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Study of Ixazomib With Pegylated IFN-alpha 2b (pIFN) in Metastatic Renal Cell Carcinoma (mRCC)

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ClinicalTrials.gov Identifier: NCT02447887
Recruitment Status : Terminated (IRB study closure facilitated by Investigator)
First Posted : May 19, 2015
Results First Posted : September 26, 2019
Last Update Posted : September 26, 2019
Sponsor:
Information provided by (Responsible Party):
Fox Chase Cancer Center

Brief Summary:

This is a Phase I/II trial of the combination pegylated IFN-alpha 2b with ixazomib in metastatic renal cell carcinoma (mRCC). Researchers believe that by disabling the protein complex NF-kB, which controls the transfer of genetic information; using the study drug Ixazomib, they can promote necrotic cell death of RCC using interferon alpha - 2b. They hypothesize that the combination of ixazomib with IFN will lead to increased necrotic cell death in RCC tumors and consequent clinical benefit to patients.

Patients will receive ixazomib capsules and pegylated IFN alfa 2b injection in this research study. Treatments will be given weekly and 4 weeks of treatment make up one cycle.


Condition or disease Intervention/treatment Phase
Metastatic Renal Cell Carcinoma RCC Drug: Ixazomib Drug: Pegylated IFN-alpha 2b Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Study of Ixazomib With Pegylated IFN-alpha 2b (pIFN) in Metastatic Renal Cell Carcinoma (mRCC)
Actual Study Start Date : August 14, 2015
Actual Primary Completion Date : April 25, 2017
Actual Study Completion Date : April 25, 2017


Arm Intervention/treatment
Experimental: Ixazomib and pegylated IFN alfa - 2b
Ixazomib capsules and pegylated IFN alfa 2b injections weekly. Ixazomib will be taken for the last 3 weeks of 28 day cycle. Pegylated IFN alfa 2b injection will be administered weekly, each week of the 28 day cycle.
Drug: Ixazomib
The prescribed administration of ixazomib doses in this study is 1.5-4.0 mg ixazomib weekly for 3 out of 4 weeks in each cycle (1 cycle=28 days).

Drug: Pegylated IFN-alpha 2b
Weekly injection
Other Name: pIFN - alpha 2b




Primary Outcome Measures :
  1. Non-hematologic Toxicity ≥ Grade 3 Per CTCAE v4 Except: [ Time Frame: Up to week 8 ]
    • Grade 3 nausea or Grade 3 vomiting ≤ 72 hours that recovers to grade 0-2 with maximal antiemetic therapy.
    • Grade 3 diarrhea that resolves to grade 0-2 with loperamide or diphenoxylate/atropine within 48 hours.
    • Grade 3 hypercholesterolemia, hypertriglyceridemia, hyperglycemia or hypophosphatemia that resolves to grade 0-2 with medical management.
    • Transient electrolyte abnormalities lasting ≤ 1 week.

  2. Thrombocytopenia ≥ Grade 3 Per CTCAE v4 [ Time Frame: Up to week 8 ]
  3. Grade 4 Neutropenia Per CTCAE v4; Associated With Fever or Hospitalization for Infection [ Time Frame: Up to week 8 ]
  4. Grade 4 Neutropenia Per CTCAE v4; Lasting Longer Than 5 Days [ Time Frame: Up to week 8 ]
  5. Any Toxicity Felt at the Investigator's Discretion to be Possibly or Probably Related to Ixazomib That Causes the Patient to Miss More Than 1 Dose of Either Ixazomib or pIFN in the First 28 Days. [ Time Frame: 28 Days ]
  6. Any Unacceptable Toxicity (UT) Defined as Any CTCAE v4 Grade 5 Toxicity, Grade 4 Neuropsychiatric Toxicity or Grade 4 Clinically Significant Non-hematologic Toxicity Thought to be Definitely, Probably or Possibly Related to Study Drug. [ Time Frame: 28 Days ]
  7. Progression Free Survival Per RECIST 1.1 [ Time Frame: At week 8 ]
  8. Progression Free Survuval Per RECIST 1.1 [ Time Frame: At week 16 ]

Secondary Outcome Measures :
  1. Overall Response Rate [ Time Frame: Week 8 ]
  2. Overall Response Rate [ Time Frame: Week 16 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion:

  1. Male or female patients 18 years or older.
  2. Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
  3. Female patients must be:

    • Postmenopausal for at least 1 year before the screening visit, OR
    • Surgically sterile, OR
    • If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of study drug, OR
    • Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.)
  4. Male patients, even if surgically sterilized (ie, status post-vasectomy), must agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, or agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.)
  5. Patients must have a diagnosis of a metastatic renal cell carcinoma with a ≥50% clear cell component.
  6. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2.
  7. Patients must meet the following clinical laboratory criteria:

    • Absolute neutrophil count (ANC) ≥ 1,000/mm3 and platelet count ≥ 75,000/mm3 and hemoglobin ≥ 9 g/dL. Platelet or red cell transfusions to help patients meet eligibility criteria are not allowed within 3 days before study enrollment.
    • Total bilirubin ≤ 1.5 x the upper limit of the normal range (ULN).
    • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN.
    • Calculated by Cockcroft-Gault creatinine clearance ≥ 30 mL/min (see Section 12.2).
  8. Measurable disease by RECIST 1.1.
  9. Receipt of at least two line of prior therapy for metastatic RCC.
  10. Patients with stable brain metastasis are eligible provided they received definitive therapy (EBRT, gamma knife, surgery) no sooner than 14 days prior to registration and are off all steroids.

Exclusion:

Patients meeting any of the following exclusion criteria are not to be enrolled in the study:

  1. Female patients who are lactating or have a positive serum pregnancy test during the screening period.
  2. Failure to have fully recovered (ie, ≤ Grade 1 toxicity) from the reversible effects of prior chemotherapy, radiation therapy or targeted therapy
  3. Previous use of interferon, ixazomib or bortezomib.
  4. Washout periods for prior therapy are as follows

    • Bevacizumab - last dose must be ≥ 6 weeks prior to day 1 of study treatment.
    • Targeted therapy - last dose must be ≥ 5 half-lives prior to initiation of day 1 of study treatment.
    • Other chemotherapy, immunotherapy, or radiotherapy - Last dose must be ≤ 3 weeks prior to day 1 of study treatment
  5. Major surgery within 14 days before enrollment.
  6. Radiotherapy within 14 days before enrollment. If the involved field is small, 7 days will be considered a sufficient interval between treatment and administration of the Ixazomib.
  7. Untreated central nervous system involvement.
  8. Uncontrolled thyroid disease.
  9. Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment.
  10. Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months.
  11. Systemic treatment, within 14 days before the first dose of Ixazomib, with strong inhibitors of CYP1A2 (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of CYP3A (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John's wort.
  12. Known ongoing or active systemic infection, active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive.
  13. Decompensated liver disease (Child-Pugh score >6) or active or past auto-immune hepatitis.
  14. Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol. In particular, a history of a serous psychiatric illness that might be exacerbated by IFN-α-2b; a history of significant or unstable cardiovascular, hepatic or gastrointestinal disease; a history of autoimmune disease of any kind.
  15. Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
  16. Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib including difficulty swallowing.
  17. Evidence of another clinically or radiographically active invasive malignancy OR Diagnosed or treated for another malignancy within 2 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
  18. Patient has ≥ Grade 3 peripheral neuropathy, or Grade 2 peripheral neuropathy with pain on clinical examination during the screening period.
  19. Participation in other clinical trials, including those with other investigational agents not included in this trial, within 30 days of the start of this trial and throughout the duration of this trial.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02447887


Locations
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United States, Pennsylvania
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
Sponsors and Collaborators
Fox Chase Cancer Center
  Study Documents (Full-Text)

Documents provided by Fox Chase Cancer Center:

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Responsible Party: Fox Chase Cancer Center
ClinicalTrials.gov Identifier: NCT02447887     History of Changes
Other Study ID Numbers: GU-071
14-052 ( Other Identifier: Fox Chase Cancer Center )
First Posted: May 19, 2015    Key Record Dates
Results First Posted: September 26, 2019
Last Update Posted: September 26, 2019
Last Verified: September 2019
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Interferon-alpha
Interferon alpha-2
Ixazomib
Glycine
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Glycine Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Antiviral Agents
Anti-Infective Agents
Immunologic Factors