Extended Infusion Carfilzomib on a Weekly Schedule in Patients With Advanced Solid Tumors

NCT02257476 | Completed Phase 1 DMC

• 2 other identifiers: IRB00071307WINSHIP2598-13
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to find the safest dose level of an approved drug, carfilzomib, in solid tumors when given over a different period of time than normally used. The study will also use markers in blood from routine blood draws to help check the levels of the drug. Lastly, the study will check how well this drug works with regards to keeping cancer cells from growing with the new time frame of delivery.

Conditions

Neoplasms; Malignancies

Keywords

carfilzomib; advanced solid malignancies; advanced solid cancers; prostate; bladder; colon; breast; lung

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of a weekly 4-hour carfilzomib infusion in patients with advanced solid malignancies

  Evaluate safety and tolerability of weekly dosed carfilzomib as assessed by using NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v.4 criteria to determine DLTs, the MTD, and RP2D

  Up to 18 months

Secondary Outcomes (6)

• Pharmacokinetics (PK) of escalating doses of weekly intravenous carfilzomib

  1, 2, 4, 6, 8, 28 hours post-dose

• Changes in pharmacodynamic (PD) biomarkers before and during treatment with carfilzomib using peripheral blood mononuclear cells (PBMC) and paired tumor biopsies

  Days 1, 2, 3, 8, 15, 21

• Preliminary anti-tumor efficacy (objective response rate)

  Up to 18 months

• Preliminary anti-tumor efficacy (clinical benefit rate)

  Up to 18 months

• Preliminary anti-tumor efficacy (progression free survival)

  Up to 18 months

Study Arms (1)

Carfilzomib

EXPERIMENTAL

Patients will receive single agent carfilzomib on a weekly dosing schedule (days 1, 8, 15) in a 21 day cycle. The initial dose will be 20 mg/m² for cycle 1, day 1. Dose escalation will proceed in a standard 3+3 fashion with the requirement that dose escalation to the next level can only proceed if 0 of 3 or ≤ 1 of 6 patients experience a dose limiting toxicity (DLT). Dexamethasone 8 mg PO/IV will be administered prior to all carfilzomib doses.

Drug: Carfilzomib; Drug: Dexamethasone

Interventions

Carfilzomib DRUG

Carfilzomib will be given as an IV infusion over 4 hours. Subjects will remain at the clinic under observation for at least 1 hour following each dose of carfilzomib in Cycle 1 and following the dose on Cycle 2 Day 1. During these observation times, post dose IV hydration may be given at physician's discretion.

Also known as: PR-171, Kyprolis

Carfilzomib

Dexamethasone DRUG

Dexamethasone 8 mg PO/IV will be administered prior to all carfilzomib doses.

Also known as: Decadron

Carfilzomib

Eligibility Criteria

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

You may qualify if:

• Patient aged 18 years or older at the time of enrollment.
• Advanced/metastatic solid tumor refractory to standard therapy.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 - 2.
• Adequate organ function as assessed by the following:
• Bone marrow:
• Hemoglobin greater than or equal to 9.0 g/dL
• Absolute neutrophil count (ANC) greater than or equal to 1,500/mm³
• Platelet count greater than or equal to 100,000/mm³
• Hepatic:
• Total bilirubin less than or equal to 1.5 x ULN
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 3 x ULN
• Prothrombin time (PT)-international normalized ratio (INR)/partial thromboplastin time (PTT) \< 1.5 x ULN except in patients receiving active anticoagulation
• Renal:
• Serum creatinine ≤ 1.5 x upper limit of normal or
• Glomerular filtration rate (GFR) of 50 ml/minute or greater (if elevated serum creatinine level \> 1.5 x ULN)

You may not qualify if:

• Treatment related residual toxicity \> grade 1.
• Prior treatment with a proteasome inhibitor.
• Uncontrolled systemic disease or intercurrent illness.
• Recent history of myocardial infarction (MI) or symptomatic coronary artery disease within the preceding 6 months.
• History of uncontrolled hypertension (systolic \> 150 mmHg or diastolic pressure \> 90 mmHG despite optimal medical management).
• Ejection fraction \< 50%.
• Known and actively treated infection with human immunodeficiency virus (HIV), hepatitis B or C.
• Major surgery or significant traumatic injury within 4 weeks of first study treatment from which the subject has not fully recovered.
• Pregnant or breast feeding women.
• Female patient of child-bearing potential or male patient with partner of child-bearing potential but unable or unwilling to use effective contraception (double barrier such as condoms, contraceptive sponge, diaphragm or vaginal ring with spermicidal jellies or cream; or hormonal method such as oral, parenteral or transdermal hormonal agents for at least three months prior to study drug administration).
• Corticosteroid doses greater than equivalent of prednisone 7.5 mg PO daily.
• Recent therapy with any active anticancer agent within 4 weeks of the 1st dose of the study drugs.
• Any other current malignancy or previous malignancies within 3 years of enrollment except: curatively treated in situ carcinoma of the cervix uteri; localized basal or squamous cell carcinoma of the skin, curatively treated in situ breast carcinoma, and early stage prostate cancer.
• Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib).
• 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

• Emory University: lead
• Amgen: collaborator

Study Sites (1)

Emory University Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

Neoplasms

Interventions

carfilzomib; Dexamethasone; Calcium Dobesilate

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Bradley C. Carthon, MD, PhD

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: September 26, 2014
• First Posted: October 6, 2014
• Study Start: August 1, 2014
• Primary Completion: November 1, 2016
• Study Completion: November 1, 2016
• Last Updated: February 7, 2017

Record last verified: 2017-02

Locations

US (1)