Nelfinavir as Bortezomib-sensitizing Drug in Patients With Proteasome Inhibitor-nonresponsive Myeloma

NCT02188537 | Completed Phase 2 DMC

• 2 other identifiers: SAKK 39/13 - FORTUNESNCTP000001061
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 12

Brief Summary

Trial objectives: To decide whether the addition of nelfinavir to the approved antimyeloma therapy with bortezomib and dexamethasone has sufficient activity in proteasome inhibitor-resistant myeloma patients to merit further clinical investigation in a prospective controlled trial. Additional research questions: To collect myeloma cell samples from proteasome inhibitor-resistant myeloma patients for the assessment of the biology of proteasome inhibitor resistance and the identification of predictive markers for response to nelfinavir-based antimyeloma therapy.

Conditions

Myeloma

Keywords

Myeloma; proteasome inhibitor-nonresponsive myeloma; Nelfinavir; bortezomib; bortezomib-sensitizing drug

Outcome Measures

Primary Outcomes (1)

• Response rate based on best response observed during the trial

  end of cycle 6 (at week 19)

Secondary Outcomes (6)

• Adverse events

  end of cycle 6 (at week 19)

• Proportion of patients achieving at least a minor response

  end of cycle 6 (at week 19)

• Disease control rate (no evidence of disease progression for at least 3 cycles)

  end of cycle 6 (at week 19)

• Time from registration to the start of the next new antimyeloma therapy or death from any cause

  end of cycle 6 (at week 19)

• Progressive disease under trial treatment

  end of cycle 6 (at week 19)

Study Arms (1)

Nelfinavir, Bortezomib, Dexamethasone

EXPERIMENTAL

The trial is designed as an "add-on" therapy, where nelfinavir is added to the approved bortezomib-containing therapy. Bortezomib and dexamethasone background treatment will be given in the Swissmedic-approved dose and schedule and according to international therapeutic standard.

Drug: Nelfinavir; Drug: bortezomib; Drug: Dexamethasone

Interventions

Nelfinavir DRUG

Nelfinavir 2x 2500 mg p.o. days 1 - 14

Also known as: Viracept

Nelfinavir, Bortezomib, Dexamethasone

bortezomib DRUG

Bortezomib 1.3 mg/m2 i.v. or s.c. days 1, 4, 8, 11

Also known as: Velcade®

Nelfinavir, Bortezomib, Dexamethasone

Dexamethasone DRUG

Dexamethasone 20 mg p.o. days 1-2, 4-5, 8-9, 11-12

Nelfinavir, Bortezomib, Dexamethasone

Eligibility Criteria

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

You may qualify if:

• Patient must give written informed consent prior to any protocol-specific procedure.
• Patient was diagnosed with multiple myeloma based on standard IMWG criteria, and has received at least one previous line of chemotherapy.
• Patient has been exposed to or is intolerant to at least one IMID (thalidomide, lenalidomide, pomalidomide).
• A therapy with bortezomib in the approved dose and schedule, based on Swissmedic approval (treatment of patients with relapsed/refractory multiple myeloma who have received at least one prior line of therapy), is indicated and intended.
• Patient is refractory to his/her most recent proteasome inhibitor-containing regimen, based on divers criteria.
• WHO performance status ≤ 3.
• Age ≥ 18 years.
• Adequate hematological values: platelets ≥ 50 x 109/L, hemoglobin ≥ 80 g/L (both may be achieved by transfusion).
• Adequate hepatic function: bilirubin ≤ 1.5 x ULN (for patients with suspected hemolysis: direct bilirubin ≤ 1.5 x ULN), ALT ≤ 3 x ULN (≤ 5 x ULN if liver infiltration by myeloma suspected, based on imaging results).
• Calculated creatinine clearance ≥ 15 mL/min, according to the formula of Cockcroft-Gault, see Appendix 1).
• Completed baseline QoL questionnaire.

You may not qualify if:

• Evidence of ongoing uncontrolled systemic infections.
• History of chronic active HCV or HBV.
• Evidence of myeloma within the CNS.
• Psychiatric disorder precluding understanding of information on trial related topics, giving informed consent, filling out quality of life (QoL) forms, or interfering with compliance for oral drug intake.
• Exposure to another experimental drug within 3 weeks prior to trial entry.
• Any serious underlying medical condition (at the judgment of the investigator) which may impair the ability of the patient to participate in the trial, in particular any uncontrolled clinically significant active disease (e.g. active autoimmune disease, uncontrolled diabetes, uncontrolled cardiac disease).
• Non-hematologic active malignancy within the past 5 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason Grade 6 or less with stable prostate-specific antigen levels; or d) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder or benign tumors of the adrenal or pancreas.
• Concomitant use of other anti-cancer medication or radiotherapy except for local pain control. The use of bisphosphonates is allowed.
• Significant neuropathy (Grades 3-4, or Grade 2 with pain) within 14 days prior to enrollment.
• Known hypersensitivity to bortezomib or nelfinavir or hypersensitivity to components of these drugs.
• Any psychological, familial, sociological or geographical condition likely hampering compliance with the trial protocol and follow-up.
• Patient who takes the following drugs during the trial therapy, which cannot be replaced or paused.

Sponsors & Collaborators

• Swiss Cancer Institute: lead

Study Sites (12)

Kantonsspital Aarau

Aarau, CH-5001, Switzerland

Location

Kantonsspital Baden

Baden, 5404, Switzerland

Location

Universitaetsspital-Basel

Basel, CH-4031, Switzerland

Location

Istituto Oncologico Svizzera Italiana IOSI

Bellinzona, 6500, Switzerland

Location

Inselspital Bern

Bern, 3010, Switzerland

Location

Kantonsspital Graubuenden

Chur, CH-7000, Switzerland

Location

Hopital Fribourgeois

Fribourg, 1708, Switzerland

Location

Hopital Cantonal Universitaire de Geneve

Geneva, CH-1211, Switzerland

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, CH-1011, Switzerland

Location

Kantonsspital - St. Gallen

Sankt Gallen, CH-9007, Switzerland

Location

SpitalSTS AG Simmental-Thun-Saanenland

Thun, 3600, Switzerland

Location

UniversitätsSpital Zürich

Zurich, 8091, Switzerland

Location

Related Publications (1)

• Driessen C, Muller R, Novak U, Cantoni N, Betticher D, Mach N, Rufer A, Mey U, Samaras P, Ribi K, Besse L, Besse A, Berset C, Rondeau S, Hawle H, Hitz F, Pabst T, Zander T. Promising activity of nelfinavir-bortezomib-dexamethasone in proteasome inhibitor-refractory multiple myeloma. Blood. 2018 Nov 8;132(19):2097-2100. doi: 10.1182/blood-2018-05-851170. Epub 2018 Sep 20. No abstract available.

  PMID: 30237154 RESULT

MeSH Terms

Conditions

Neoplasms, Plasma Cell

Interventions

Nelfinavir; Bortezomib; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Christoph Driessen, Prof MD

  Cantonal Hospital of St. Gallen

  STUDY CHAIR

• Panagiotis Samaras, MD

  Universitätsspital Zürich

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 3, 2014
• First Posted: July 11, 2014
• Study Start: December 2, 2014
• Primary Completion: July 26, 2016
• Study Completion: April 17, 2018
• Last Updated: June 26, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will not share

Locations

CH (12)