NCT00788099

Brief Summary

Phase I Multicenter, Open-label, Clinical and Pharmacokinetic Study of Plitidepsin in Combination with Sorafenib or Gemcitabine in Patients with Advanced Solid Tumors or Lymphomas to determine the maximum tolerated dose (MTD) and the recommended dose (RD) of plitidepsin in combination with sorafenib or gemcitabine in patients with advanced solid tumors or lymphomas.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
45

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Dec 2008

Typical duration for phase_1

Geographic Reach
2 countries

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 7, 2008

Completed
3 days until next milestone

First Posted

Study publicly available on registry

November 10, 2008

Completed
21 days until next milestone

Study Start

First participant enrolled

December 1, 2008

Completed
2.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2011

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2011

Completed
Last Updated

June 7, 2011

Status Verified

June 1, 2011

Enrollment Period

2.5 years

First QC Date

November 7, 2008

Last Update Submit

June 6, 2011

Conditions

Advanced Solid TumorsLymphomas

Keywords

AplidinPlitidepsinTumorsLymphomas

Outcome Measures

Primary Outcomes (1)

  • To determine the maximum tolerated dose (MTD) and the recommended dose (RD) of plitidepsin in combination with sorafenib or gemcitabine in patients with advanced solid tumors or lymphomas.

    Along the study

Secondary Outcomes (1)

  • To characterize safety profile and feasibility, pharmacokinetics, drug-drug interactions. To obtain information on antitumor activity.

    Along the study

Study Arms (2)

1

EXPERIMENTAL

Plitidepsin and Sorafenib

Drug: Plitidepsin and Sorafenib

2

EXPERIMENTAL

Gemcitabine and Plitidepsin

Drug: Gemcitabine and Plitidepsin

Interventions

Plitidepsin and SorafenibDRUG

Patients will receive i.v. plitidepsin over 1h on days 1, 8 and 15 every 4 weeks (d1, 8, 15 q4wk) and continuous oral sorafenib twice daily (bid) (a cycle is defined as an interval of 4 weeks).

1
Gemcitabine and PlitidepsinDRUG

Patients will receive i.v. gemcitabine over 30 minutes followed 1 hour later by plitidepsin over 1 hour on d1, 8, 15 q4wk (a cycle is defined as an interval of 4 weeks).

2

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age ≥ 18 years
  • ECOG performance status (PS) of ≤ 1
  • Life expectancy ≥ 3 months
  • Patients with histologically/cytologically confirmed diagnosis of advanced solid tumors or lymphomas (excluding B-cell derived lineage and/or primary cutaneous and/or leukemic disease) refractory to standard therapy and with reasonable chance to benefit from any of these combinations according to the investigator's opinion.
  • Patients entered at the expansion cohort of the RD must have: a) measurable disease according to RECIST, or to International Working Group Criteria (IWC) for lymphoma patients or b) Evaluable disease by serum markers in the case of prostate and ovarian cancer (according to Prostate-Specific Antigen Working Group Recommendations (PSAWGR) and Gynecologic Cancer Intergroup (GCIG) specific criteria, respectively
  • At least 4 weeks since last chemotherapy (6 weeks since nitrosoureas and mitomycin C), immunotherapy or any other pharmacological treatment and radiotherapy. In the case of hormone-sensitive cancer progressing while on hormone therapy (i.e., breast, prostate cancer), hormone therapy must be either stopped 4 weeks before or continued during the trial
  • Recovery to grade ≤1 from any AE derived from previous treatment (excluding alopecia of any grade and peripheral neuropathy ≤ grade 2)
  • LVEF by ECHO or MUGA above the lower normal limit.
  • Women of childbearing potential must have a negative serum pregnancy test before study entry. Both women and men must agree to use a medically acceptable method of contraception throughout the treatment period and for 3 months after discontinuation of treatment. Acceptable methods of contraception include complete abstinence, intrauterine device (IUD), oral contraceptive, subdermal implant and double barrier
  • Voluntarily signed and dated written informed consent prior to any specific study procedure.

You may not qualify if:

  • Previous treatment with any of the study drugs (in the expansion cohort at the RD).
  • Concomitant diseases/conditions:
  • History or presence of unstable angina, myocardial infarction, valvular heart disease or congestive heart failure.
  • Previous mediastinal radiotherapy.
  • Previous treatment with doxorubicin at cumulative doses in excess of 450 mg/m2
  • Symptomatic arrhythmia or any arrhythmia requiring ongoing treatment, and/or prolonged QT-QTc \> to grade 1.
  • Active uncontrolled infection.
  • Myopathy or any clinical situation that causes significant and persistent elevation of CPK (\>2.5 x ULN in two different determinations performed with one week apart).
  • Limitation of the patient's ability to comply with the treatment or follow-up protocol.
  • Any other major illness that, in the Investigator's judgment, will substantially increase the risk associated with the patient's participation in this study.
  • Peripheral neuropathy \>grade 2
  • Symptomatic, progressive or requiring-corticosteroids documented brain metastases or leptomeningeal disease. Controlled and stable brain metastases without steroids are allowed
  • Men or women of childbearing potential who are not using an effective method of contraception as previously described; women who are pregnant or breast feeding
  • Patients who have had radiation therapy in greater than 35% of the bone marrow
  • History of previous bone marrow and/or stem cell transplantation. (Not for patients treated at RD in the expansion cohort)
  • +7 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

The Cancer Institute of New Jersey (CINJ)

New Brunswick, New Jersey, 08901, United States

Location

Institut Gustave Roussy

Villejuif, 94800, France

Location

MeSH Terms

Conditions

LymphomaNeoplasms

Interventions

plitidepsinSorafenibGemcitabine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic TypeLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Intervention Hierarchy (Ancestors)

Phenylurea CompoundsUreaAmidesOrganic ChemicalsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsNiacinamideNicotinic AcidsAcids, HeterocyclicHeterocyclic CompoundsPyridinesHeterocyclic Compounds, 1-RingDeoxycytidineCytidinePyrimidine NucleosidesPyrimidines

Study Officials

  • Mark N. Stein, MD

    Rutgers Cancer Institute of New Jersey

    PRINCIPAL INVESTIGATOR

  • Jean Charles Soria, MD

    Gustave Roussy, Cancer Campus, Grand Paris

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY

Study Record Dates

First Submitted

November 7, 2008

First Posted

November 10, 2008

Study Start

December 1, 2008

Primary Completion

June 1, 2011

Study Completion

June 1, 2011

Last Updated

June 7, 2011

Record last verified: 2011-06

Locations

US(1)FR(1)