Study of Carfilzomib With Irinotecan in Irinotecan-Sensitive Malignancies and Small Cell Lung Cancer Patients
Small Cell Lung Carcinoma
Non Small Cell Lung Carcinoma
Irinotecan Sensitive Cancers
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase 1b/II Trial of Carfilzomib With Irinotecan in Irinotecan-Sensitive Malignancies (Phase Ib) and Small Cell Lung Cancer Patients (Phase II) Who Have Progressed on Prior Platinum-based Chemotherapy|
- Phase 1b: Determine maximum tolerated dose of Carfilzomib in combination with Irinotecan in subjects with relapsed small and non-small cell lung cancer or other irinotecan-sensitive cancers. [ Time Frame: 28 Days ]Determine maximum tolerated dose (MTD) of Carfilzomib in combination with Irinotecan in subjects with relapsed small and non-small cell lung cancer or other irinotecan-sensitive cancers.
- Phase II: Assess 6 month survival of relapsed small cell lung cancer patients treated with Carfilzomib in combination with irinotecan. [ Time Frame: up to 6 Months ]Assess 6 month survival of relapsed small cell lung cancer patients treated with Carfilzomib in combination with Irinotecan .
- Response rate [ Time Frame: up to 6 months ]
- Progression-free survival [ Time Frame: up to 6 months ]
- Safety/tolerability and the rates of specific adverse events [ Time Frame: up to 6 months ]
Number of patients with adverse events as a measure of safety and tolerability. Dose Limiting Toxicity (DLT) adverse events related to Carfilzomib in combination with Irinotecaen administration. Subjects will be evaluated for toxicity according to the Common Terminology Criteria for Adverse Events (CTCAE) of version 4.0.
A DLT is defined as any of the treatment emergent toxicities with attribution to one or more of the study drugs that occur during Cycle 1.
- ≥ Grade 2 neuropathy with pain
- ≥ Any Grade 3 or 4 toxicity (excluding nausea, vomiting, diarrhea or grade 3 fatigue)
- ≥ Grade 3 nausea, vomiting, or diarrhea lasting > 7 days despite maximal antiemetic/antidiarrheal therapy
- ≥ Grade 4 fatigue lasting for ≥ 7 days
Grade 4 neutropenia lasting for ≥ 7 days, Febrile neutropenia, Grade 4 thrombocytopenia lasting ≥ 7 days despite dose delay, Grade 3-4 thrombocytopenia associated with bleeding
- Biomarker endpoint [ Time Frame: Day 1: pre-dose, 90min, 2hr., 5.5hr post dose; Day 2: pre-dose ]Carfilzomib proteasome chymotrypsin-like activity in PBMC and LMP7 and b5 expression.
- Biomarker endpoint [ Time Frame: Day 1: pre-dose, 90min, 2hr., 5.5hr post dose; Day 2: pre-dose ]Irinotecan-mediated DNA damage by immunofluorescence analysis for gamma-H2AX staining.
- Biomarker endpoint [ Time Frame: Day 1: pre-dose, 90min, 2hr., 5.5hr post dose; Day 2: pre-dose ]Western blot analysis for Topoisomerase-I expression.
- Biomarker endpoint [ Time Frame: Day 1 ]When available, banked tumor tissue for immunohistochemical expression of Topoisomerase-I.
|Study Start Date:||November 2013|
|Estimated Study Completion Date:||December 2016|
|Estimated Primary Completion Date:||December 2016 (Final data collection date for primary outcome measure)|
Experimental: Phase 1b or Phase II
Phase 1b: Standard 3+3 design using five dose levels of Carfilzomib in combination with a single dose of Irinotecan. Two dose de-escalations are built into the protocol for safety.
Phase II: Stratified, single arm trial using MTD from Phase Ib, in small cell lung cancer patients who have relapsed on a prior platinum regimen.
Stratification for phase II component:
20/ * mg/m2, IV infusion (over 30 min), on days 1, 2, 8, 9, 15 and 16 of each 28 day cycle. Number of cycles: 6, or until progression, or unacceptable toxicity, or treatment delay for any reason greater than 3 weeks.
Other Names:Drug: Irinotecan
125 mg/m2, IV infusion (over 90 min), on days 1, 8, 15 of each 28 day cycle. Number of cycles: 6, or until progression, or unacceptable toxicity, or treatment delay for any reason greater than 3 weeks.
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT01941316
|Contact: Susanne M Arnold, MDemail@example.com|
|Contact: Grace Powell, BAfirstname.lastname@example.org|
|United States, Arizona|
|Cancer Treatment Centers of America, Western Regional Medical Center||Completed|
|Goodyear, Arizona, United States, 85338|
|United States, California|
|Cedars-Sinai Medical Center||Not yet recruiting|
|Los Angeles, California, United States, 90048|
|Contact: Alain Mita, MD 310-967-0600 Alain.Mita@cshs.org|
|Principal Investigator: Alain Mita, MD|
|UCLA||Not yet recruiting|
|Santa Monica, California, United States, 90404|
|Contact: Jonathan Goldman, MD 310-633-8400 JWGoldman@mednet.ucla.edu|
|Principal Investigator: Jonathan Goldman, MD|
|United States, Kentucky|
|University of Kentucky Markey Cancer Center||Recruiting|
|Lexington, Kentucky, United States, 40536|
|Contact: Susanne M Arnold, MD 859-323-8043 email@example.com|
|Principal Investigator: Susanne M Arnold, MD|
|Norton Cancer Institute||Recruiting|
|Louisville, Kentucky, United States, 40202|
|Contact: John Hamm, MD 502-629-1234 John.firstname.lastname@example.org|
|Principal Investigator: John Hamm, MD|
|United States, Missouri|
|Washington University School of Medicine||Recruiting|
|St. Louis, Missouri, United States, 63110|
|Contact: Maria Baggstrom, MD MBaggstr@DOM.wustl.edu|
|Contact: Kristina Williams (314) 362-6963 email@example.com|
|Principal Investigator: Maria Baggstrom, MD|
|United States, Oregon|
|Providence Portland Medical Center | Earle A. Chiles Research Institute||Recruiting|
|Portland, Oregon, United States, 97213|
|Contact: Rachel E Sanborn, MD 503-215-5696 Rachel.Sanborn@providence.org|
|Principal Investigator: Rachel E Sanborn, MD|
|United States, Washington|
|Virginia Mason Cancer Institute||Recruiting|
|Seattle, Washington, United States, 98111|
|Contact: Kamal Chatta, MD 206-341-0037 Kamal.Chatta@vmmc.org|
|Principal Investigator: Kamal Chatta, MD|
|United States, Wisconsin|
|Aurora Research Institute | Aurora Cancer Care||Recruiting|
|Wauwatosa, Wisconsin, United States, 53226|
|Contact: Michael Thompson, MD, PhD 414-219-7838 Michael.A.Thompson@aurora.org|
|Principal Investigator: Michael Thomson, MD, PhD|
|Principal Investigator:||Susanne M Arnold, MD||Lucille P. Markey Cancer Center at University of Kentucky|