EsophagealPhase 1/2MnSODNCT00618917
MnSOD (Esophageal Protectant) to Prevent Esophagitis During Radiation/Chemotherapy Treatment for Non-Small Cell Lung Cancer (NSCLC)
A Phase 1/2 study testing Manganese Superoxide Dismutase Plasmid Liposome, carboplatin and paclitaxel in people with Esophageal and Toxicity, run by Joel Greenberger at 1 site in United States.
Trial summary
This is a Phase I-II study evaluating the feasibility, safety, and efficacy of swallowed MnSOD plasmid/liposome (PL) transgene given as protection against radiation-induced esophagitis during concurrent paclitaxel and carboplatin chemotherapy with thoracic radiation in subjects with locally advanced non-small cell… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Esophageal, Toxicity
- What is being tested?
- Manganese Superoxide Dismutase Plasmid Liposome, carboplatin and paclitaxel
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Nov 2005to 11 Aug 2011
- Phase
- Phase 1/2
- 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
- Histologically or cytologically documented NSCLC including squamous cell carcinoma, adenocarcinoma (including bronchoalveolar cell), and large cell anaplastic carcinoma (including giant and clear cell carcinomas) and poorly differentiated non-small cell lung cancer. Totally resected tumors are excluded.
- Subjects must be without evidence of M0.
- Subjects with T1 or T2 disease with N2 or tumor stage 3, lymph node metastasis 1-2 ( stage 1) disease (Stage IIIA) are eligible if they are medically inoperable. Subjects with T4 with any N or any T with N3 disease are eligible. Radiographic evidence of mediastinal lymph nodes >2.0 cm in the largest diameter is sufficient to stage N2 or N3 disease. If the largest mediastinal node is < 2.0 cm in diameter and this is the basis for stage III disease, then at least one of the nodes must be proven positive cytologically or histologically.
- Subjects with tumors adjacent to a vertebral body are eligible as long as all gross disease can be encompassed in the radiation boost field. The boost volume must be limited to < 50% of the ipsilateral lung volume.
- Subjects with a pleural effusion that is a transudate, cytologically negative and non-bloody are eligible if the radiation oncologists feel the tumor can still be encompassed within a reasonable field of radiotherapy. Exudative, bloody, or cytologically malignant effusions are ineligible. If a pleural effusion can be seen on the chest CT but not on chest X-ray and is too small to tap, the subject will be eligible.
- Subjects must be deemed a suitable candidate for protocol treatment by both Radiation Oncology and Medical Oncology
Show all 16Show fewer
- Subjects must have a Performance Status > 70 (Karnofsky Performance Scale).
- Subjects Weight loss < 10% in 3 months prior to diagnosis.
- Subjects must be male or female > 18 years.
- Subjects must have had no prior systemic chemotherapy, radiation therapy to the thorax, or total surgical resection.
- At least 3 weeks since formal exploratory thoracotomy and the subject has recovered from surgery, or 1 week from diagnostic thoracoscopy.
- Laboratory values must be as follows: (See Section 6.1 of the full protocol for required timing): Granulocytes > 2,000/ml, Platelets > 100,000/ml, Hemoglobin* > 8 mg/dl, Bilirubin < 1.5 x normal, Creatinine clearance > 50 ml/n (24 hour or calculated, forced expiratory volume at one second > 800 cc. Note: *Physician can maintain a subject's hemoglobin with the use of Erythropoetin or transfusions prophylactic use of G-CSF (colony stimulating factor, is not permitted).
- Subjects must have a MRI or CT brain scan within 4 weeks prior to study entry to rule out asymptomatic brain metastases.
- Subjects must be informed of the investigational nature of the study and sign an informed consent form and have no serious medical or psychiatric illnesses that would prevent informed consent.
- No history of serious cardiac disease that is not adequately controlled.
- Female subjects must be non-pregnant and non-lactating. Female subjects of childbearing potential must implement an effective method of contraception during the study. All women of childbearing potential must have a pre-study negative serum or urine pregnancy test within 7 days prior to study entry.
Who cannot join
- Inability to meet any of the above eligibility requirements
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pittsburgh
Pittsburgh, Pennsylvania, 15232
About this study
Official title: Chemotherapy (Paclitaxel and Carboplatin)and Thoracic Radiotherapy With Swallowed Manganese Superoxide Dismutase (MnSOD) Plasmid Liposome Protection in Patients With Locally Advanced Stage III Non-Small Cell Lung Cancer: A Phase I-II Study
This is a Phase I-II study evaluating the feasibility, safety, and efficacy of swallowed MnSOD plasmid/liposome (PL) transgene given as protection against radiation-induced esophagitis during concurrent paclitaxel and carboplatin chemotherapy with thoracic radiation in subjects with locally advanced non-small cell lung cancer (NSCLC).
Read the detailed description
This is a Phase I-II study evaluating the feasibility, safety, and efficacy of swallowed MnSOD plasmid/liposome (PL) transgene given as protection against radiation-induced esophagitis during concurrent paclitaxel and carboplatin chemotherapy with thoracic radiation in subjects with locally advanced non-small cell lung cancer (NSCLC). Phase I of the study will assess the feasibility and safety of MnSOD PL by dose escalation in 3 cohorts of 3 chemoradiotherapy subjects each (Cohort1 = 0.3 mg/dose, Cohort2 = 3 mg/dose, Cohort3 = 30 mg/dose). The highest dose completed (as determined by toxicity monitoring for 8 weeks from initial treatment) will be the starting dose for Phase II. Phase II will examine the efficacy of MnSOD PL by assessing the incidence of Grade 3 or 4 esophagitis in 27 additional chemoradiotherapy subjects. Incidence of esophageal toxicity, as well as clinical response to the combination of chemoradiotherapy with MnSOD PL are the outcomes of interest.
- Conditions
- Esophageal, Toxicity
- Being tested
- Manganese Superoxide Dismutase Plasmid Liposome, carboplatin, paclitaxel, Radiation Therapy
- Keywords
- NSCLC, lung cancer, chemotherapy, radiation therapy, radiation toxicity
- Medical subject headings
- Lung Neoplasms, Radiation Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Manganese Superoxide Dismutase Plasmid LiposomeGenetic
Also called MnSOD/PL
15 ml of liquid that contains either 0.3 mg, 3.0 mg or 30.0 mg (depending on which cohort is open when the subject is entered) of MnSOD PL This will be given on Day 1 and 3 of each week of the experimental treatment for a total of 14 doses.
carboplatinDrug
Also called Paraplatin
Chemotherapy to stop the growth of tumor cells.
paclitaxelDrug
Also called Taxol
Chemotherapy to stop the growth of tumor cells. This drug kills tumor cells by inducing multipolar divisions. Cells entering mitosis in the presence of concentrations of paclitaxel equivalent to those in human breast tumors form abnormal spindles that contain additional spindle poles.
Radiation TherapyRadiation
1.9-2.1 Gy daily 5 times per week (4-6 hr after the first MnSOD PL dose). The total dose planned at 77.0 Gy with a range of 69-84Gy in 34-38 fractions over 7-8 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Radiation + MnSOD PL + Paclitaxel + Carboplatin | Experimental | MnSOD PL (0.3, 3, or 30 mg) + (Paclitaxel + Carboplatin (45mg/m^2)) + Radiation 1.9-2.1 Gy daily 5 times per week (4-6 hr after the first MnSOD PL dose). The total dose planned at 77.0 Gy with a range of 69-84Gy in 34-38 fractions over 7-8 weeks. Receives: Genetic: Manganese Superoxide Dismutase Plasmid Liposome; Drug: carboplatin; Drug: paclitaxel; Radiation: Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determination of Recommended Phase II Dose of MnSOD/Plasmid DNA
The maximally tolerated dose (milligrams) defined as the highest dose with fewer than one-third of patients experiencing a dose-limiting toxicity (DLT) per CTCAE v3.0 due to MnSOD.
(Three patients treated at each at three tiers of 0.3, 3, and 30mg of MnSOD/plasmid DNA. If no DLTs (grade III/IV toxicity due to MnSOD PL) observed, the dose of MnSOD PL escalated to the next tier. If one DLT observed, the cohort is expanded to six patients. If two of six patients experienced a DLT, dose escalation stops and the next lowest dose declared maximum tolerated dose (MTD). If none of three or one of six patients experience DLT at the 30-mg tier, that dose is defined as the starting dose for the efficacy phase and the MTD would be undefined).
Measured: Every 8 weeks, up to 2 years
Radiation-induced Esophageal Toxicity
Number of patients experiencing grade III/IV esophageal toxicity per CTCAE v3.0.
Measured: Up to 2 years
Secondary outcomes (3)
Overall (Objective) Response
Clinical Response per Response Evaluation Criteria in Solid Tumors (RECIST). Per RECIST v1.0: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (target or non-target) with reduction in short axis to <10 mm. Partial Response (PR): ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease: Neither sufficient shrinkage (compared to baseline) to qualify for partial or complete response (CR or PR) nor sufficient increase (taking as reference the smallest sum of diameters at baseline or while on study, whichever is smallest) to qualify for progressive disease (PD). Progressive Disease (PD): At least a 20%increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Measured: Up to 2 years
Overall Survival (OS)
The length of time from start of treatment that diagnosed patients remain alive.
Measured: Up to 5 years
Time to Disease Progression
The length of time from start of treatment until patients first disease recurrence/progression. Per RECIST v1.0: Progressive Disease (PD): At least a 20%increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2008 (estimated)
- Study start11 Nov 2005
- Primary completion26 Feb 2010
- Study completion11 Aug 2011
Why it stopped: MnSOD longer available during Phase II
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 EsophagealStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Joel Greenberger
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Joel Greenberger, University of Pittsburgh
- Investigators
- Joel Greenberger, MD, Principal investigator, UPMC Hillman Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00618917
- Sponsor's protocol ID
- 01-054
- Other IDs
- UPCI 01-054
- Acronym
- MnSOD
- Status last verified
- Oct 2021
- First submitted
- 6 Feb 2008
- Last updated
- 12 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Chemotherapy (Paclitaxel and Carboplatin)and Thoracic Radiotherapy With Swallowed Manganese Superoxide Dismutase (MnSOD) Plasmid Liposome Protection in Patients With Locally Advanced Stage III Non-Small Cell Lung Cancer: A Phase I-II Study
- ClinicalTrials.gov ID
- NCT00618917
- Acronym / sponsor ID
- MnSOD / 01-054
- Conditions
- Esophageal, Toxicity
- Keywords
- NSCLC, lung cancer, chemotherapy, radiation therapy, radiation toxicity
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: MnSOD longer available during Phase II
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Joel GreenbergerUniversity, hospital or other
- Study start
- 11 Nov 2005 (actual)
- Primary completion
- 26 Feb 2010 (actual)
- Study completion
- 11 Aug 2011 (actual)
- First posted
- 20 Feb 2008 (estimated)
- Results
- Posted 12 Nov 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase I-II study evaluating the feasibility, safety, and efficacy of swallowed MnSOD plasmid/liposome (PL) transgene given as protection against radiation-induced esophagitis during concurrent paclitaxel and carboplatin chemotherapy with thoracic radiation in subjects with locally advanced non-small cell lung cancer (NSCLC).
Detailed description
This is a Phase I-II study evaluating the feasibility, safety, and efficacy of swallowed MnSOD plasmid/liposome (PL) transgene given as protection against radiation-induced esophagitis during concurrent paclitaxel and carboplatin chemotherapy with thoracic radiation in subjects with locally advanced non-small cell lung cancer (NSCLC). Phase I of the study will assess the feasibility and safety of MnSOD PL by dose escalation in 3 cohorts of 3 chemoradiotherapy subjects each (Cohort1 = 0.3 mg/dose, Cohort2 = 3 mg/dose, Cohort3 = 30 mg/dose). The highest dose completed (as determined by toxicity monitoring for 8 weeks from initial treatment) will be the starting dose for Phase II. Phase II will examine the efficacy of MnSOD PL by assessing the incidence of Grade 3 or 4 esophagitis in 27 additional chemoradiotherapy subjects. Incidence of esophageal toxicity, as well as clinical response to the combination of chemoradiotherapy with MnSOD PL are the outcomes of interest.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Radiation + MnSOD PL + Paclitaxel + Carboplatin | Experimental | Genetic: Manganese Superoxide Dismutase Plasmid Liposome, Drug: carboplatin, Drug: paclitaxel, Radiation: Radiation TherapyMnSOD PL (0.3, 3, or 30 mg) + (Paclitaxel + Carboplatin (45mg/m^2)) + Radiation 1.9-2.1 Gy daily 5 times per week (4-6 hr after the first MnSOD PL dose). The total dose planned at 77.0 Gy with a range of 69-84Gy in 34-38 fractions over 7-8 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Histologically or cytologically documented NSCLC including squamous cell carcinoma, adenocarcinoma (including bronchoalveolar cell), and large cell anaplastic carcinoma (including giant and clear cell carcinomas) and poorly differentiated non-small cell lung cancer. Totally resected tumors are excluded.
- Subjects must be without evidence of M0.
- Subjects with T1 or T2 disease with N2 or tumor stage 3, lymph node metastasis 1-2 ( stage 1) disease (Stage IIIA) are eligible if they are medically inoperable. Subjects with T4 with any N or any T with N3 disease are eligible. Radiographic evidence of mediastinal lymph nodes >2.0 cm in the largest diameter is sufficient to stage N2 or N3 disease. If the largest mediastinal node is < 2.0 cm in diameter and this is the basis for stage III disease, then at least one of the nodes must be proven positive cytologically or histologically.
- Subjects with tumors adjacent to a vertebral body are eligible as long as all gross disease can be encompassed in the radiation boost field. The boost volume must be limited to < 50% of the ipsilateral lung volume.
- Subjects with a pleural effusion that is a transudate, cytologically negative and non-bloody are eligible if the radiation oncologists feel the tumor can still be encompassed within a reasonable field of radiotherapy. Exudative, bloody, or cytologically malignant effusions are ineligible. If a pleural effusion can be seen on the chest CT but not on chest X-ray and is too small to tap, the subject will be eligible.
Key exclusion criteria (1 listed)
- Inability to meet any of the above eligibility requirements
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 |
|---|---|---|
| Manganese Superoxide Dismutase Plasmid LiposomeAlso: MnSOD/PL15 ml of liquid that contains either 0.3 mg, 3.0 mg or 30.0 mg (depending on which cohort is open when the subject is entered) of MnSOD PL This will be given on Day 1 and 3 of each week of the experimental treatment for a total of 14 doses. | Genetic | Radiation + MnSOD PL + Paclitaxel + Carboplatin |
| carboplatinAlso: ParaplatinChemotherapy to stop the growth of tumor cells. | Drug | Radiation + MnSOD PL + Paclitaxel + Carboplatin |
| paclitaxelAlso: TaxolChemotherapy to stop the growth of tumor cells. This drug kills tumor cells by inducing multipolar divisions. Cells entering mitosis in the presence of concentrations of paclitaxel equivalent to those in human breast tumors form abnormal spindles that contain additional spindle poles. | Drug | Radiation + MnSOD PL + Paclitaxel + Carboplatin |
| Radiation Therapy1.9-2.1 Gy daily 5 times per week (4-6 hr after the first MnSOD PL dose). The total dose planned at 77.0 Gy with a range of 69-84Gy in 34-38 fractions over 7-8 weeks. | Radiation | Radiation + MnSOD PL + Paclitaxel + Carboplatin |
Primary outcome
Determination of Recommended Phase II Dose of MnSOD/Plasmid DNA
Time frame: Every 8 weeks, up to 2 years
The maximally tolerated dose (milligrams) defined as the highest dose with fewer than one-third of patients experiencing a dose-limiting toxicity (DLT) per CTCAE v3.0 due to MnSOD. (Three patients treated at each at three tiers of 0.3, 3, and 30mg of MnSOD/plasmid DNA. If no DLTs (grade III/IV toxicity due to MnSOD PL) observed, the dose of MnSOD PL escalated to the next tier. If one DLT observed, the cohort is expanded to six patients. If two of six patients experienced a DLT, dose escalation stops and the next lowest dose declared maximum tolerated dose (MTD). If none of three or one of six patients experience DLT at the 30-mg tier, that dose is defined as the starting dose for the efficacy phase and the MTD would be undefined).
Radiation-induced Esophageal Toxicity
Time frame: Up to 2 years
Number of patients experiencing grade III/IV esophageal toxicity per CTCAE v3.0.
3 secondary outcomes
Overall (Objective) Response
Time frame: Up to 2 years
Overall Survival (OS)
Time frame: Up to 5 years
Time to Disease Progression
Time frame: Up to 5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Nov 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Joel Greenberger, MD principal investigator
UPMC Hillman Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Manganese Superoxide Dismutase Plasmid Liposome, carboplatin and paclitaxel in people with Esophageal and Toxicity, run by Joel Greenberger at 1 site 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 16 inclusion and 1 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 12 Nov 2021. 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 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 12 Nov 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?
Determination of Recommended Phase II Dose of MnSOD/Plasmid DNA (time frame: Every 8 weeks, up to 2 years). The study lists 2 primary outcomes in all. 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 12 Nov 2021.