Solid TumorsPhase 1NCT00359294
A Phase I Study of Zalypsis (PM00104) in Subjects With Advanced Malignant Solid Tumors or Lymphoma
A Phase 1 study testing PM00104 in people with Solid Tumors and Lymphoma, run by PharmaMar at 2 sites in United States.
Trial summary
Phase I trial, dose escalating, prospective, open-label, non-randomized, multicenter study. The purpose is to determine the safety, tolerability, dose limiting toxicity (DLT) and recommended dose (RD) of PM00104, administered intravenously over 1 hour daily for 5 days every 3 weeks (this is considered as 1 cycle) to… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumors, Lymphoma
- What is being tested?
- PM00104
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 2 sitesUnited States
- Study dates
- May 2006to Sep 2008
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Voluntary written informed consent of the subject obtained before any study-specific procedure.
- Histologically or cytologically confirmed malignant solid tumor or lymphoma.
- Subjects with malignancies that are not otherwise curable or for which no effective standard therapy exists.
- Age ≥ 18 years.
- Subject with measurable or non-measurable disease using the RECIST criteria
- Recovery from any drug-related adverse event related to previous treatment, excluding alopecia and NCI-CTCAE grade < 2 peripheral neuropathy.
Show all 20Show fewer
- Laboratory values within 7 days prior to first infusion:
- Platelet count ≥ 100 x109/L, hemoglobin ≥ 9 g/dL and absolute neutrophil count (ANC) ≥ 1.5 x109/L.
- Alkaline phosphatase ≤ 2.5 x the upper limit of normal (ULN) (≤ 5 x ULN in case of extensive bone metastases)
- Aspartate aminotransferase (AST): ≤ 2.5 x ULN
- Alanine aminotransferase (ALT): ≤ 2.5 x ULN
- Total bilirubin: ≤ 1.5 ULN, unless due to Gilbert's syndrome.
- Creatinine: ≤ ULN, or calculated creatinine clearance: ≥ 60 mL/min (calculated from the Cockcroft-Gault formula; see Appendix III).
- Albumin: ≥ 2.5 g/dL.
- Partial thromboplastin within normal limits for the institution
- International normalized ratio (INR) within normal limits for the institution (unless due to oral anticoagulation)
- Performance status (ECOG) ≤ 1
- Life expectancy ≥ 3 months.
- Left ventricular ejection fraction (LVEF) within normal limits for the institution (LVEF of at least 50%).
- Women of childbearing potential must have a negative serum pregnancy test before study entry. Both men and women 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, oral contraceptive, subdermal implant and double barrier (condom with a contraceptive sponge or contraceptive suppository).
Who cannot join
- Prior therapy with PM00104
- Pregnant or lactating women.
- Less than 4 weeks from radiation therapy (8 weeks in case of extensive prior radiotherapy) or last dose of hormonal therapy, biological therapy or chemotherapy (6 weeks in case of nitrosourea, mitomycin C).
- Prior high dose chemotherapy that needed bone marrow transplant support.
- Subjects with untreated or uncontrolled brain or meningeal metastases.
- Other relevant diseases or adverse clinical conditions:
Show all 26Show fewer
- Increased cardiac risk as defined by:
- History or presence of unstable angina.
- History or presence of myocardial infarction.
- Congestive heart failure.
- Symptomatic arrhythmia or any arrhythmia requiring ongoing treatment.
- Abnormal ECG (i.e., patients with the following are excluded: QT prolongation-corrected QT interval > 480 msec-, signs of cardiac enlargement or hypertrophy, bundle branch block, partial bundle branch blocks, signs of ischemia or necrosis, Wolff-Parkinson-White patterns).
- History or presence of valvular heart disease.
- Uncontrolled arterial hypertension despite optimal medical therapy.
- Previous mediastinal radiotherapy.
- Previous treatment with doxorubicin at cumulative doses in excess of 400 mg/m2
- History of significant neurological or psychiatric disorders.
- Active infection.
- Significant non-neoplastic liver disease (e.g., cirrhosis, chronic active hepatitis).
- Significant non-neoplastic renal disease.
- Immunocompromised subjects, including subjects known to be infected by human immunodeficiency virus (HIV).
- Uncontrolled endocrine diseases (e.g., diabetes mellitus, hypothyroidism or hyperthyroidism, adrenal disorder) requiring relevant changes in medication within the last month or hospital admission within the last 3 months.
- Any other major illness that, in the investigator's judgment, could substantially increase the risk associated with the subject's participation in this study.
- Limitation of the subject's ability to comply with the treatment or to follow-up at a participating center. Subjects registered on this trial must be treated and followed at a participating center.
- Treatment with any investigational product in the 30 days period prior to the first infusion.
- Known hypersensitivity to any of the components of the drug product, including sucrose or potassium phosphate.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Massachusetts General Hospital
Boston, Massachusetts, 02115
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111-2497
About this study
Official title: A Phase I Multicenter, Open-label, Dose-escalating Clinical and Pharmacokinetic Study of PM00104 Administered Intravenously Over 1 Hour Daily for 5 Days, Every 3 Weeks, to Subjects With Advanced Malignant Solid Tumors or Lymphoma.
Phase I trial, dose escalating, prospective, open-label, non-randomized, multicenter study. The purpose is to determine the safety, tolerability, dose limiting toxicity (DLT) and recommended dose (RD) of PM00104, administered intravenously over 1 hour daily for 5 days every 3 weeks (this is considered as 1 cycle) to subjects with advanced malignant solid tumors or lymphoma.
Read the detailed description
Phase I trial, dose escalating, prospective, open-label, non-randomized, multicenter study. The purpose is to determine the safety, tolerability, dose limiting toxicity (DLT) and recommended dose (RD) of PM00104, administered intravenously over 1 hour daily for 5 days every 3 weeks (this is considered as 1 cycle) to subjects with advanced malignant solid tumors or lymphoma. Secondary objectives are to determine the preliminary pharmacokinetics of PM00104, to evaluate the relationship between pharmacokinetics/pharmacodynamics and to evaluate the preliminary antitumor activity of PM00104. Dose-escalation guidelines will follow an accelerated phase I design for conventional cytotoxic agents in order to minimize the number of subjects treated at the subtoxic dose levels. The trial will be conducted in compliance with the protocol, Good clinical practice (GCP) and applicable regulatory requirements.
- Conditions
- Solid Tumors, Lymphoma
- Being tested
- PM00104
- Keywords
- Tumor, Lymphoma, Zalypsis, PharmaMar, PM00104
- Medical subject headings
- Lymphoma, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PM00104Drug
Also called Zalypsis
Intravenously over 1 hour daily for 5 days, every 3 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Zalypsis (PM00104) | Experimental | Not described Receives: Drug: PM00104 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Patients With Dose Limiting Toxicities (DLT)
DLTs were defined as follows:
- Hematological adverse events:
- Any grade 4 neutropenia (absolute neutrophil count (ANC) < 0.5 x109/l) for longer than five days;
- Any grade 4 neutropenia accompanied by fever (at least 38.5°C);
- Any grade 4 neutropenia and sepsis or other severe infection;
- Any grade 4 thrombocytopenia.
- Any other grade 3/4 non-hematological adverse event (AE) and any increase of cardiac troponin I ≥0.1 ng/ml together with evidence of cardiac damage by electrocardiogram (ECG) or echocardiogram (ECHO), except for untreated nausea/vomiting or hypersensitivity reactions.
- Decrease in left ventricular ejection fraction (LVEF) > 20% compared to the patient's baseline value and/or LVEF < 50% below normal limits for the institution.
- Delay in the initiation of a subsequent dose exceeding two weeks due to drug related AEs
Measured: During the first cycle (21 days)
Secondary outcomes (1)
Overall Best Tumor Response
Best tumor response was defined as the best response achieved during the study according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.0. Complete response (CR): disappearance of all lesions; Partial response (PR): ≥10% decrease in target lesion size or ≥15% decrease in tumor density; Disease progression (PD): ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; Stable disease (SD): none of the CR, PR, or PD criteria met; RECIST,
Measured: every six weeks while on study, up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2006 (estimated)
- Study startMay 2006
- Primary completionSep 2008
- Study completionSep 2008
Why it stopped: Low recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- PharmaMar
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Roger Bryan Cohen, MD, Principal investigator, Fox Chase Cancer CenterEunice Lee Kwak, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00359294
- Sponsor's protocol ID
- PM104-A-002-05
- Status last verified
- Jul 2021
- First submitted
- 1 Aug 2006
- Last updated
- 28 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Multicenter, Open-label, Dose-escalating Clinical and Pharmacokinetic Study of PM00104 Administered Intravenously Over 1 Hour Daily for 5 Days, Every 3 Weeks, to Subjects With Advanced Malignant Solid Tumors or Lymphoma.
- ClinicalTrials.gov ID
- NCT00359294
- Acronym / sponsor ID
- PM104-A-002-05
- Conditions
- Solid Tumors, Lymphoma
- Keywords
- Tumor, Lymphoma, Zalypsis, PharmaMar, PM00104
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low recruitment
- Enrolment
- 12 participants (actual)
- Lead sponsor
- PharmaMarIndustry (pharma, biotech, devices)
- Study start
- May 2006
- Primary completion
- Sep 2008 (actual)
- Study completion
- Sep 2008 (actual)
- First posted
- 2 Aug 2006 (estimated)
- Results
- Posted 28 Jul 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Phase I trial, dose escalating, prospective, open-label, non-randomized, multicenter study. The purpose is to determine the safety, tolerability, dose limiting toxicity (DLT) and recommended dose (RD) of PM00104, administered intravenously over 1 hour daily for 5 days every 3 weeks (this is considered as 1 cycle) to subjects with advanced malignant solid tumors or lymphoma.
Detailed description
Phase I trial, dose escalating, prospective, open-label, non-randomized, multicenter study. The purpose is to determine the safety, tolerability, dose limiting toxicity (DLT) and recommended dose (RD) of PM00104, administered intravenously over 1 hour daily for 5 days every 3 weeks (this is considered as 1 cycle) to subjects with advanced malignant solid tumors or lymphoma. Secondary objectives are to determine the preliminary pharmacokinetics of PM00104, to evaluate the relationship between pharmacokinetics/pharmacodynamics and to evaluate the preliminary antitumor activity of PM00104. Dose-escalation guidelines will follow an accelerated phase I design for conventional cytotoxic agents in order to minimize the number of subjects treated at the subtoxic dose levels. The trial will be conducted in compliance with the protocol, Good clinical practice (GCP) and applicable regulatory requirements.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Zalypsis (PM00104) | Experimental | Drug: PM00104 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Voluntary written informed consent of the subject obtained before any study-specific procedure.
- Histologically or cytologically confirmed malignant solid tumor or lymphoma.
- Subjects with malignancies that are not otherwise curable or for which no effective standard therapy exists.
- Age ≥ 18 years.
- Subject with measurable or non-measurable disease using the RECIST criteria
Key exclusion criteria (26 listed)
- Prior therapy with PM00104
- Pregnant or lactating women.
- Less than 4 weeks from radiation therapy (8 weeks in case of extensive prior radiotherapy) or last dose of hormonal therapy, biological therapy or chemotherapy (6 weeks in case of nitrosourea, mitomycin C).
- Prior high dose chemotherapy that needed bone marrow transplant support.
- Subjects with untreated or uncontrolled brain or meningeal metastases.
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 |
|---|---|---|
| PM00104Also: ZalypsisIntravenously over 1 hour daily for 5 days, every 3 weeks. | Drug | Zalypsis (PM00104) |
Primary outcome
Patients With Dose Limiting Toxicities (DLT)
Time frame: During the first cycle (21 days)
DLTs were defined as follows: * Hematological adverse events: * Any grade 4 neutropenia (absolute neutrophil count (ANC) < 0.5 x109/l) for longer than five days; * Any grade 4 neutropenia accompanied by fever (at least 38.5°C); * Any grade 4 neutropenia and sepsis or other severe infection; * Any grade 4 thrombocytopenia. * Any other grade 3/4 non-hematological adverse event (AE) and any increase of cardiac troponin I ≥0.1 ng/ml together with evidence of cardiac damage by electrocardiogram (ECG) or echocardiogram (ECHO), except for untreated nausea/vomiting or hypersensitivity reactions. * Decrease in left ventricular ejection fraction (LVEF) > 20% compared to the patient's baseline value and/or LVEF < 50% below normal limits for the institution. * Delay in the initiation of a subsequent dose exceeding two weeks due to drug related AEs
1 secondary outcome
Overall Best Tumor Response
Time frame: every six weeks while on study, up to 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for 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
Active, not recruitingPhase 3
A Safety and Efficacy Extension Study of Pertuzumab in Patients With Solid Tumors Previously Enrolled in a Hoffmann-La Roche-Sponsored Pertuzumab Clinical Trial
Solid Tumors
RecruitingPhase 1
IL-12 Genetically Engineered Myeloid Cells in Participants With Relapsed, Refractory Solid Tumors
Relapsed Solid Tumor Malignancies, Refractory Solid Tumor Malignancies
RecruitingObservational study
Immune Checkpoint Inhibitor Toxicity Risk Prediction in Solid Tumors
Malignant Solid Neoplasm
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.
Roger Bryan Cohen, MD principal investigator
Fox Chase Cancer Center
Eunice Lee Kwak, MD principal investigator
Massachusetts General Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PM00104 in people with Solid Tumors and Lymphoma, run by PharmaMar at 2 sites in United States.
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 20 inclusion and 26 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: stopped early, as of the sponsor's last update on 28 Jul 2021. 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. 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?
Yes. Results are posted in the registry (first posted 28 Jul 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Patients With Dose Limiting Toxicities (DLT) (time frame: During the first cycle (21 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Jul 2021.