Advanced Solid TumorsPhase 1NCT00788099

Study of Plitidepsin in Combination With Sorafenib or Gemcitabine in Patients With Advanced Solid Tumors or Lymphomas

A Phase 1 study testing Plitidepsin and Sorafenib and Gemcitabine and Plitidepsin in people with Advanced Solid Tumors and Lymphomas, run by PharmaMar at 2 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Advanced Solid Tumors, Lymphomas
What is being tested?: Plitidepsin and Sorafenib and Gemcitabine and Plitidepsin
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 45 participants
Where: 2 sitesin 2 countries
Study dates: Dec 2008to Jun 2011
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

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Adequate bone marrow, renal, hepatic, and metabolic function (assessed ≤ 7 days before inclusion in the study): a) Platelet count ≥100 x109/L (≥ 75 x 109/L for lymphoma patients), hemoglobin ≥9.0 g/dL (≥ 8.0 g/dL for lymphoma patients) and absolute neutrophil count (ANC) ≥1.5 x109/L (≥1.0 x109/L for lymphoma patients). b) Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT): ≤ 3.0 x the upper limit of normal (ULN), independently of the presence of liver metastases. c) AP ≤2.5 x ULN (≤5 x ULN in case of extensive bone metastases). d) Total bilirubin ≤1.5 x ULN (unless due to indirect hyperbilirubinemia for the gemcitabine combination arm only). e) Calculated CrCl: ≥ 40 mL/minute (by means of Crockroft and Gault´s formula). f) CPK ≤ 2.5 x ULN. g) Albumin ≥2.5 g/dL. h) Troponin I ≤ULN
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.

Who cannot join

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.

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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)
High transfusional requirements (> 2 packages of red blood cells and/or 1 platelets transfusion) in the 30 days prior to inclusion in the study
Participation in another clinical trial or concomitant treatment with any investigational product in the 30-day period prior to inclusion in the study.
For sorafenib treatment only: a) Hypersensitivity to sorafenib or any component of the formulation. b) Need of chronic exposure to antacids, H-2 antagonists or proton-pump inhibitors. c) Current need for anticoagulation treatment (including low dose warfarin and LMWH treatment at full anticoagulant doses).
Abnormal thyroid function [as per normal serum thyroid stimulating hormone (TSH) within 14 days of first dose of study treatment).
Uncontrolled arterial hypertension (≥160/100) despite optimal medical therapy.
Child-Pugh grade C hepatic cirrhosis of any cause
For gemcitabine treatment only:
Hypersensitivity to gemcitabine or any component of the formulation.
Impending need for palliative radiotherapy to ameliorate painful metastases.

Trial locations and contacts

2 sites in 2 countries.

Country

City, postcode or hospital

2 sites in 2 countries

United States1 site

The Cancer Institute of New Jersey (CINJ)
New Brunswick, New Jersey, 08901

Other trials in United States

France1 site

Institut Gustave Roussy
Villejuif, 94800

Other trials in France

About this study

Official title: 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

Read the detailed description

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), the pharmacokinetics (PK) of these combinations, drug-drug PK interactions, preliminary information on the clinical antitumor activity of these combinations in solid tumors,perform a preliminary pharmacogenomic (PGx) study of potential biomarkers of sensitivity/resistance to these drugs combinations and of prognostic markers of the treatment outcome in tumor tissue sample.

Conditions: Advanced Solid Tumors, Lymphomas
Being tested: Plitidepsin and Sorafenib, Gemcitabine and Plitidepsin
Keywords: Aplidin, Plitidepsin, Tumors, Lymphomas
Medical subject headings: Lymphoma, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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).
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).

Study groups in NCT00788099
Study group	Role	What they receive
1	Experimental	Plitidepsin and Sorafenib Receives: Drug: Plitidepsin and Sorafenib
2	Experimental	Gemcitabine and Plitidepsin Receives: Drug: Gemcitabine and Plitidepsin

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Along the study

Secondary outcomes (1)

To characterize safety profile and feasibility, pharmacokinetics, drug-drug interactions. To obtain information on antitumor activity.
Measured: Along the study

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Dec 2008Jun 2011

First posted10 Nov 2008 (estimated)
Study startDec 2008
Primary completionJun 2011
Study completionJun 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Advanced Solid TumorsStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 45 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00788099
Sponsor's protocol ID: APL-A-010-08
Status last verified: Jun 2011
First submitted: 7 Nov 2008
Last updated: 7 Jun 2011
Results posted: No
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Neoplasms
RecruitingPhase 1/2
A Study of Neladalkib (NVL-655) in Patients With Advanced NSCLC and Other Solid Tumors Harboring ALK Rearrangement or Activating ALK Mutation (ALKOVE-1)
Locally Advanced Solid Tumor, Metastatic Solid Tumor
Active, not recruitingPhase 2
Testing AZD5363 as a Potential Targeted Treatment in Cancers With AKT Genetic Changes (MATCH-Subprotocol Y)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm
RecruitingPhase 1/2
Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma

All Advanced Solid Tumors trials

Study at a glance

From the registry record, last updated by the sponsor on 7 Jun 2011. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT00788099
Acronym / sponsor ID: APL-A-010-08
Conditions: Advanced Solid Tumors, Lymphomas
Keywords: Aplidin, Plitidepsin, Tumors, Lymphomas
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 45 participants (actual)
Lead sponsor: PharmaMarIndustry (pharma, biotech, devices)
Study start: Dec 2008
Primary completion: Jun 2011 (actual)
Study completion: Jun 2011 (actual)
First posted: 10 Nov 2008 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
1	Experimental	Drug: Plitidepsin and SorafenibPlitidepsin and Sorafenib
2	Experimental	Drug: Gemcitabine and PlitidepsinGemcitabine and Plitidepsin

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (11 listed)

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

Key exclusion criteria (24 listed)

Previous treatment with any of the study drugs (in the expansion cohort at the RD).
Concomitant diseases/conditions:
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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Plitidepsin and SorafenibPatients 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).	Drug	1
Gemcitabine and PlitidepsinPatients 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).	Drug	2

Primary outcome

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.
Time frame: Along the study

1 secondary outcome

To characterize safety profile and feasibility, pharmacokinetics, drug-drug interactions. To obtain information on antitumor activity.
Time frame: Along the study

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Jun 2011.

Related trials for Advanced Solid Tumors

RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Neoplasms
RecruitingPhase 1/2
A Study of Neladalkib (NVL-655) in Patients With Advanced NSCLC and Other Solid Tumors Harboring ALK Rearrangement or Activating ALK Mutation (ALKOVE-1)
Locally Advanced Solid Tumor, Metastatic Solid Tumor
Active, not recruitingPhase 2
Testing AZD5363 as a Potential Targeted Treatment in Cancers With AKT Genetic Changes (MATCH-Subprotocol Y)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm
RecruitingPhase 1/2
Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Mark N. Stein, MD principal investigator

Rutgers Cancer Institute of New Jersey

Jean Charles Soria, MD principal investigator

Gustave Roussy, Cancer Campus, Grand Paris

2 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Plitidepsin and Sorafenib and Gemcitabine and Plitidepsin in people with Advanced Solid Tumors and Lymphomas, run by PharmaMar at 2 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Jun 2011. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States, France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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. (time frame: Along the study). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00788099.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jun 2011; AzTrials last refreshed its copy on 7 Nov 2026.