Small Cell Lung CarcinomaPhase 1/2NCT01941316
Study of Carfilzomib With Irinotecan in Irinotecan-Sensitive Malignancies and Small Cell Lung Cancer Patients
A Phase 1/2 study testing Carfilzomib and Irinotecan in people with Small Cell Lung Carcinoma and Non Small Cell Lung Carcinoma, run by Cancer Research and Biostatistics Clinical Trials Consortium at 8 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Small Cell Lung Carcinoma, Non Small Cell Lung Carcinoma, Irinotecan Sensitive Cancers
- What is being tested?
- Carfilzomib and Irinotecan
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 78 participants
- Where
- 8 sitesUnited States
- Study dates
- Nov 2013to 1 Jul 2019
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
- 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.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
University of Texas Medical Branch at Galveston
Galveston, Texas, 77555
Cancer Treatment Centers of America, Western Regional Medical Center
Goodyear, Arizona, 85338
University of Kentucky Markey Cancer Center
Lexington, Kentucky, 40536
Norton Cancer Institute
Louisville, Kentucky, 40202
Providence Portland Medical Center | Earle A. Chiles Research Institute
Portland, Oregon, 97213
Virginia Mason Cancer Institute
Seattle, Washington, 98111
Washington University School of Medicine
St Louis, Missouri, 63110
Aurora Research Institute | Aurora Cancer Care
Wauwatosa, Wisconsin, 53226
About this study
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
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.
Read the detailed description
Small cell lung cancer accounts for approximately 15% of all lung cancer diagnoses in the United States (US), with 60-80% response rates to platinum-based chemotherapy in extensive disease. Despite its sensitivity to chemotherapy, small cell lung cancer is characterized by its tendency to spread to other locations in the body such as the bloodstream and other organs such as the liver. Currently, the only FDA-approved second-line therapies are oral and parenteral topotecan, although irinotecan is also commonly used in primary and relapsed disease. Novel combination therapies are desperately needed in this disease. in order to improve survival.
Carfilzomib (also known as Kyprolis) is an anti-cancer drug classified as a selective proteasome inhibitor. Proteasome inhibition affects the levels of numerous cell cycle control proteins, apoptosis (i.e., cell death), cell adhesion, angiogenesis, and chemoresistance proteins. Chemically, it is similar to epoxomicin.
Carfilzomib and other proteasome inhibitors interrupt cellular pathways integral to the survival of small cell lung cancer, namely the apoptotic pathway involving activated Nuclear Factor-kB (referenced as NF-kB). NF-kB activates the transcription of anti-apoptotic and proliferation genes, mediating tumor cell survival in response to cytotoxic stress thus resulting in chemoresistance, a common problem in small cell lung cancer. Carfilzomib prevents the breakdown of IkappaB (referenced as IkB), a protein which inhibits NF-kB, controls levels of the anti-apoptotic gene Bcl-2 and the tumor suppressor p53. Overexpression of Bcl-2, a key mediator of resistance to apoptosis following chemotherapy, which is an important problem in small cell lung cancer.
In this trial, Carfilzomib is combined with Irinotecan. Irinotecan, a camptothecins, inhibits topoisomerase I, thought to be important in the growth and spread of cancer. As a class, camptothecins have shown efficacy in small cell lung cancer in a variety of settings.
Topoisomerase-1 is thought to cause apoptosis via mechanisms other than NF-kB, adding to the potential synergy of these compounds. In addition, topoisomerase-1 is overexpressed in the majority of subjects with small cell lung cancer and decreased degradation of this enzyme is expected to lead to further enhancement of this mechanism of apoptosis
The pivotal phase III study which led to FDA approval of topotecan in relapsed small cell lung cancer was by Von Pawel et al, and included 211 subjects with sensitive (> 60 days since prior therapy) relapse and randomized them to either topotecan (107 subjects) daily for 5 days or to cyclophosphamide, doxorubicin, and vincristine (CAV), each given every 21 days. Topotecan showed no significant improvement in the median time to progression (13.3 weeks vs.12.3 weeks, p=0.552) or median survival (25 weeks vs. 24.7 weeks, p=0.795), however, subjects treated with topotecan had improvement in cancer-related symptoms (dyspnea, hoarseness, anorexia, and fatigue) as well as hematologic toxicity. Irinotecan, has established activity in small cell lung cancer, as well as non-small cell lung cancer, colorectal cancer and ovarian cancer.
In this Phase 2 study patients will be treated with the Maximum Tolerated Dose (MTD) of Carfilzomib 20/36 mg/m^2 as stepped up dosing determined in Phase 1b and 125mg/m^2 of Irinotecan.
- Being tested
- Carfilzomib, Irinotecan
- Keywords
- Carfilzomib, Irinotecan, Small Cell Lung Cancer, Non Small Cell Lung Cancer, Ovarian Cancer, Gastric Cancer, Esophageal Cancer, Cervical Cancer
- Medical subject headings
- Small Cell Lung Carcinoma, Carcinoma, Non-Small-Cell Lung, Ovarian Neoplasms, Stomach Neoplasms, Esophageal Neoplasms, Uterine Cervical Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarfilzomibDrug
Also called Kyprolis
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.
IrinotecanDrug
Also called Camptosar, Campto
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Carfilzomib; Drug: Irinotecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: up to 6 Months
Secondary outcomes (3)
Overall Response Rate
Rate of overall response of relapsed small cell lung cancer patients treated with Carfilzomib in combination with Irinotecan.
Responses were evaluated by the criteria defined in RECIST v1.1. Patients were categorized at each response assessment as having one of the following:
complete response (CR) partial response (PR) stable disease (SD) progressive disease (PD) not assessable (NA)
Overall response rate is defined as the proportion of patients achieving a best response of PR or better while on study; in other words, the proportion of patients achieving a CR or PR while on study.
Measured: From enrollment until the earliest out of date of discontinuation from study or death
Phase II: Progression-Free Survival Rate at 6 Months
Estimate of 6-month progression-free survival (PFS) 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 progression-free survival defined as time from enrollment until disease progression or death. Patients with no date of death and no date of disease progression were censored at the time of last contact.
Measured: up to 6 months
Phase Ib: Dose Limiting Toxicities
Number of Dose Limiting Toxicity (DLT) adverse events related to Carfilzomib in combination with Irinotecan administration. Subjects were 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
Measured: up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2013 (estimated)
- Study startNov 2013
- Primary completion31 Dec 2018
- Study completion1 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Small Cell Lung CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 78 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cancer Research and Biostatistics Clinical Trials Consortium
- Sponsor type
- Research network
- Collaborators
- Lucille P. Markey Cancer Center at University of Kentucky, Washington University School of Medicine
- Responsible party
- Sponsor
- Investigators
- Susanne M Arnold, MD, Principal investigator, Lucille P. Markey Cancer Center at University of Kentucky
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01941316
- Sponsor's protocol ID
- CRAB CTC 11-001
- Other IDs
- CAR-IST-553
- Status last verified
- Apr 2024
- First submitted
- 19 Aug 2013
- Last updated
- 9 May 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01941316
- Acronym / sponsor ID
- CRAB CTC 11-001
- Keywords
- Carfilzomib, Irinotecan, Small Cell Lung Cancer, Non Small Cell Lung Cancer, Ovarian Cancer, Gastric Cancer, Esophageal Cancer, Cervical Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 78 participants (actual)
- Lead sponsor
- Cancer Research and Biostatistics Clinical Trials ConsortiumResearch network
- Collaborators
- Lucille P. Markey Cancer Center at University of Kentucky, Washington University School of Medicine
- Study start
- Nov 2013
- Primary completion
- 31 Dec 2018 (actual)
- Study completion
- 1 Jul 2019 (actual)
- First posted
- 13 Sep 2013 (estimated)
- Results
- Posted 9 May 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Small cell lung cancer accounts for approximately 15% of all lung cancer diagnoses in the United States (US), with 60-80% response rates to platinum-based chemotherapy in extensive disease. Despite its sensitivity to chemotherapy, small cell lung cancer is characterized by its tendency to spread to other locations in the body such as the bloodstream and other organs such as the liver. Currently, the only FDA-approved second-line therapies are oral and parenteral topotecan, although irinotecan is also commonly used in primary and relapsed disease. Novel combination therapies are desperately needed in this disease. in order to improve survival.
Carfilzomib (also known as Kyprolis) is an anti-cancer drug classified as a selective proteasome inhibitor. Proteasome inhibition affects the levels of numerous cell cycle control proteins, apoptosis (i.e., cell death), cell adhesion, angiogenesis, and chemoresistance proteins. Chemically, it is similar to epoxomicin.
Carfilzomib and other proteasome inhibitors interrupt cellular pathways integral to the survival of small cell lung cancer, namely the apoptotic pathway involving activated Nuclear Factor-kB (referenced as NF-kB). NF-kB activates the transcription of anti-apoptotic and proliferation genes, mediating tumor cell survival in response to cytotoxic stress thus resulting in chemoresistance, a common problem in small cell lung cancer. Carfilzomib prevents the breakdown of IkappaB (referenced as IkB), a protein which inhibits NF-kB, controls levels of the anti-apoptotic gene Bcl-2 and the tumor suppressor p53. Overexpression of Bcl-2, a key mediator of resistance to apoptosis following chemotherapy, which is an important problem in small cell lung cancer.
In this trial, Carfilzomib is combined with Irinotecan. Irinotecan, a camptothecins, inhibits topoisomerase I, thought to be important in the growth and spread of cancer. As a class, camptothecins have shown efficacy in small cell lung cancer in a variety of settings.
Topoisomerase-1 is thought to cause apoptosis via mechanisms other than NF-kB, adding to the potential synergy of these compounds. In addition, topoisomerase-1 is overexpressed in the majority of subjects with small cell lung cancer and decreased degradation of this enzyme is expected to lead to further enhancement of this mechanism of apoptosis
The pivotal phase III study which led to FDA approval of topotecan in relapsed small cell lung cancer was by Von Pawel et al, and included 211 subjects with sensitive (> 60 days since prior therapy) relapse and randomized them to either topotecan (107 subjects) daily for 5 days or to cyclophosphamide, doxorubicin, and vincristine (CAV), each given every 21 days. Topotecan showed no significant improvement in the median time to progression (13.3 weeks vs.12.3 weeks, p=0.552) or median survival (25 weeks vs. 24.7 weeks, p=0.795), however, subjects treated with topotecan had improvement in cancer-related symptoms (dyspnea, hoarseness, anorexia, and fatigue) as well as hematologic toxicity. Irinotecan, has established activity in small cell lung cancer, as well as non-small cell lung cancer, colorectal cancer and ovarian cancer.
In this Phase 2 study patients will be treated with the Maximum Tolerated Dose (MTD) of Carfilzomib 20/36 mg/m^2 as stepped up dosing determined in Phase 1b and 125mg/m^2 of Irinotecan.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Phase II | Experimental | Drug: Carfilzomib, Drug: IrinotecanPhase 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. |
| Phase Ib Cohort 1: 20/27 mg/m^2 Carfilzomib, 125 mg/m^2 Irinotecan | Experimental | Drug: Carfilzomib, Drug: IrinotecanCohort 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. |
| Phase Ib Cohort 2: 20/36 mg/m^2 Carfilzomib, 125 mg/m^2 Irinotecan | Experimental | Drug: Carfilzomib, Drug: IrinotecanCohort 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. |
| Phase Ib Cohort 1: 20/45 mg/m^2 Carfilzomib, 125 mg/m^2 Irinotecan | Experimental | Drug: Carfilzomib, Drug: IrinotecanCohort 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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.
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CarfilzomibAlso: Kyprolis20/36 * 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. | Drug | 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 |
| IrinotecanAlso: Camptosar, Campto125 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. | Drug | 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 |
Primary outcome
Phase Ib: Maximum Tolerated Dose
Time frame: 28 Days
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.
Phase II: Overall Survival Rate at 6 Months
Time frame: up to 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.
3 secondary outcomes
Overall Response Rate
Time frame: From enrollment until the earliest out of date of discontinuation from study or death
Phase II: Progression-Free Survival Rate at 6 Months
Time frame: up to 6 months
Phase Ib: Dose Limiting Toxicities
Time frame: up to 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Susanne M Arnold, MD principal investigator
Lucille P. Markey Cancer Center at University of Kentucky
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Carfilzomib and Irinotecan in people with Small Cell Lung Carcinoma and Non Small Cell Lung Carcinoma, run by Cancer Research and Biostatistics Clinical Trials Consortium at 8 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase Ib: Maximum Tolerated Dose (time frame: 28 Days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 May 2024.