Overview

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

Summary

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

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Drug: Carfilzomib 30 min IV infusion / Carfilzomib bolus administration up to 10 min Phase 1b portion for solid tumor subjects will enroll into sequential cohorts of 3 subjects to establish the MTD of bolus administration of carfilzomib up to 10 minutes. Effective with Amendment 2, subjects will be enrolled into sequential cohorts of 3 subjects to establish the MTD of carfilzomib administered as a 30-min infusion. In the Phase 2 bolus, a Simon 2-stage open-label study of carfilzomib will be conducted. In Stage 1, 14 subjects will be enrolled in each of 5 solid tumor cohorts (non-small cell lung, small cell lung, ovarian, renal, and any other solid tumor type). If the treatment is associated with at least 1 complete response or 1 PR within a selected tumor cohort (NSCLC, SCLC, ovarian, or renal) after 4 cycles, that cohort will be opened to enroll an additional 16 subjects with that tumor type in Stage 2. The "other solid tumor type" cohort will not proceed to Stage 2.
carfilzomib 30 min iv infusion
30 minute IV infusion twice weekly for 3 weeks in a 28-day cycle.
carfilzomib bolus administration up to 10 min
Bolus administration over a period of up to 10 minutes.
(Experimental)
Drug: Carfilzomib 30 min IV infusion / Carfizomib 30 min infusion plus 40 mg/week dexamethasone In the Phase 1b infusion, subjects will be enrolled into sequential cohorts of 3 subjects to establish the MTD of carfilzomib administered as a 30-minute infusion. Once the MTD is established for the MM and lymphoma cohorts, the MTD cohort may be expanded to enroll up to 15 additional subjects evaluable for toxicity to further characterize safety in these tumor types. Effective with initiation of Amendment 4, approximately 20 additional MM subjects will be enrolled to receive carfilzomib using stepped-up dosing (20/45 mg/m2) combined with 40 mg/week of dexamethasone to further explore safety and tolerability of the 20/45 mg/m2 dose and of the combination of carfilzomib with dexamethasone. The sponsor may elect to explore safety and tolerability of either a 20/36 mg/m2 or 20/56 mg/m2 carfilzomib dose combined with 40 mg/week of dexamethasone.
carfilzomib 30 min iv infusion
30 minute IV infusion twice weekly for 3 weeks in a 28-day cycle.
carfizomib 30 min infusion plus 40 mg/week dexamethasone
30 minute IV infusion plus 40 mg/week of dexamethasone
(Experimental)
Drug: Carfilzomib 30 min IV infusion In the Phase 1b infusion, subjects will be enrolled into sequential cohorts of 3 subjects to establish the MTD of carfilzomib administered as a 30-minute infusion. Once the MTD is established for the MM and lymphoma cohorts, the MTD cohort may be expanded to enroll up to 15 additional subjects evaluable for toxicity to further characterize safety in these tumor types.
carfilzomib 30 min iv infusion
30 minute IV infusion twice weekly for 3 weeks in a 28-day cycle.

Primary Outcomes

Measure
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

Eligibility Criteria

Male or female participants at least 18 years old.

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 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. 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 - 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

Additional Information

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
Trial information was received from ClinicalTrials.gov and was last updated in December 2014.
Information provided to ClinicalTrials.gov by Onyx Pharmaceuticals.