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

NCT02447887 | Terminated Phase 1 Results DMC

• 2 other identifiers: GU-07114-052
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

Metastatic Renal Cell Carcinoma; RCC

Outcome Measures

Primary Outcomes (8)

• Non-hematologic Toxicity ≥ Grade 3 Per CTCAE v4 Except:

  * 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.

  Up to week 8

• Thrombocytopenia ≥ Grade 3 Per CTCAE v4

  Up to week 8

• Grade 4 Neutropenia Per CTCAE v4; Associated With Fever or Hospitalization for Infection

  Up to week 8

• Grade 4 Neutropenia Per CTCAE v4; Lasting Longer Than 5 Days

  Up to week 8

• 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.

  28 Days

• 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.

  28 Days

• Progression Free Survival Per RECIST 1.1

  At week 8

• Progression Free Survuval Per RECIST 1.1

  At week 16

Secondary Outcomes (2)

• Overall Response Rate

  Week 8

• Overall Response Rate

  Week 16

Study Arms (1)

Ixazomib and pegylated IFN alfa - 2b

EXPERIMENTAL

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; Drug: Pegylated IFN-alpha 2b

Interventions

Ixazomib DRUG

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).

Ixazomib and pegylated IFN alfa - 2b

Pegylated IFN-alpha 2b DRUG

Weekly injection

Also known as: pIFN - alpha 2b

Ixazomib and pegylated IFN alfa - 2b

Eligibility Criteria

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

You may qualify if:

• Male or female patients 18 years or older.
• 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.
• 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.)
• 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.)
• Patients must have a diagnosis of a metastatic renal cell carcinoma with a ≥50% clear cell component.
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2.
• 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).

You may not qualify if:

• Female patients who are lactating or have a positive serum pregnancy test during the screening period.
• Failure to have fully recovered (ie, ≤ Grade 1 toxicity) from the reversible effects of prior chemotherapy, radiation therapy or targeted therapy
• Previous use of interferon, ixazomib or bortezomib.
• 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
• Major surgery within 14 days before enrollment.
• 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.
• Untreated central nervous system involvement.
• Uncontrolled thyroid disease.
• Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment.
• 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.
• 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.
• Known ongoing or active systemic infection, active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive.

Sponsors & Collaborators

• Fox Chase Cancer Center: lead

Study Sites (1)

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

ixazomib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Dr. Daniel M. Geynisman
• Organization: Fox Chase Cancer Center

daniel.geynisman@fccc.edu

215-728-3889

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2015
• First Posted: May 19, 2015
• Study Start: August 14, 2015
• Primary Completion: April 25, 2017
• Study Completion: April 25, 2017
• Last Updated: September 26, 2019
• Results First Posted: September 26, 2019

Record last verified: 2019-09

Locations

US (1)