NCT00531284

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

Completed Phase 1/Phase 2 Results posted Last updated 14 July 2017

What this trial tests

Phase 1/Phase 2 trial testing Carfilzomib in Ovarian Cancer in 184 participants. Completed in 22 May 2017.

Timeline

1 September 2007

Primary endpoint
1 October 2014

22 May 2017

Quick facts

Lead sponsor	Amgen
Phase	Phase 1/Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	184
Start date	1 September 2007
Primary completion	1 October 2014
Estimated completion	22 May 2017
Sites	7 locations across United States

Drugs / interventions tested

• Carfilzomib (carfilzomib) — full drug profile →
• Dexamethasone (dexamethasone) — full drug profile →

Conditions studied

• Ovarian Cancer — all drugs for Ovarian Cancer →
• Renal Cancer — all drugs for Renal Cancer →
• Non-small Cell Lung Cancer — all drugs for Non-small Cell Lung Cancer →
• Small Cell Lung Cancer — all drugs for Small Cell Lung Cancer →

Sponsor

Amgen — full company profile →

Who can join

18 and older, any sex, with Ovarian Cancer or Renal Cancer. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Phase 1b: Number of Participants With Dose-limiting Toxicities (DLT)
  Time frame: 28 days
  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
• Phase 2: Percentage of Participants With an Overall Response After 4 Treatment Cycles
  Time frame: 4 months
  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

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Proteasome inhibitors in cancer therapy.
   Manasanch EE, Orlowski RZ. · · 2017 · cited 743× · PMID 28117417 · DOI 10.1038/nrclinonc.2016.206
2. From epoxomicin to carfilzomib: chemistry, biology, and medical outcomes.
   Kim KB, Crews CM. · · 2013 · cited 126× · PMID 23575525 · DOI 10.1039/c3np20126k
3. CHAMPION-1: a phase 1/2 study of once-weekly carfilzomib and dexamethasone for relapsed or refractory multiple myeloma.
   Berenson JR, Cartmell A, Bessudo A, Lyons RM, et al · · 2016 · cited 82× · PMID 27207788 · DOI 10.1182/blood-2015-11-683854
4. The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.
   Tundo GR, Sbardella D, Santoro AM, Coletta A, et al · · 2020 · cited 78× · PMID 32442437 · DOI 10.1016/j.pharmthera.2020.107579
5. A phase I/II study of carfilzomib 2-10-min infusion in patients with advanced solid tumors.
   Papadopoulos KP, Burris HA, Gordon M, Lee P, et al · · 2013 · cited 64× · PMID 23975329 · DOI 10.1007/s00280-013-2267-x
6. Targeting Myc-driven stress addiction in colorectal cancer.
   Saeed H, Leibowitz BJ, Zhang L, Yu J. · · 2023 · cited 35× · PMID 37119690 · DOI 10.1016/j.drup.2023.100963
7. Clinical activity of carfilzomib correlates with inhibition of multiple proteasome subunits: application of a novel pharmacodynamic assay.
   Lee SJ, Levitsky K, Parlati F, Bennett MK, et al · · 2016 · cited 26× · PMID 27071340 · DOI 10.1111/bjh.14014
8. Blocking autophagy overcomes resistance to dual histone deacetylase and proteasome inhibition in gynecologic cancer.
   Bi J, Zhang Y, Malmrose PK, Losh HA, et al · · 2022 · cited 19× · PMID 35039480 · DOI 10.1038/s41419-022-04508-2