Metastatic MelanomaPhase 1NCT00734188
Dose Escalation and Safety Study of 188Re-PTI-6D2 in Patients With Metastatic Melanoma
A Phase 1 study testing PTI-6D2 in people with Metastatic Melanoma, run by Pain Therapeutics at 1 site in Israel.
Trial summary
This is an open-label, dose-escalation study to determine the safety, maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of 188Re-PTI-6D2 in patients with metastatic melanoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Melanoma
- What is being tested?
- PTI-6D2
- How many people
- 21 participants
- Where
- 1 siteIsrael
- Study dates
- Jan 2009to Jun 2010
- 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
- Patients must have histologically or clinically confirmed malignant melanoma of one of the following stages (according to 2002 American Joint Committee on Cancer criteria: Appendix C): Unresectable Stage III disease or Stage IV disease
- Patients must have measurable disease as defined by at least one target lesion ≥ 10 mm by spiral CT scan or ≥ 20 mm by conventional techniques
- Males or females ≥ 18 years of age
- Karnofsky performance status ≥ 60% (see Appendix D)
- Life expectancy of greater than three months
- Failure to respond to other therapy
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- At least 4 weeks since prior chemotherapy or radiation therapy and at least one week since IL-2 therapy
- Patients must not have significant organ and marrow dysfunction as defined by the following Screening laboratory values: Leukocytes ≥ 3,000/mcL; Absolute neutrophil count ≥ 1,500/mcL; Platelets ≥ 50,000/mcL; Total bilirubin ≤ 2.0 × upper limit of normal(ULN); AST(SGOT)/ALT(SGPT) ≤ 3 × ULN or ≤ 6 × ULN if liver metastases present; Creatinine ≤ 2.0 or creatinine clearance ≥ 60 mL/min/1.73 m2 if creatinine > 2.0
- Patients must have negative screening human anti-murine antibodies (HAMA).
- Females who are postmenopausal, physically incapable of childbearing, or practicing an acceptable method of birth control. Acceptable methods of birth control include surgical sterilization, hormonal contraceptives, or double-barrier methods (condom or diaphragm with a spermicidal agent or IUD). If practicing an acceptable method of birth control, a negative urine pregnancy test result has been obtained at the Screening Visit
- Patients must be able to understand study procedures and must sign a written informed consent form prior to entering the study
- Patients must agree to comply with all treatment procedures and be willing and able to remain at the study site unit for no less than 48 hours after infusion with 188Re-PTI-6D2 or later as determined by the Investigator's clinical judgment
Who cannot join
- Patients who have had chemotherapy or radiotherapy within 4 weeks (IL-2 therapy within one week) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- Patients who have participated in another investigational drug trial or therapeutic trial within 30 days of the Screening Visit
- Patients with brain metastases (must be confirmed by contrast-enhanced MRI within 4 weeks of study entry - a CT scan may be substituted for patients who cannot tolerate the MRI procedure)
- Patients with any ocular disease that, in the opinion of the PI, could lead to an impaired blood-retinal brain barrier: e.g. severe retinal detachment, ocular melanoma or other ocular neoplastic process, or ocular inflammatory disease
- Patients with a prior parenteral exposure to murine proteins or a history of allergy or hypersensitivity to investigational or approved antibodies
- HIV-positive patients on combination antiretroviral therapy are ineligible because of increased risk of lethal infections secondary to marrow-suppressive therapy
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- Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Patients who are pregnant or breast-feeding
- Patients who are unwilling to reside in the study unit for a minimum of 48 hours after infusion with 188Re-PTI-6D2 or later as determined by the Investigator's clinical judgment, or to cooperate fully with the investigator or site personnel
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Multi-Center, Open-Label, Phase I, Dose-Escalation and Safety Study of 188Re-PTI-6D2 in Patients With Metastatic Melanoma
This is an open-label, dose-escalation study to determine the safety, maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of 188Re-PTI-6D2 in patients with metastatic melanoma.
Read the detailed description
Patients with confirmed Stage III (unresectable) or Stage IV melanoma who meet all eligibility criteria will undergo thorough physical examination and baseline tumor imaging to document baseline tumor measurements. Patients will be allowed to check in to the study center either the evening prior to dosing (Study Day 0) or the day of dosing (Study Day 1) based upon the principal investigators (PIs) discretion. All patients will be dosed and monitored as inpatients during the study.
Patients will receive an intravenous (IV) infusion of 188Re-PTI-6D2. Patients will undergo serial gamma scans at specified time points. Blood samples will be obtained prior to dosing and at specified intervals for PK measurements of the mAb as well as for measurement of serum radioactivity. Urine will be collected to measure excreted radioactivity. Patients will be closely monitored for safety throughout the duration of the study. Patients will remain at the study center for 48-72 hours after infusion of the radiolabeled dose to allow adequate time for post-treatment safety observation and rhenium decay. No investigational or commercial agents or therapies other than the study agent may be administered with the intent to treat the patient's malignancy during the inpatient treatment period.
After three evaluable patients have been followed for a minimum of 2-6 weeks after 188Re-PTI-6D2 infusion, the Principal Investigator and the PTI Medical Monitor will review safety data for patients at the current dose level. If there is no evidence of a dose-limiting toxicity, the dose of 188Re-PTI-6D2 will be escalated for the next cohort of patients. Dose escalation of 188Re-PTI-6D2 will occur according to the following titration scheme:
Level 1 = 20-30 mCi 188Re-PTI-6D2 / 10 - 50 mg of antibody
Level 2 = 40-60 mCi 188Re-PTI-6D2 / 10 - 50 mg of antibody
Level 3 = 75-100 mCi 188Re-PTI-6D2 / 50 - 100 mg of antibody
Level 4 = 125-150 mCi 188Re-PTI-6D2 / 50 - 100 mg of antibody
Level 5 = 175-200 mCi 188Re-PTI-6D2 / 50 - 100 mg of antibody
Dose-limiting toxicity will be defined as the following: Grade 4 hematological toxicity; ≥ Grade 3 non-hematological toxicity; or any adverse event that results in permanent discontinuation of the infusion. If at any time Grade 5 toxicity is observed, accrual will be suspended until further review. If 0 out of 3 patients experience DLT, the next cohort of 3 patients will be enrolled at the next dose level. If 1 out of 3 patients experience a dose-limiting toxicity, an additional three evaluable patients will be enrolled at the current dose level.
Dose escalation occurs until the maximum tolerated dose is determined. The MTD is defined as the dose preceding the dose at which 2 of 3 or 2 of 6 patients experience DLT.
Safety will be evaluated by vital signs (blood pressure, heart rate, respiratory rate and temperature), physical examinations, electrocardiograms (EKGs), clinical laboratory tests and adverse event monitoring. Laboratory studies will include hematology, chemistry and urinalysis at baseline, at the end of the inpatient treatment period, and at 2 weeks and 6 weeks after the infusion of the 188Re-PTI-6D2 dose. If hematological recovery has not occurred by week 6, patients will follow-up monthly until hematological recovery. In addition, thyroid function tests will be performed at baseline and at 6 weeks after infusion; then monthly until recovery (if has not occurred). Human anti-murine antibodies (HAMA) will be measured at baseline, 2 weeks, and 6 weeks after infusion .
Biodistribution of 188Re-PTI-6D2 will be evaluated by whole body imaging with a gamma camera immediately after infusion (0 - 2 hrs.), at 2.5 - 5 hours, at 6 - 8 hours, and 24 hours post-infusion. Whole body imaging at 48 and 72 hours post-infusion may be conducted at the discretion of the PI. Urine will be collected to measure cumulative radioactivity excretion up to 48-72 hours post-infusion (depending on the hospital discharge date). Pharmacokinetics of the mAb and radioactivity will be determined from blood samples taken through 48-72 hours post-infusion (depending on the hospital discharge date). Dosimetry calculations will be performed to determine estimated absorbed radiation doses to critical organs and to tumor.
Patients will be discharged from the study unit 48-72 hours after infusion with 188Re-PTI-6D2 or later as determined by the Investigator's clinical judgment. Patients will be required to return for post-treatment follow-up visits approximately 2 and 6 weeks (± two days) after infusion for safety monitoring. Ongoing follow-up visits will continue until disease progression every 4 weeks. Tumor measurements will be performed at baseline, and all follow-up visits to assess for tumor response. Patients with unacceptable adverse events will have events followed until resolution.
- Conditions
- Metastatic Melanoma
- Being tested
- PTI-6D2
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PTI-6D2Drug
monoclonal antibody
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the maximum tolerated dose (MTD) of 188Re-PTI-6D2 in patients with metastatic melanoma
Measured: Daily/Weekly/Monthy
Secondary outcomes (1)
to determine safety and tolerability; dose-limiting toxicities; evaluate the anti-tumor activity; to evaluate the HAMA response; and, to further characterize the pharmacokinetics, biodistribution, and dosimetry of 188Re-PTI-6D2
Measured: Daily/Weekly/Monthly
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2008 (estimated)
- Study startJan 2009
- Primary completionMar 2010
- Study completionJun 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic MelanomaStudies 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
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Pain Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Eithan Galun, M.D., Principal investigator, Hadassah Hebrew University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00734188
- Sponsor's protocol ID
- PTI-6D2-B
- Status last verified
- Jul 2011
- First submitted
- 12 Aug 2008
- Last updated
- 14 Jul 2011
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Jul 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-Center, Open-Label, Phase I, Dose-Escalation and Safety Study of 188Re-PTI-6D2 in Patients With Metastatic Melanoma
- ClinicalTrials.gov ID
- NCT00734188
- Acronym / sponsor ID
- PTI-6D2-B
- Conditions
- Metastatic Melanoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (estimated)
- Lead sponsor
- Pain TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Jan 2009
- Primary completion
- Mar 2010 (actual)
- Study completion
- Jun 2010 (actual)
- First posted
- 14 Aug 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.
This is an open-label, dose-escalation study to determine the safety, maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of 188Re-PTI-6D2 in patients with metastatic melanoma.
Detailed description
Patients with confirmed Stage III (unresectable) or Stage IV melanoma who meet all eligibility criteria will undergo thorough physical examination and baseline tumor imaging to document baseline tumor measurements. Patients will be allowed to check in to the study center either the evening prior to dosing (Study Day 0) or the day of dosing (Study Day 1) based upon the principal investigators (PIs) discretion. All patients will be dosed and monitored as inpatients during the study.
Patients will receive an intravenous (IV) infusion of 188Re-PTI-6D2. Patients will undergo serial gamma scans at specified time points. Blood samples will be obtained prior to dosing and at specified intervals for PK measurements of the mAb as well as for measurement of serum radioactivity. Urine will be collected to measure excreted radioactivity. Patients will be closely monitored for safety throughout the duration of the study. Patients will remain at the study center for 48-72 hours after infusion of the radiolabeled dose to allow adequate time for post-treatment safety observation and rhenium decay. No investigational or commercial agents or therapies other than the study agent may be administered with the intent to treat the patient's malignancy during the inpatient treatment period.
After three evaluable patients have been followed for a minimum of 2-6 weeks after 188Re-PTI-6D2 infusion, the Principal Investigator and the PTI Medical Monitor will review safety data for patients at the current dose level. If there is no evidence of a dose-limiting toxicity, the dose of 188Re-PTI-6D2 will be escalated for the next cohort of patients. Dose escalation of 188Re-PTI-6D2 will occur according to the following titration scheme:
Level 1 = 20-30 mCi 188Re-PTI-6D2 / 10 - 50 mg of antibody
Level 2 = 40-60 mCi 188Re-PTI-6D2 / 10 - 50 mg of antibody
Level 3 = 75-100 mCi 188Re-PTI-6D2 / 50 - 100 mg of antibody
Level 4 = 125-150 mCi 188Re-PTI-6D2 / 50 - 100 mg of antibody
Level 5 = 175-200 mCi 188Re-PTI-6D2 / 50 - 100 mg of antibody
Dose-limiting toxicity will be defined as the following: Grade 4 hematological toxicity; ≥ Grade 3 non-hematological toxicity; or any adverse event that results in permanent discontinuation of the infusion. If at any time Grade 5 toxicity is observed, accrual will be suspended until further review. If 0 out of 3 patients experience DLT, the next cohort of 3 patients will be enrolled at the next dose level. If 1 out of 3 patients experience a dose-limiting toxicity, an additional three evaluable patients will be enrolled at the current dose level.
Dose escalation occurs until the maximum tolerated dose is determined. The MTD is defined as the dose preceding the dose at which 2 of 3 or 2 of 6 patients experience DLT.
Safety will be evaluated by vital signs (blood pressure, heart rate, respiratory rate and temperature), physical examinations, electrocardiograms (EKGs), clinical laboratory tests and adverse event monitoring. Laboratory studies will include hematology, chemistry and urinalysis at baseline, at the end of the inpatient treatment period, and at 2 weeks and 6 weeks after the infusion of the 188Re-PTI-6D2 dose. If hematological recovery has not occurred by week 6, patients will follow-up monthly until hematological recovery. In addition, thyroid function tests will be performed at baseline and at 6 weeks after infusion; then monthly until recovery (if has not occurred). Human anti-murine antibodies (HAMA) will be measured at baseline, 2 weeks, and 6 weeks after infusion .
Biodistribution of 188Re-PTI-6D2 will be evaluated by whole body imaging with a gamma camera immediately after infusion (0 - 2 hrs.), at 2.5 - 5 hours, at 6 - 8 hours, and 24 hours post-infusion. Whole body imaging at 48 and 72 hours post-infusion may be conducted at the discretion of the PI. Urine will be collected to measure cumulative radioactivity excretion up to 48-72 hours post-infusion (depending on the hospital discharge date). Pharmacokinetics of the mAb and radioactivity will be determined from blood samples taken through 48-72 hours post-infusion (depending on the hospital discharge date). Dosimetry calculations will be performed to determine estimated absorbed radiation doses to critical organs and to tumor.
Patients will be discharged from the study unit 48-72 hours after infusion with 188Re-PTI-6D2 or later as determined by the Investigator's clinical judgment. Patients will be required to return for post-treatment follow-up visits approximately 2 and 6 weeks (± two days) after infusion for safety monitoring. Ongoing follow-up visits will continue until disease progression every 4 weeks. Tumor measurements will be performed at baseline, and all follow-up visits to assess for tumor response. Patients with unacceptable adverse events will have events followed until resolution.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Patients must have histologically or clinically confirmed malignant melanoma of one of the following stages (according to 2002 American Joint Committee on Cancer criteria: Appendix C): Unresectable Stage III disease or Stage IV disease
- Patients must have measurable disease as defined by at least one target lesion ≥ 10 mm by spiral CT scan or ≥ 20 mm by conventional techniques
- Males or females ≥ 18 years of age
- Karnofsky performance status ≥ 60% (see Appendix D)
- Life expectancy of greater than three months
Key exclusion criteria (9 listed)
- Patients who have had chemotherapy or radiotherapy within 4 weeks (IL-2 therapy within one week) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- Patients who have participated in another investigational drug trial or therapeutic trial within 30 days of the Screening Visit
- Patients with brain metastases (must be confirmed by contrast-enhanced MRI within 4 weeks of study entry - a CT scan may be substituted for patients who cannot tolerate the MRI procedure)
- Patients with any ocular disease that, in the opinion of the PI, could lead to an impaired blood-retinal brain barrier: e.g. severe retinal detachment, ocular melanoma or other ocular neoplastic process, or ocular inflammatory disease
- Patients with a prior parenteral exposure to murine proteins or a history of allergy or hypersensitivity to investigational or approved antibodies
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 |
|---|---|---|
| PTI-6D2monoclonal antibody | Drug | – |
Primary outcome
To determine the maximum tolerated dose (MTD) of 188Re-PTI-6D2 in patients with metastatic melanoma
Time frame: Daily/Weekly/Monthy
1 secondary outcome
to determine safety and tolerability; dose-limiting toxicities; evaluate the anti-tumor activity; to evaluate the HAMA response; and, to further characterize the pharmacokinetics, biodistribution, and dosimetry of 188Re-PTI-6D2
Time frame: Daily/Weekly/Monthly
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 14 Jul 2011.
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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.
Eithan Galun, M.D. principal investigator
Hadassah Hebrew University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PTI-6D2 in people with Metastatic Melanoma, run by Pain Therapeutics at 1 site in Israel.
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 12 inclusion and 9 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 14 Jul 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. 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) of 188Re-PTI-6D2 in patients with metastatic melanoma (time frame: Daily/Weekly/Monthy). 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 14 Jul 2011.