry	Determine if pretreatment expression of copper transporter by immunohistochemistry predicts clinical outcome following platinum-based chemotherapy in combination with TM	3 years
Secondary	Platinum sensitivity and copper status	Determine if ceruloplasmin level (a surrogate marker for copper status) is associated with platinum sensitivity	3 years
Secondary	Platinum induced toxicity and copper status	Determine if ceruloplasmin level is associated with platinum-induced toxicity.	3 years
Secondary	Impact on blood mineral levels.	To determine if Tetrathiomolybdate affects serum copper, iron, total iron binding capacity, ferritin or zinc levels when combined with platinum-based chemotherapy.	3 years