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

NCT01837329 | Completed Phase 1 DMC

• 1 other identifier: 46356
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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.

Conditions

Non-Small Cell Lung Cancer

Keywords

Non-Squamous; NSCLC; Adenocarcinoma; Lung Cancer; Tetrathiomolybdate; Copper; Carboplatin; Pemetrexed Platinum; Newly Diagnosed; Chemo-naive

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Percentage of participants with Complete Response or Partial Response

  3 years

• Time from date of enrollment to disease progression or death

  3 years

• Expression of copper transporter by immunohistochemistry

  3 years

• Platinum sensitivity and copper status

  3 years

• Platinum induced toxicity and copper status

  3 years

Study Arms (1)

Tetrathiomolybdate

EXPERIMENTAL

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

Interventions

Tetrathiomolybdate DRUG

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.

Also known as: TM

Tetrathiomolybdate

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \>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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Rochester: lead

Study Sites (1)

University of Rochester

Rochester, New York, 14642, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Adenocarcinoma; Lung Neoplasms

Interventions

tetrathiomolybdate

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Study Officials

• David Dougherty, MD

  University of Rochester

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: February 28, 2013
• First Posted: April 23, 2013
• Study Start: November 1, 2013
• Primary Completion: January 11, 2019
• Study Completion: January 11, 2019
• Last Updated: July 19, 2019

Record last verified: 2019-07

Locations

US (1)