Trial record 10 of 74 for:    "Kidney Neoplasms" AND (woman OR women OR female)

Phase 1b/2 Study of Carfilzomib in Relapsed Solid Tumors, Multiple Myeloma, or Lymphoma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Onyx Pharmaceuticals ( Onyx Therapeutics, Inc. )
ClinicalTrials.gov Identifier:
NCT00531284
First received: September 14, 2007
Last updated: December 6, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Ovarian Cancer
Renal Cancer
Non-small Cell Lung Cancer
Small Cell Lung Cancer
Solid Tumors
Multiple Myeloma
Lymphoma
Drug: Carfilzomib 30 min IV infusion
Drug: Carfilzomib bolus administration up to 10 min
Drug: Carfizomib 30 min infusion plus 40 mg/week dexamethasone
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Onyx Pharmaceuticals:

Primary Outcome Measures:
  • Phase 1b portion will determine the Maximum Tolerated Dose [ Time Frame: 4 to 12 months ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 235
Study Start Date: September 2007
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Solid Tumor

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.
Drug: Carfilzomib 30 min IV infusion
30 minute IV infusion twice weekly for 3 weeks in a 28-day cycle.
Drug: Carfilzomib bolus administration up to 10 min
Bolus administration over a period of up to 10 minutes.
Experimental: Multiple Myeloma

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.
Drug: Carfilzomib 30 min IV infusion
30 minute IV infusion twice weekly for 3 weeks in a 28-day cycle.
Drug: Carfizomib 30 min infusion plus 40 mg/week dexamethasone
30 minute IV infusion plus 40 mg/week of dexamethasone
Experimental: Lymphoma

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.
Drug: Carfilzomib 30 min IV infusion
30 minute IV infusion twice weekly for 3 weeks in a 28-day cycle.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00531284

Locations
United States, Arizona
Pinnacle Oncology
Scottsdale, Arizona, United States, 85258
United States, California
Tower Cancer Research Foundation
Beverly Hills, California, United States, 90210
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
United States, Maryland
University of Maryland Greenebaum Cancer Center
Baltimore, Maryland, United States, 21201
United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
United States, Tennessee
The Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203-1632
United States, Texas
South Texas Accelerated Research Therapeutics (START)
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Onyx Therapeutics, Inc.
Investigators
Study Director: Naseem Zojwalla Onyx Pharmaceuticals
  More Information

No publications provided by Onyx Pharmaceuticals

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Onyx Pharmaceuticals ( Onyx Therapeutics, Inc. )
ClinicalTrials.gov Identifier: NCT00531284     History of Changes
Other Study ID Numbers: PX-171-007
Study First Received: September 14, 2007
Last Updated: December 6, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Onyx Pharmaceuticals:
Non-small cell lung carcinoma
Small-cell lung carcinoma
Ovarian Cancer
Renal Cancer
Other solid tumors
multiple myeloma
lymphoma

Additional relevant MeSH terms:
Kidney Neoplasms
Genital Diseases, Female
Genital Neoplasms, Female
Carcinoma, Non-Small-Cell Lung
Carcinoma, Renal Cell
Lung Neoplasms
Lymphoma
Multiple Myeloma
Neoplasms, Plasma Cell
Ovarian Neoplasms
Small Cell Lung Carcinoma
Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Urologic Neoplasms
Urogenital Neoplasms
Kidney Diseases
Urologic Diseases
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders

ClinicalTrials.gov processed this record on July 28, 2014