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

Who is this study for? Patients with irinotecan-sensitive malignancies and small cell lung cancer
What treatments are being studied? Carfilzomib+Irinotecan
Status: Completed
Location: See all (8) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 1/Phase 2
SUMMARY

The purpose of this study is to determine a well-tolerated dose of Carfilzomib in combination with Irinotecan (Phase 1b portion of the study) 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. \*\*The Phase 1b portion of the study is now complete\*\*. Phase 2 portion of the study. The safest, maximally tolerated dose established as established in Phase 1 for Phase 2 is as follows -- Carfilzomib will be provided at 20/36 mg/m\^2 with Irinotecan dosed at 125 mg/m\^2. The purpose of the Phase 2 portion of the study is to assess 6 month survival of relapsed small cell lung cancer ins subjects treated with this combination therapy.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• Patients must have histologically or cytologically-confirmed diagnosis of progressive or recurrent malignancy as follows:

• 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 Serum Glutamate Oxaloacetic Transaminase (SGOT) and Serum Glutamate Pyruvate Transaminase (SGPT) ≤ 2 x the institutional upper limit of normal all obtained within 14 days prior to enrollment.

• Patients must have an Absolute Neutrophil Count (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:

‣ Phase Ib: 0 or 1

⁃ 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.

Locations
United States
Arizona
Cancer Treatment Centers of America, Western Regional Medical Center
Goodyear
Kentucky
University of Kentucky Markey Cancer Center
Lexington
Norton Cancer Institute
Louisville
Missouri
Washington University School of Medicine
Saint Louis
Oregon
Providence Portland Medical Center | Earle A. Chiles Research Institute
Portland
Texas
University of Texas Medical Branch at Galveston
Galveston
Washington
Virginia Mason Cancer Institute
Seattle
Wisconsin
Aurora Research Institute | Aurora Cancer Care
Wauwatosa
Time Frame
Start Date: 2013-11
Completion Date: 2019-07-01
Participants
Target number of participants: 78
Treatments
Experimental: Phase II
Phase II: Stratified, single arm trial using a starting dose of 20/36 mg/m\^2 of carfilzomib and 125 mg/m\^2 of irinotecan, 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.
Experimental: Phase Ib Cohort 1: 20/27 mg/m^2 Carfilzomib, 125 mg/m^2 Irinotecan
Cohort 1 of Phase Ib run-in to determine maximum tolerated dose (MTD) of Carfilzomib (Day 1,2,8,9, 15, and 16) in combination with Irinotecan (Days 1, 8, 15) in subjects with relapsed small and non-small cell lung cancer or other irinotecan-sensitive cancers.~Cohort 1 used a starting dose of 20/27 mg/m\^2 of carfilzomib in combination with 125 mg/m\^2 of irinotecan.
Experimental: Phase Ib Cohort 2: 20/36 mg/m^2 Carfilzomib, 125 mg/m^2 Irinotecan
Cohort 2 of Phase Ib run-in to determine maximum tolerated dose (MTD) of Carfilzomib (Day 1,2,8,9, 15, and 16) in combination with Irinotecan (Days 1, 8, 15) in subjects with relapsed small and non-small cell lung cancer or other irinotecan-sensitive cancers.~Cohort 2 used a starting dose of 20/36 mg/m\^2 of carfilzomib in combination with 125 mg/m\^2 of irinotecan.
Experimental: Phase Ib Cohort 1: 20/45 mg/m^2 Carfilzomib, 125 mg/m^2 Irinotecan
Cohort 3 of Phase Ib run-in to determine maximum tolerated dose (MTD) of Carfilzomib (Day 1,2,8,9, 15, and 16) in combination with Irinotecan (Days 1, 8, 15) in subjects with relapsed small and non-small cell lung cancer or other irinotecan-sensitive cancers.~Cohort 3 used a starting dose of 20/45 mg/m\^2 of carfilzomib in combination with 125 mg/m\^2 of irinotecan.
Sponsors
Collaborators: Washington University School of Medicine, Lucille P. Markey Cancer Center at University of Kentucky
Leads: Cancer Research and Biostatistics Clinical Trials Consortium

This content was sourced from clinicaltrials.gov

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