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

NCT00531284 | Completed Phase 1 Results

• 1 other identifier: PX-171-007
• Study Type: interventional
• Target: 184
• Locations: 1 country
• Sites: 7

Brief Summary

The primary objectives of this Phase 1b/2 study were as follows:

• Phase 1b (Bolus and Infusion): To evaluate the safety and tolerability of carfilzomib in patients with relapsed solid tumors and in patients with relapsed and/or refractory multiple myeloma and in patients with refractory lymphoma.
• Phase 2 (Bolus): To evaluate the overall response rate (ORR) after 4 cycles of carfilzomib in patients with relapsed solid tumors.

Conditions

Ovarian Cancer; Renal Cancer; Non-small Cell Lung Cancer; Small Cell Lung Cancer; Solid Tumors; Multiple Myeloma; Lymphoma

Keywords

Non-small cell lung carcinoma; Small-cell lung carcinoma; Ovarian Cancer; Renal Cancer; Other solid tumors; multiple myeloma; lymphoma

Outcome Measures

Primary Outcomes (2)

• Phase 1b: Number of Participants With Dose-limiting Toxicities (DLT)

  Participants were evaluated for dose-limiting toxicities according to the Common Terminology Criteria for Adverse Events (CTCAE) of the National Cancer Institute (NCI) version 3.0. A DLT was defined as treatment-related ≥ Grade 2 neuropathy with pain, ≥ Grade 3 non-hematologic toxicity, Grade 4 neutropenia or thrombocytopenia lasting 7 or more days, or thrombocytopenia with bleeding. The maximum tolerated dose (MTD) for each of the 3 populations (solid tumor, multiple myeloma, and lymphoma) was defined as the dose level at which \< 33% of participants experienced a dose-limiting toxicity during the first 28-day cycle.

  28 days

• Phase 2: Percentage of Participants With an Overall Response After 4 Treatment Cycles

  Overall response is defined as participants with a best overall response of complete response (CR), partial response (PR) or stable disease (SD) after 4 cycles, assessed by the Investigator using tumor measurement and according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR: Disappearance of all target and non-target lesions and no new lesions; PR: Disappearance of all target lesions, persistence of one or more non-target lesion(s) or/and maintenance of tumor marker level above the normal limits and no lesions, or, at least a 30% decrease in the size of target lesions and no progression of existing non-target lesions or any new lesions. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest size since the treatment started, and no progression of existing non-target lesions or any new lesions.

  4 months

Secondary Outcomes (12)

• Percentage of Participants With an Overall Response Throughout the Study

  Tumor assessments occurred at the end of Cycle 2, 4, 6, 9, and 12 and continued every 3 cycles thereafter up to 6 months after last dose. Analysis includes data up to the data cut-off date of 07 October 2014; maximum duration of treatment was 35 months.

• Duration of Response

  Tumor assessments occurred at the end of Cycle 2, 4, 6, 9, and 12 and continued every 3 cycles thereafter up to 6 months after last dose. Analysis includes data up to the data cut-off date of 07 October 2014; maximum duration of treatment was 35 months.

• Progression-Free Survival

  Tumor assessments occurred at the end of Cycle 2, 4, 6, 9, and 12 and continued every 3 cycles thereafter up to 6 months after last dose. Analysis includes data up to the data cut-off date of 07 October 2014; maximum duration of treatment was 35 months.

• Time to Progression

  Tumor assessments occurred at the end of Cycle 2, 4, 6, 9, and 12 and continued every 3 cycles thereafter up to 6 months after last dose. Analysis includes data up to the data cut-off date of 07 October 2014; maximum duration of treatment was 35 months.

• Maximum Observed Plasma Concentration of Carfilzomib

  Cycle 1, Day 1, predose and at 5 minutes and 15 minutes post start of infusion (for 30-minute infusion groups only), and at the end of infusion, 5, 15, and 30 minutes; and 1, 2, and 4 hours after the end of the infusion.

Study Arms (17)

Phase 1B Solid Tumors: Carfilzomib 20 mg/m² Bolus

EXPERIMENTAL

Participants received carfilzomib 20 mg/m² administered by bolus intravenous infusion over 2-10 minutes on Days 1, 2, 8, 9, 15, and 16 of a 28-day cycle. All participants with stable disease or better after 2 cycles could continue treatment until progressive disease or unacceptable toxicity.

Drug: Carfilzomib

Phase 1B Solid Tumors: Carfilzomib 20/27 mg/m² Bolus

EXPERIMENTAL

Participants received carfilzomib 20 mg/m² administered by bolus intravenous infusion over 2-10 minutes on Cycle 1 Days 1 and 2 only, then 27 mg/m² on Days 8, 9, 15 and 16 and thereafter for the remainder of treatment. All participants with stable disease or better after 2 cycles could continue treatment until progressive disease or unacceptable toxicity.

Drug: Carfilzomib

Phase 1B Solid Tumors: Carfilzomib 20/36 mg/m² Bolus

EXPERIMENTAL

Participants received carfilzomib 20 mg/m² administered by bolus intravenous infusion over 2-10 minutes on Cycle 1 Days 1 and 2 only, then 36 mg/m² on Days 8, 9, 15 and 16 and thereafter for the remainder of treatment. All participants with stable disease or better after 2 cycles could continue treatment until progressive disease or unacceptable toxicity.

Drug: Carfilzomib

Phase 2 Solid Tumors: Carfilzomib 20/36 mg/m² Bolus

EXPERIMENTAL

Participants received carfilzomib 20 mg/m² administered by bolus intravenous infusion over 2-10 minutes on Cycle 1 Days 1 and 2 only, then 36 mg/m² on Days 8, 9, 15 and 16 and thereafter for the remainder of treatment. All participants with stable disease or better after 2 cycles could continue treatment until progressive disease or unacceptable toxicity.

Drug: Carfilzomib

Phase 1B Solid Tumors: Carfilzomib 36 mg/m²

EXPERIMENTAL

Participants received carfilzomib 36 mg/m² administered by intravenous infusion over 30 minutes on Days 1, 2, 8, 9, 15, and 16 of a 28-day cycle for at least 2 cycles. All participants with stable disease or better after 2 cycles could continue treatment until progressive disease or unacceptable toxicity.

Drug: Carfilzomib

Phase 1B Solid Tumors: Carfilzomib 45 mg/m²

EXPERIMENTAL

Participants received carfilzomib 45 mg/m² administered by intravenous infusion over 30 minutes on Days 1, 2, 8, 9, 15, and 16 of a 28-day cycle for at least 2 cycles. All participants with stable disease or better after 2 cycles could continue treatment until progressive disease or unacceptable toxicity.

Drug: Carfilzomib

Phase 1B Solid Tumors: Carfilzomib 20/45 mg/m²

EXPERIMENTAL

Participants received carfilzomib 20 mg/m² administered by intravenous infusion over 30 minutes on Cycle 1 Days 1 and 2 only, then 45 mg/m² on Days 8, 9, 15 and 16 and thereafter for the remainder of treatment. All participants with stable disease or better after 2 cycles could continue treatment until progressive disease or unacceptable toxicity.

Drug: Carfilzomib

Phase 1B Solid Tumors: Carfilzomib 20/56 mg/m²

EXPERIMENTAL

Participants received carfilzomib 20 mg/m² administered by intravenous infusion over 30 minutes on Cycle 1 Days 1 and 2 only, then 56 mg/m² on Days 8, 9, 15 and 16 and thereafter for the remainder of treatment. All participants with stable disease or better after 2 cycles could continue treatment until progressive disease or unacceptable toxicity.

Drug: Carfilzomib

Phase 1B Solid Tumors: Carfilzomib 20/70 mg/m²

EXPERIMENTAL

Participants received carfilzomib 20 mg/m² administered by intravenous infusion over 30 minutes on Cycle 1 Days 1 and 2 only, then 70 mg/m² on Days 8, 9, 15 and 16 and thereafter for the remainder of treatment. All participants with stable disease or better after 2 cycles could continue treatment until progressive disease or unacceptable toxicity.

Drug: Carfilzomib

Phase 1b Multiple Myeloma: Carfilzomib 20/36 mg/m²

EXPERIMENTAL

Participants received carfilzomib 20 mg/m² administered by intravenous infusion over 30 minutes on Cycle 1 Days 1 and 2 only, then 36 mg/m² on Days 8, 9, 15 and 16 and thereafter for the remainder of treatment. All participants with stable disease or better after 2 cycles could continue treatment until progressive disease or unacceptable toxicity.

Drug: Carfilzomib

Phase 1b Multiple Myeloma: Carfilzomib 20/45 mg/m²

EXPERIMENTAL

Participants received carfilzomib 20 mg/m² administered by intravenous infusion over 30 minutes on Cycle 1 Days 1 and 2 only, then 45 mg/m² on Days 8, 9, 15 and 16 and thereafter for the remainder of treatment. All participants with stable disease or better after 2 cycles could continue treatment until progressive disease or unacceptable toxicity.

Drug: Carfilzomib

Phase 1b Multiple Myeloma: Carfilzomib 20/56 mg/m²

EXPERIMENTAL

Participants received carfilzomib 20 mg/m² administered by intravenous infusion over 30 minutes on Cycle 1 Days 1 and 2 only, then 56 mg/m² on Days 8, 9, 15 and 16 and thereafter for the remainder of treatment. All participants with stable disease or better after 2 cycles could continue treatment until progressive disease or unacceptable toxicity.

Drug: Carfilzomib

Phase 1b Multiple Myeloma: Carfilzomib 20/70 mg/m²

EXPERIMENTAL

Participants received carfilzomib 20 mg/m² administered by intravenous infusion over 30 minutes on Cycle 1 Days 1 and 2 only, then 70 mg/m² on Days 8, 9, 15 and 16 and thereafter for the remainder of treatment. All participants with stable disease or better after 2 cycles could continue treatment until progressive disease or unacceptable toxicity.

Drug: Carfilzomib

Phase 1b Lymphoma: Carfilzomib 20/56 mg/m²

EXPERIMENTAL

Participants received carfilzomib 20 mg/m² administered by intravenous infusion over 30 minutes on Cycle 1 Days 1 and 2 only, then 56 mg/m² on Days 8, 9, 15 and 16 and thereafter for the remainder of treatment. All participants with stable disease or better after 2 cycles could continue treatment until progressive disease or unacceptable toxicity.

Drug: Carfilzomib

Phase 1b Lymphoma: Carfilzomib 20/70 mg/m²

EXPERIMENTAL

Participants received carfilzomib 20 mg/m² administered by intravenous infusion over 30 minutes on Cycle 1 Days 1 and 2 only, then 70 mg/m² on Days 8, 9, 15 and 16 and thereafter for the remainder of treatment. All participants with stable disease or better after 2 cycles could continue treatment until progressive disease or unacceptable toxicity.

Drug: Carfilzomib

Phase 1b MM: Carfilzomib 20/45 mg/m² + Dexamethasone

EXPERIMENTAL

Participants received carfilzomib 20 mg/m² administered by intravenous infusion over 30 minutes on Cycle 1 Days 1 and 2 only, then 45 mg/m² on Days 8, 9, 15 and 16 and thereafter for the remainder of treatment plus dexamethasone 40 mg weekly. All participants with stable disease or better after 2 cycles could continue treatment until progressive disease or unacceptable toxicity.

Drug: Carfilzomib; Drug: Dexamethasone

Phase 1b MM: Carfilzomib 20/56 mg/m² + Dexamethasone

EXPERIMENTAL

Participants received carfilzomib 20 mg/m² administered by intravenous infusion over 30 minutes on Cycle 1 Days 1 and 2 only, then 56 mg/m² on Days 8, 9, 15 and 16 and thereafter for the remainder of treatment plus dexamethasone 40 mg weekly. All participants with stable disease or better after 2 cycles could continue treatment until progressive disease or unacceptable toxicity.

Drug: Carfilzomib; Drug: Dexamethasone

Interventions

Carfilzomib DRUG

Administered by intravenous (IV) bolus (2-10 minute) infusion or 30 minute infusion

Also known as: Kyprolis

Phase 1B Solid Tumors: Carfilzomib 20 mg/m² Bolus; Phase 1B Solid Tumors: Carfilzomib 20/27 mg/m² Bolus; Phase 1B Solid Tumors: Carfilzomib 20/36 mg/m² Bolus; Phase 1B Solid Tumors: Carfilzomib 20/45 mg/m²; Phase 1B Solid Tumors: Carfilzomib 20/56 mg/m²; Phase 1B Solid Tumors: Carfilzomib 20/70 mg/m²; Phase 1B Solid Tumors: Carfilzomib 36 mg/m²; Phase 1B Solid Tumors: Carfilzomib 45 mg/m²; Phase 1b Lymphoma: Carfilzomib 20/56 mg/m²; Phase 1b Lymphoma: Carfilzomib 20/70 mg/m²; Phase 1b MM: Carfilzomib 20/45 mg/m² + Dexamethasone; Phase 1b MM: Carfilzomib 20/56 mg/m² + Dexamethasone; Phase 1b Multiple Myeloma: Carfilzomib 20/36 mg/m²; Phase 1b Multiple Myeloma: Carfilzomib 20/45 mg/m²; Phase 1b Multiple Myeloma: Carfilzomib 20/56 mg/m²; Phase 1b Multiple Myeloma: Carfilzomib 20/70 mg/m²; Phase 2 Solid Tumors: Carfilzomib 20/36 mg/m² Bolus

Dexamethasone DRUG

Administered orally or by IV infusion prior to carfilzomib

Phase 1b MM: Carfilzomib 20/45 mg/m² + Dexamethasone; Phase 1b MM: Carfilzomib 20/56 mg/m² + Dexamethasone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Disease related
• Phase 1 Subjects (Bolus and Infusion):
• Solid Tumor:
• Histologically confirmed advanced solid tumor
• to 3 prior treatment regimens
• At least one site of radiographically measurable disease of ≥ 2 cm in the largest dimension by traditional computed tomography (CT) scanning technique or ≥ 1 cm in the largest dimension by spiral CT scanning (per Response Evaluation Criteria in Solid Tumors \[RECIST\] 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 (MM):
• 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 non-Hodgkin lymphoma (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.

You may not qualify if:

• 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 graft-versus-host disease (GVHD)
• 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 human immunodeficiency virus (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

Sponsors & Collaborators

• Amgen: lead

Study Sites (7)

Pinnacle Oncology

Scottsdale, Arizona, 85258, United States

Location

Tower Cancer Research Foundation

Beverly Hills, California, 90210, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Maryland Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

The Sarah Cannon Research Institute

Nashville, Tennessee, 37203-1632, United States

Location

South Texas Accelerated Research Therapeutics (START)

San Antonio, Texas, 78229, United States

Location

Related Publications (2)

• Papadopoulos KP, Siegel DS, Vesole DH, Lee P, Rosen ST, Zojwalla N, Holahan JR, Lee S, Wang Z, Badros A. Phase I study of 30-minute infusion of carfilzomib as single agent or in combination with low-dose dexamethasone in patients with relapsed and/or refractory multiple myeloma. J Clin Oncol. 2015 Mar 1;33(7):732-9. doi: 10.1200/JCO.2013.52.3522. Epub 2014 Sep 15.

  PMID: 25225420 DERIVED

• Ohshima-Hosoyama S, Davare MA, Hosoyama T, Nelon LD, Keller C. Bortezomib stabilizes NOXA and triggers ROS-associated apoptosis in medulloblastoma. J Neurooncol. 2011 Dec;105(3):475-83. doi: 10.1007/s11060-011-0619-0. Epub 2011 Jun 3.

  PMID: 21633906 DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms; Kidney Neoplasms; Carcinoma, Non-Small-Cell Lung; Small Cell Lung Carcinoma; Multiple Myeloma; Lymphoma

Interventions

carfilzomib; Dexamethasone

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Urologic Neoplasms; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Study Director
• Organization: Amgen, Inc.

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2007
• First Posted: September 18, 2007
• Study Start: September 1, 2007
• Primary Completion: October 1, 2014
• Study Completion: May 22, 2017
• Last Updated: August 15, 2017
• Results First Posted: December 9, 2015

Record last verified: 2017-07

Locations

US (7)