Study of Carfilzomib With Irinotecan in Irinotecan-Sensitive Malignancies and Small Cell Lung Cancer Patients

NCT01941316 | Completed Phase 1 Results

• 2 other identifiers: CRAB CTC 11-001CAR-IST-553
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 8

Brief 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.

Conditions

Small Cell Lung Carcinoma; Non Small Cell Lung Carcinoma; Irinotecan Sensitive Cancers

Keywords

Carfilzomib; Irinotecan; Small Cell Lung Cancer; Non Small Cell Lung Cancer; Ovarian Cancer; Gastric Cancer; Esophageal Cancer; Cervical Cancer

Outcome Measures

Primary Outcomes (2)

• Phase Ib: Maximum Tolerated Dose

  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.

  28 Days

• Phase II: Overall Survival Rate at 6 Months

  Estimate of 6-month overall survival (OS) rate of relapsed small cell lung cancer patients treated with Carfilzomib in combination with Irinotecan. The survival function was estimated using the Kaplan-Meier method, with overall survival defined as time from enrollment until death. Patients with no date of death were censored at the time of last contact.

  up to 6 Months

Secondary Outcomes (3)

• Overall Response Rate

  From enrollment until the earliest out of date of discontinuation from study or death

• Phase II: Progression-Free Survival Rate at 6 Months

  up to 6 months

• Phase Ib: Dose Limiting Toxicities

  up to 6 months

Study Arms (4)

Phase II

EXPERIMENTAL

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.

Drug: Carfilzomib; Drug: Irinotecan

Phase Ib Cohort 1: 20/27 mg/m^2 Carfilzomib, 125 mg/m^2 Irinotecan

EXPERIMENTAL

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.

Drug: Carfilzomib; Drug: Irinotecan

Phase Ib Cohort 2: 20/36 mg/m^2 Carfilzomib, 125 mg/m^2 Irinotecan

EXPERIMENTAL

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.

Drug: Carfilzomib; Drug: Irinotecan

Phase Ib Cohort 1: 20/45 mg/m^2 Carfilzomib, 125 mg/m^2 Irinotecan

EXPERIMENTAL

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.

Drug: Carfilzomib; Drug: Irinotecan

Interventions

Carfilzomib DRUG

20/36 \* mg/m\^2 stepped up dosing, 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.

Also known as: Kyprolis

Phase II; Phase Ib Cohort 1: 20/27 mg/m^2 Carfilzomib, 125 mg/m^2 Irinotecan; Phase Ib Cohort 1: 20/45 mg/m^2 Carfilzomib, 125 mg/m^2 Irinotecan; Phase Ib Cohort 2: 20/36 mg/m^2 Carfilzomib, 125 mg/m^2 Irinotecan

Irinotecan DRUG

125 mg/m\^2, 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.

Also known as: Camptosar, Campto

Phase II; Phase Ib Cohort 1: 20/27 mg/m^2 Carfilzomib, 125 mg/m^2 Irinotecan; Phase Ib Cohort 1: 20/45 mg/m^2 Carfilzomib, 125 mg/m^2 Irinotecan; Phase Ib Cohort 2: 20/36 mg/m^2 Carfilzomib, 125 mg/m^2 Irinotecan

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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, New York Heart Association (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.

Sponsors & Collaborators

• Cancer Research and Biostatistics Clinical Trials Consortium: lead
• Lucille P. Markey Cancer Center at University of Kentucky: collaborator
• Washington University School of Medicine: collaborator

Study Sites (8)

Cancer Treatment Centers of America, Western Regional Medical Center

Goodyear, Arizona, 85338, United States

Location

University of Kentucky Markey Cancer Center

Lexington, Kentucky, 40536, United States

Location

Norton Cancer Institute

Louisville, Kentucky, 40202, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Providence Portland Medical Center | Earle A. Chiles Research Institute

Portland, Oregon, 97213, United States

Location

University of Texas Medical Branch at Galveston

Galveston, Texas, 77555, United States

Location

Virginia Mason Cancer Institute

Seattle, Washington, 98111, United States

Location

Aurora Research Institute | Aurora Cancer Care

Wauwatosa, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Small Cell Lung Carcinoma; Carcinoma, Non-Small-Cell Lung; Ovarian Neoplasms; Stomach Neoplasms; Esophageal Neoplasms; Uterine Cervical Neoplasms

Interventions

carfilzomib; Irinotecan

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Head and Neck Neoplasms; Esophageal Diseases; Uterine Neoplasms; Uterine Cervical Diseases; Uterine Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds

Results Point of Contact

• Title: Director of Quality and Regulatory Compliance
• Organization: Cancer Research and Biostatistics

lisau@crab.org

206-839-1782

Study Officials

• Susanne M Arnold, MD

  Lucille P. Markey Cancer Center at University of Kentucky

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: A total of 16 patients were enrolled to the Phase 1b run-in at 3 different dosing levels: 4 patients into Dosing Level 1: 20/27 mg/m\^2 Carfilzomib, 125 mg/m\^2 Irinotecan 9 patients into Dosing Level 2: 20/27 mg/m\^2 Carfilzomib, 125 mg/m\^2 Irinotecan 3 patients into Dosing Level 3: 20/27 mg/m\^2 Carfilzomib, 125 mg/m\^2 Irinotecan A total of 62 patients were enrolled into the Phase 2 trial. The Phase 2 component is a single-arm component, with participants stratified into two groups: 37 platinum-sensitive 25 platinum-refractory Enrollment was not sequential, as all participants in the Phase 2 component were different individuals than the participants enrolled into the Phase 1b component.

Study Record Dates

• First Submitted: August 19, 2013
• First Posted: September 13, 2013
• Study Start: November 1, 2013
• Primary Completion: December 31, 2018
• Study Completion: July 1, 2019
• Last Updated: May 9, 2024
• Results First Posted: May 9, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)