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Phase 1b/2, Multicenter Open-label Study of the Safety and Activity of Carfilzomib in Subjects With Relapsed Solid Tumors, Multiple Myeloma or Lymphoma


Phase 1/Phase 2
18 Years
N/A
Open (Enrolling)
Both
Ovarian Cancer, Renal Cancer, Non-small Cell Lung Cancer, Small Cell Lung Cancer, Solid Tumors, Multiple Myeloma, Lymphoma

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Trial Information

Phase 1b/2, Multicenter Open-label Study of the Safety and Activity of Carfilzomib in Subjects With Relapsed Solid Tumors, Multiple Myeloma or Lymphoma


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

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Phase 1b portion will determine the Maximum Tolerated Dose

Outcome Time Frame:

4 to 12 months

Safety Issue:

Yes

Authority:

United States: Food and Drug Administration

Study ID:

PX-171-007

NCT ID:

NCT00531284

Start Date:

September 2007

Completion Date:

June 2014

Related Keywords:

  • Ovarian Cancer
  • Renal Cancer
  • Non-Small Cell Lung Cancer
  • Small Cell Lung Cancer
  • Solid Tumors
  • Multiple Myeloma
  • Lymphoma
  • Non-small cell lung carcinoma
  • Small-cell lung carcinoma
  • Ovarian Cancer
  • Renal Cancer
  • Other solid tumors
  • multiple myeloma
  • lymphoma
  • Carcinoma, Non-Small-Cell Lung
  • Carcinoma, Renal Cell
  • Kidney Neoplasms
  • Lung Neoplasms
  • Lymphoma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Ovarian Neoplasms
  • Small Cell Lung Carcinoma
  • Neoplasms

Name

Location

Hackensack University Medical CenterHackensack, New Jersey  07601
Northwestern UniversityChicago, Illinois  60611
Tower Cancer Research FoundationBeverly Hills, California  90211
University of Maryland Greenebaum Cancer CenterBaltimore, Maryland  21201
The Sarah Cannon Research InstituteNashville, Tennessee  37203
South Texas Accelerated Research Therapeutics (START)San Antonio, Texas  78229
Pinnacle OncologyScottsdale, Arizona  85258