Trientine and Carboplatin in Advanced Malignancies

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01178112
First received: August 6, 2010
Last updated: August 19, 2014
Last verified: August 2014
  Purpose

The goal of this clinical research study is to find the highest tolerable dose of the combination of trientine and carboplatin that can be given to patients with advanced cancer. The safety of this drug combination will also be studied.


Condition Intervention Phase
Advanced Cancers
Drug: Trientine
Drug: Carboplatin
Drug: Trientine MTD
Drug: Carboplatin MTD
Other: PK Testing
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Trientine and Carboplatin in Patients With Advanced Malignancies

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) of Carboplatin with Trientine [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
    MTD defined by dose limiting toxicities (DLTs) that occur in the first cycle (4 weeks). DLT defined as treatment-related grade 3 or greater nonhematological toxicity other than nausea, vomiting, or fatigue.


Secondary Outcome Measures:
  • Treatment Response of Maximum Tolerated Dose (MTD) of Carboplatin with Trientine [ Time Frame: After 2, 28 day cycles ] [ Designated as safety issue: No ]
    Categorization of response based on immune-related response criteria and Response Evaluation Criteria in Solid Tumors (RECIST).


Enrollment: 56
Study Start Date: July 2010
Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Trientine + Carboplatin MTD Group
Trientine starting dose 750 mg by mouth four times a day, two times with meals and two times without meals for 28 days. Carboplatin maximum tolerated dose found in MTD Dose Escalation Group.
Drug: Trientine
Starting dose 750 mg by mouth four times a day, two times with meals and two times without meals for 28 days.
Drug: Carboplatin
Starting dose area under curve (AUC) 4 by vein over two hours on day 1, and once every 28 days.
Other Name: Paraplatin
Experimental: MTD Expansion Group
Trientine maximum tolerated dose found in MTD Dose Escalation Group; Carboplatin PK Group A, instead of starting on Day 1 of Cycle 1, starts taking trientine daily beginning on Day 2 of Cycle 1. Trientine PK Group B, 1500 mg of trientine is given once without food on Day 21 of Cycle 1 and once without food after the completion of carboplatin on Day 1 of Cycle 2. Carboplatin maximum tolerated dose found in MTD Dose Escalation Group
Drug: Trientine MTD
Maximum tolerated dose found in MTD Dose Escalation Group; Carboplatin PK Group A, instead of starting on Day 1 of Cycle 1, starts taking trientine daily beginning on Day 2 of Cycle 1. Trientine PK Group B, 1500 mg of trientine is given once without food on Day 21 of Cycle 1 and once without food after the completion of carboplatin on Day 1 of Cycle 2.
Drug: Carboplatin MTD
Maximum tolerated dose found in MTD Dose Escalation Group
Other Name: Paraplatin
Experimental: Carboplatin PK Expansion Group
Trientine maximum tolerated dose found in MTD Dose Escalation Group; Carboplatin PK Group A, instead of starting on Day 1 of Cycle 1, starts taking trientine daily beginning on Day 2 of Cycle 1. Trientine PK Group B, 1500 mg of trientine is given once without food on Day 21 of Cycle 1 and once without food after the completion of carboplatin on Day 1 of Cycle 2. Carboplatin maximum tolerated dose found in MTD Dose Escalation Group. PK testing blood samples of 4 mL at following time points: 0, 30, 60 minutes, 2, 3, 4, 6, and 24 hours.
Drug: Trientine MTD
Maximum tolerated dose found in MTD Dose Escalation Group; Carboplatin PK Group A, instead of starting on Day 1 of Cycle 1, starts taking trientine daily beginning on Day 2 of Cycle 1. Trientine PK Group B, 1500 mg of trientine is given once without food on Day 21 of Cycle 1 and once without food after the completion of carboplatin on Day 1 of Cycle 2.
Drug: Carboplatin MTD
Maximum tolerated dose found in MTD Dose Escalation Group
Other Name: Paraplatin
Other: PK Testing
Blood samples of 4 mL at following time points: 0, 30, 60 minutes, 2, 3, 4, 6, and 24 hours.
Experimental: Trientine PK Expansion Group
Trientine maximum tolerated dose found in MTD Dose Escalation Group; Carboplatin PK Group A, instead of starting on Day 1 of Cycle 1, starts taking trientine daily beginning on Day 2 of Cycle 1. Trientine PK Group B, 1500 mg of trientine is given once without food on Day 21 of Cycle 1 and once without food after the completion of carboplatin on Day 1 of Cycle 2. Carboplatin maximum tolerated dose found in MTD Dose Escalation Group. PK testing blood samples of 4 mL at following time points: 0, 30, 60 minutes, 2, 3, 4, 6, and 24 hours.
Drug: Trientine MTD
Maximum tolerated dose found in MTD Dose Escalation Group; Carboplatin PK Group A, instead of starting on Day 1 of Cycle 1, starts taking trientine daily beginning on Day 2 of Cycle 1. Trientine PK Group B, 1500 mg of trientine is given once without food on Day 21 of Cycle 1 and once without food after the completion of carboplatin on Day 1 of Cycle 2.
Drug: Carboplatin MTD
Maximum tolerated dose found in MTD Dose Escalation Group
Other Name: Paraplatin
Other: PK Testing
Blood samples of 4 mL at following time points: 0, 30, 60 minutes, 2, 3, 4, 6, and 24 hours.

  Show Detailed Description

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patient must have an advanced malignancy that has either failed one or more prior therapies, or for whom there is no established standard of care therapy that prolongs survival by at least 3 months.
  2. Only in 1 of 3 expansion cohorts, we will plan to enroll 14 subjects with platinum-resistant malignancy. Patient with platinum-resistant malignancy is defined to have had a treatment-free interval of less than 6 months following a platinum-based regimen.
  3. Patient of any age and any gender. However, those who are 12 years old or younger will be eligible after consultation with their pediatric physicians regarding dose initiation and modification of trientine.
  4. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
  5. Patient is willing to comply with study procedures and follow-up examinations.
  6. Patient or primary care taker must be informed of the investigational nature of this study and must sign and give written Institutional Review Board (IRB)-approved informed consent in accordance with institutional guidelines.
  7. 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.
  8. Patient has adequate organ functions: serum bilirubin </= 2.0 mg/dL; 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.
  9. Patient has adequate bone marrow reserve: absolute neutrophil count (ANC) >/= 1,500 /ul, Platelet count >/= 100,000 /ul , and Hemoglobin >/= 9.0 g/dL.

Exclusion Criteria:

  1. Patient receiving any concurrent chemotherapy.
  2. Underlying medical condition that might be aggravated by treatment or that cannot be controlled, such as active, uncontrolled, serious infection and cardiac dysfunction.
  3. Medical and/or psychiatric problems of sufficient severity to limit full compliance with the study or expose patients to undue risk.
  4. Known anaphylactic or severe hypersensitivity to study drugs or their analogs.
  5. Patient has failed to recover from any prior surgery within 4 weeks of study entry.
  6. Patient is pregnant or lactating.
  7. Patient has had any treatment specific for tumor control within 3 weeks of dosing with investigational drugs and cytotoxic agents, or within 2 weeks of cytotoxic agent given weekly, or within 6 weeks of nitrosoureas or mitomycin C, or within 5 half-lives of biological targeted agents with half-lives and pharmacodynamic effects lasting less than 5 days (that includes, but is not limited to, erlotinib, sorafenib, sunitinib, bortezomib, and other similar agents), or failure to recover from the toxic effect of any of these therapies prior to study entry.
  8. Patient has any signs of intestinal obstruction interfering with nutrition.
  9. Patient has a known history of central nervous system (CNS) metastasis unless the patient has had treatment with surgery or radiation therapy, and is neurologically stable.
  10. Patient is not able to swallow oral medication.
  11. 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 ug/dL).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01178112

Locations
United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Siqing Fu, MD, PHD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided by M.D. Anderson Cancer Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01178112     History of Changes
Other Study ID Numbers: 2010-0258, NCI-2012-01787
Study First Received: August 6, 2010
Last Updated: August 19, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Metastasis
Carboplatin
Trientine
Chemotherapy

Additional relevant MeSH terms:
Carboplatin
Trientine
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 19, 2014