Phase 1b/2 Study of Carfilzomib in Relapsed Solid Tumors, Multiple Myeloma, or Lymphoma
This trial is active, not recruiting.
|Conditions||ovarian cancer, renal cancer, non-small cell lung cancer, small cell lung cancer, solid tumors, multiple myeloma, lymphoma|
|Treatments||carfilzomib 30 min iv infusion, carfilzomib bolus administration up to 10 min, carfizomib 30 min infusion plus 40 mg/week dexamethasone|
|Phase||phase 1/phase 2|
|Sponsor||Onyx Therapeutics, Inc.|
|Start date||September 2007|
|End date||July 2014|
|Trial size||184 participants|
|Trial identifier||NCT00531284, PX-171-007|
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 and in subjects with refractory lymphoma.
Phase 2 (Bolus and Infusion): To evaluate the overall response rate (ORR) after 4 cycles of carfilzomib in subjects with relapsed solid tumors.
|United States||No locations recruiting|
|Other countries||No locations recruiting|
|Scottsdale, AZ||Pinnacle Oncology||no longer recruiting|
|Beverly Hills, CA||Tower Cancer Research Foundation||no longer recruiting|
|Chicago, IL||Northwestern University||no longer recruiting|
|Baltimore, MD||University of Maryland Greenebaum Cancer Center||no longer recruiting|
|Hackensack, NJ||Hackensack University Medical Center||no longer recruiting|
|Nashville, TN||The Sarah Cannon Research Institute||no longer recruiting|
|San Antonio, TX||South Texas Accelerated Research Therapeutics (START)||no longer recruiting|
|Endpoint classification||safety/efficacy study|
|Intervention model||parallel assignment|
Phase 1b portion will determine the Maximum Tolerated Dose
time frame: 4 to 12 months
Phase 2 portion will evaluate Overall Response Rate (ORR) after 4 cycles of carfilzomib for subjects with relapsed solid tumors
time frame: 4 to 12 months
Male or female participants at least 18 years old.
- 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 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 Lymphoma:
- Histologically or cytologically confirmed lymphoma.
- Patients must have had an initial diagnosis of indolent NHL (including follicular, small lymphocytic, lymphoplasmacytoid, and marginal zone lymphoma), indolent disease that transformed to a more aggressive subtype, as previously described or patients may have mantle cell lymphoma.
- Patients are required to have received prior rituximab (alone or combined with other treatment) and are considered refractory to (defined as no response, or progression within 6 months of completing therapy) or intolerant of continued rituximab.
- Patients may have received up to a maximum of four prior unique chemotherapy regimens, including if not contra-indicated autologous stem-cell transplantation (ASCT).
- For patients to enroll in the expanded dose group for lymphoma, patients must have measurable disease Phase 2 Bolus Subjects: -Histologically confirmed advanced solid tumor diagnosis and:
- NSCLC: Failed at least 1 prior platinum-based chemotherapy regimen but not more than 3 prior therapies for metastatic disease
- SCLC: Failed 1 to 3 prior chemotherapy regimens
- Ovarian: Failed at least 1 prior platinum-based chemotherapy regimen but not more than 4 therapies for metastatic disease
- Renal: Failed at least 2 prior chemotherapy regimens for metastatic disease
- Other solid tumor types: Failed at least 1 prior chemotherapy regimen for metastatic or relapsed disease and for which standard of care therapy is no longer effective or does not exist
- 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 Medical Monitor 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 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.
- 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
- For lymphoma patients; patients with prior stem cell transplant therapy (autologous SCT within the prior 8 weeks; allogeneic SCT within the prior 16 weeks). Patients with prior allogeneic SCT should not have evidence of moderate-to-severe GvHD (as defined in Filipovich et al 2005).
- Evidence of CNS lymphoma
- 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
|Official title||Phase 1b/2, Multicenter Open-label Study of the Safety and Activity of Carfilzomib in Subjects With Relapsed Solid Tumors, Multiple Myeloma or Lymphoma|
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