Trial record 1 of 1 for:    Study of Carfilzomib With Irinotecan in Irinotecan-Sensitive Malignancies and Small Cell Lung Cancer Patients
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Study of Carfilzomib With Irinotecan in Irinotecan-Sensitive Malignancies and Small Cell Lung Cancer Patients

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Cancer Research and Biostatistics Clinical Trials Consortium
Sponsor:
Collaborators:
Lucille P. Markey Cancer Center at University of Kentucky
Washington University School of Medicine
Information provided by (Responsible Party):
Cancer Research and Biostatistics Clinical Trials Consortium
ClinicalTrials.gov Identifier:
NCT01941316
First received: August 19, 2013
Last updated: April 18, 2014
Last verified: April 2014
  Purpose

The purpose of this study is to determine a well-tolerated dose of Carfilzomib in combination with Irinotecan in subjects with relapsed small and non-small cell lung cancer or other irinotecan-sensitive cancers and to assess the 6 month survival of relapsed small cell lung cancer patients treated with this combination therapy.


Condition Intervention Phase
Small Cell Lung Carcinoma
Non Small Cell Lung Carcinoma
Irinotecan Sensitive Cancers
Drug: Carfilzomib
Drug: Irinotecan
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
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

Resource links provided by NLM:


Further study details as provided by Cancer Research and Biostatistics Clinical Trials Consortium:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    Assess 6 month survival of relapsed small cell lung cancer patients treated with Carfilzomib in combination with Irinotecan .


Secondary Outcome Measures:
  • Response rate [ Time Frame: up to 6 months ] [ Designated as safety issue: Yes ]
  • Progression-free survival [ Time Frame: up to 6 months ] [ Designated as safety issue: No ]
  • Safety/tolerability and the rates of specific adverse events [ Time Frame: up to 6 months ] [ Designated as safety issue: Yes ]

    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.

    Non-hematologic:

    • ≥ 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

    Hematologic:

    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Western blot analysis for Topoisomerase-I expression.

  • Biomarker endpoint [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    When available, banked tumor tissue for immunohistochemical expression of Topoisomerase-I.


Estimated Enrollment: 112
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)
Arms Assigned Interventions
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:

  1. Platinum sensitive disease: initial response to platinum-based chemotherapy with progression > 90 days after last treatment.
  2. Platinum refractory disease: No response to platinum-based chemotherapy or progression within 90 days of completing platinum-based therapy. Subjects that progressed during or within one month of completion of platinum-based chemotherapy will be excluded.
Drug: Carfilzomib
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:
  • CFZ
  • Kyprolis
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.
Other Names:
  • Camptosar
  • Campto

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have histologically or cytologically-confirmed diagnosis of progressive or recurrent malignancy as follows:
  • Phase Ib: advanced small or non-small cell lung cancer, or other cancer in which irinotecan therapy has been shown to be effective and for whom no curative therapy exists. Patients who received primary curative chemoradiation therapy, but who recur within the primary tumor site, previously radiated field or with distant metastases are also allowed to participate. Patients who have clinical evidence of recurrent cancer do not require a confirmatory biopsy to be eligible for this trial. No limit will be placed on prior regimens received, but prior irinotecan is not allowed.
  • Phase II: extensive stage small cell lung cancer with progression or recurrence after exactly one platinum-containing regimen. Patients who progressed during or within one month of completing platinum-based chemotherapy will be excluded. Patients who received primary curative chemoradiation therapy for limited disease, but who recur within the primary tumor site, previously radiated field or with distant metastases are also allowed to participate. Patients who have clinical evidence of recurrent small cell lung cancer do not require a confirmatory biopsy to be eligible for this trial. Prior irinotecan is not allowed.
  • Patients must have measurable disease per RECIST criteria 1.1 performed within 28 days prior to enrollment. All other required tests to assess non-measurable disease must be performed within 42 days prior to enrollment.
  • Patients with known brain metastases are eligible only if he/she has been treated for brain metastasis, are asymptomatic after treatment, have a stable CT or MRI of the brain within 28 days of enrollment and are not receiving corticosteroid therapy to control symptoms from brain metastasis. Only a non-enzyme inducing anticonvulsant (e.g., Keppra) will be permitted for those patients requiring anticonvulsants. (Topical and/or inhaled steroids are allowed.)
  • Patients may have received previous radiation therapy, but it must have been completed at least 21 days prior to enrollment and the patient should have recovered from all associated toxicities. Measurable or non-measurable disease must be present outside the previous radiation field or a new lesion inside the radiation port must be present.
  • Patients may have received prior surgery provided that at least 28 days have elapsed since major surgery (thoracic or other major surgeries) and the patient has recovered from all associated toxicities. Patients must have disease outside of the previous surgical resection area or a new lesion must be present.
  • Patients must have a serum creatinine ≤ the institutional upper limit of normal OR a creatinine clearance ≥ 60 cc/min, measured or calculated (Cockcroft-Gault formula), obtained within 14 days prior to registration.
  • Patients must have adequate hepatic function as documented by a bilirubin ≤ 2 x the institutional upper limit of normal, an alkaline phosphatase ≤ 2 x the institutional upper limit of normal, and an SGOT and SGPT ≤ 2 x the institutional upper limit of normal all obtained within 14 days prior to enrollment.
  • Patients must have an ANC ≥ 1,500/μl and a platelet count ≥ 100,000/μl obtained within 14 days prior to registration.
  • Patients must be 18 years of age or older.
  • Patients must have a Zubrod Performance Status as follows:

    1. Phase Ib: 0 or 1
    2. Phase II: 0, 1 or 2
  • Patients must not be pregnant or nursing. Women/men of reproductive potential must have agreed to use an effective contraceptive method (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.
  • Male subjects must agree to practice contraception.
  • All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.

Exclusion Criteria:

  • No prior irinotecan or carfilzomib
  • Must not have leptomeningeal metastases.
  • Must be no anticipated need for concurrent radiation therapy during protocol treatment.
  • Subjects that progressed during or within one month of completion of first-line platinum-based chemotherapy will be excluded.
  • Patients must not be pregnant or lactating females.
  • Must have had no major surgery within 28 days prior to enrollment.
  • Must not have acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to enrollment.
  • Must not have any known human immunodeficiency virus infection.
  • Must not have known active or clinically significant hepatitis A, B or C infection.
  • Must not have had any unstable angina or myocardial infarction within 4 months prior to enrollment, NYHA Class III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless subject has a pacemaker.
  • Must not have any uncontrolled hypertension or uncontrolled diabetes within 14 days prior to enrollment.
  • Must not have any evidence of other clinically active cancer and have no history of prior malignancy within the past 3 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason Grade 6 or less with stable prostate-specific antigen levels; or d) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder or benign tumors of the adrenal glands or pancreas.
  • Must not have any significant neuropathy (Grades 3-4, or Grade 2 with pain) within 14 days prior to enrollment.
  • Must not have any known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib).
  • Must have no contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to all anticoagulation and antiplatelet options, antiviral drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment.
  • Must not have any other clinically significant medical disease or condition that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent.
  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: NCT01941316

Contacts
Contact: Susanne M Arnold, MD 859-323-8043 smarno0@uky.edu
Contact: Grace Powell, BA 206-839-1790 gracep@crab.org

Locations
United States, Arizona
Cancer Treatment Centers of America, Western Regional Medical Center Recruiting
Goodyear, Arizona, United States, 85338
Contact: Brenda Noggy    623-323-3000    Clinicaltrials@ctca-hope.com   
Principal Investigator: Glen Weiss, MD         
The University of Arizona Cancer Center | University of Arizona Not yet recruiting
Tucson, Arizona, United States, 85719
Contact: Linda L Garland, MD    520-626-3434    lgarland@azcc.arizona.edu   
Principal Investigator: Linda L Garland, MD         
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, Colorado
National Jewish Health of Denver Not yet recruiting
Denver, Colorado, United States, 80206
Contact: Laurie Carr, MD    303-270-2601    carrl@njhealth.org   
Contact: James Jett, MD       JettJ@NJHealth.org   
Principal Investigator: Laurie Carr, MD         
United States, Kentucky
University of Kentucky Markey Cancer Center Recruiting
Lexington, Kentucky, United States, 40536
Contact: Susanne M Arnold, MD    859-323-8043    smarno0@uky.edu   
Principal Investigator: Susanne M Arnold, MD         
Norton Cancer Institute Not yet recruiting
Louisville, Kentucky, United States, 40202
Contact: John Hamm, MD    502-629-1234    John.hamm@nortonhealthcare.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    kjwillia1@im.wustl.edu   
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 Not yet 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         
Sponsors and Collaborators
Cancer Research and Biostatistics Clinical Trials Consortium
Lucille P. Markey Cancer Center at University of Kentucky
Washington University School of Medicine
Investigators
Principal Investigator: Susanne M Arnold, MD Lucille P. Markey Cancer Center at University of Kentucky
  More Information

No publications provided

Responsible Party: Cancer Research and Biostatistics Clinical Trials Consortium
ClinicalTrials.gov Identifier: NCT01941316     History of Changes
Other Study ID Numbers: CRAB CTC 11-001, CAR-IST-553
Study First Received: August 19, 2013
Last Updated: April 18, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Cancer Research and Biostatistics Clinical Trials Consortium:
Carfilzomib
Irinotecan
Small Cell Lung Cancer
Non Small Cell Lung Cancer
Ovarian Cancer
Gastric Cancer
Esophageal Cancer
Cervical Cancer

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Small Cell Lung Carcinoma
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Irinotecan
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Radiation-Sensitizing Agents
Therapeutic Uses
Topoisomerase I Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on October 21, 2014