Phase 1b/2 Study of Carfilzomib in Relapsed Solid Tumors and Multiple Myeloma

Official Title: “Phase 1b/2, Multicenter Open-label Study of the Safety and Activity of Carfilzomib in Subjects With Relapsed Solid Tumors and in Multiple Myeloma”

Phase 1b (Bolus and Infusion): To evaluate the safety and tolerability of carfilzomib in subjects with relapsed solid tumors and in subjects with relapsed and/or refractory multiple myeloma

Phase 2 (Bolus and Infusion): To evaluate the overall response rate (ORR) after 4 cycles of carfilzomib in subjects with relapsed solid tumors and in subjects with newly diagnosed multiple myeloma

Intervention(s) in this Clinical Trial

• Drug: carfilzomib
  • 30 minute IV infusion twice weekly for 3 weeks in a 28-day cycle. A maximum of 12 cycles will be administered.

Primary Measures

• Phase 1b portion will determine the Maximum Tolerated Dose); Phase 2 portion will evaluate Overall Response Rate
  • Time Frame: 4 to 12 months
    Safety Issue?: Yes

Inclusion Criteria:

• Disease related

Phase 1 Subjects (Bolus and Infusion):

Solid Tumor:

• Histologically confirmed advanced solid tumor
• 1 to 3 prior treatment regimens
• At least one site of radiographically measurable disease of ≥ 2 cm in the largest dimension by traditional computerized tomography (CT) scanning technique or ≥ 1 cm in the largest dimension by spiral CT scanning (per RECIST criteria); or if, in the Principal Investigator's opinion, evaluable disease can be reliably and consistently followed, the subject may be eligible upon approval by the Proteolix, Inc. Medical
• Monitor

Multiple Myeloma:

• Relapsed and/or refractory multiple myeloma following 2 or more prior treatment regimens.
• Measurable disease as indicated by one or more of the following:
• Serum M-protein ≥ 1 g/dL
• Urine M-protein ≥ 200 mg/24 hr
• Serum Free Light Chain: Involved free light chain (FLC) level ≥ 10 mg/dL provided serum FLC ratio is abnormal

Phase 2 Infusion Subjects:

Solid Tumor:

• Histologically confirmed advanced solid tumor diagnosis and:
• Non-small cell lung cancer (NSCLC): Failed at least 1 prior platinum-based chemotherapy regimen but not more than 3 prior therapies for metastatic disease
• Small cell lung cancer (SCLC): Failed 1 to 3 prior chemotherapy regimens
• Renal: Failed at least 2 prior chemotherapy regimens for metastatic disease
• At least one site of radiographically measurable disease of ≥ 2 cm in the largest dimension by traditional CT scanning technique or > 1 cm in the largest dimension by spiral CT scanning (per RECIST criteria); or if, in the Principal Investigator's opinion, evaluable disease can be reliably and consistently followed, the subject may be eligible upon approval by the Proteolix, Inc. Medical Monitor

Multiple Myeloma:

• Newly diagnosed multiple myeloma
• Measurable disease as indicated by one or more of the following:
• Serum M-protein ≥ 1 g/dL
• Urine M-protein ≥ 200 mg/24 hours
• Serum Free Light Chain: Involved FLC level ≥ 10 mg/dL provided serum FLC ratio is abnormal Demographic
• Males and females ≥ 18 years of age
• Life expectancy of more than 3 months
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 Laboratory
• Adequate hepatic function, with bilirubin 1.5 times the upper limit of normal (ULN), and alanine aminotransferase (ALT) 3 times ULN
• Absolute neutrophil count (ANC) > 1000/mm3, hemoglobin ≥ 8 gm/dL for solid tumors or 7.0gm/dL for MM, and platelet count ≥ 100,000/ mm3 for solid tumors or ≥ 30,000/mm3 for MM.
• Subjects should not have received platelet transfusions for at least 1 week prior to screening
• Screening ANC should be independent of granulocyte- and granulocyte/macrophage colony stimulating factor (G-CSF and GM-CSF) support for at least 1 week and of pegylated G CSF for ≥ 2 weeks
• Subjects may receive red blood cell (RBC) transfusions or receive supportive care with erythropoietin or darbepoetin in accordance with institutional guidelines
• Calculated or measured creatinine clearance (CrCl) of ≥ 20 mL/minute calculated using the formula of Cockcroft and Gault [(140 - Age) x Mass (kg) / (72 x Creatinine mg/dL)]. Multiply result by 0.85 if female. Subjects with calculated CrCl < 20 mL/min may be allowed, only with prior approval by the Proteolix Medical Monitor.
• Ethical/Other
• Written informed consent in accordance with federal, local, and institutional guidelines
• Female subjects of childbearing potential must have a negative serum or urine pregnancy test within 3 days of the first dose and agree to use dual methods of contraception during the study and for 3 months following the last dose of study drug. Post-menopausal females (>45 years old and without menses for > 1 year) and surgically sterilized females are exempt from these requirements. Male subjects must use an effective barrier method of contraception during the study and for 3 months following the last dose if sexually active with a female of childbearing potential.

Exclusion Criteria:

• Disease Related
• Chemotherapy with approved or investigational anticancer therapeutics, including steroid therapy, within 3 weeks prior to first dose or 6 weeks for antibody therapy
• Radiation therapy or immunotherapy within 3 weeks prior to first dose (except for antibody therapy, where 6 weeks is required); localized radiation therapy within 1 week prior to first dose
• Subjects with prior brain metastases are permitted, but must have completed treatment and have no evidence of active central nervous system (CNS) disease for at least 4 weeks prior to first dose
• Participation in an investigational therapeutic study within 3 weeks prior to first dose
• Prior treatment with carfilzomib Concurrent Conditions
• Major surgery within 3 weeks prior to first dose
• Congestive heart failure (New York Heart Association class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, or myocardial infarction within 3 months prior to first dose
• Acute active infection requiring systemic antibiotics, antivirals, or antifungals within 2 weeks prior to first dose
• Known or suspected HIV infection or subjects who are HIV seropositive
• Active hepatitis A, B, or C infection
• Significant neuropathy (Grade 3, Grade 4, or Grade 2 with pain) at the time of the first dose
• Subjects with pleural effusions requiring routine thoracentesis or ascites requiring routine paracentesis
• Subjects at risk* in whom the required program of oral and intravenous fluid hydration is contraindicated, e.g., due to pre-existing pulmonary, cardiac, or renal impairment
• High risk for Tumor Lysis Syndrome. Ethical / Other
• Female subjects who are pregnant or lactating
• Any clinically significant psychiatric or medical condition that in the opinion of the Investigator could interfere with protocol adherence or a subject's ability to give informed consent

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Onyx Therapeutics, Inc. Industry

Overall Clinical Trial Officials and Contacts

Alvin Wong, PharmD Study Director Onyx Therapeutics, Inc.  

Overall Contact: Onyx Therapeutics 877-669-9121 medinfo@onyx-pharm.com

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00531284

Study ID Number: PX-171-007

ClinicalTrials.gov Identifier: NCT00531284

Health Authority: United States: Food and Drug Administration