Combination Gene Transfer and Chemotherapy

March 13, 2020 updated by: Abramson Cancer Center of the University of Pennsylvania

A Pilot And Feasibility Trial Evaluating Two Different Chemotherapy Regimens In Combination With Intrapleural Adenoviral-Mediated Interferon-Alpha Gene Transfer For Malignant Pleural Mesothelioma

The purpose of this study is to find the safety of combination gene therapy and chemotherapy in patients with malignant pleural mesothelioma. Pleural catheter will be placed first, then pts will receive 2 doses of intrapleural vector followed by front line or second line chemotherapy 4-6 cycles every 21 days.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Malignant pleural mesothelioma (MPM) is a cancer for which there is no cure. The most effective combination chemotherapy, Pemetrexed (Alimta)/Cisplatin, has yielded overall response rates of up to 40%, but with improvements in overall median survival of only 3.5 months. Prior Phase I trials of intrapleural infusion (IP) of Ad.hIFN-beta (BG00001) were safe. The most recent trial of IP Ad.IFNalpha (SCH 721015) at a dose of 3e11 viral particles (vp) given three days apart was safe and well tolerated, and showed high levels of IFN in pleural fluid and serum. Our preclinical data modeling this proposed study suggest that two IP doses of Ad.IFN-alpha in combination with chemotherapy are well tolerated and markedly enhances efficacy. The purpose of the new study is to determine the safety of administrating intrapleural SCH 721015 (Ad.hIFN-alpha 2b) in combination with chemotherapy for the management of malignant pleural mesothelioma. This study will enroll subjects with pleural mesothelioma. Subjects will receive two fixed dosed of SCH 721015 followed by 4-6 cycles of chemotherapy. Subjects will require placement of a pleural catheter for administration of SCH 721015.

Some patients require a pleural catheter for control of pleural fluid while some will have it placed for research purpose only. Protocol participation is up to 15 years.

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • -Pathologically documented malignant mesothelioma
  • Must have evaluable disease by RECIST or Modified RECIST Criteria.
  • ECOG Performance status equal to or lesser than 1.
  • Must be at least 18 years of age.
  • Women of childbearing potential and men must use acceptable contraceptive methods during treatment.
  • Women of childbearing potential must have a negative serum or urine pregnancy test within 1 week prior to beginning treatment on this trial.
  • Must be able and willing to give written informed consent.
  • No radiotherapy and/or treatment with chemotherapeutic, cytotoxic, or immunologic agents within 4 weeks prior to infusion of the IFN-alpha vector.
  • Must have pleural tumor accessible for pleural catheter insertion. Patients with a previously inserted pleural catheter may enroll in the trial and can use the preexisting catheter for vector infusion as long as it is functional and has no evidence of local infection.
  • FEV1 equal to or lesser than 1 liter or 40% of predicted value (post-pleural drainage).
  • Acceptable hematologic value: granulocyte count equal to or lesser than 1,500/mm3, hemoglobin equal to or lesser than 9 g/dl, platelets equal to or lesser than 100,000/mm3
  • Acceptable liver function: bilirubin equal to or less than 1.5 x the upper limit of normal; ALT, AST, and alkaline phosphatase equal to or less than 2.0 x the upper limit of normal
  • Acceptable kidney function: creatinine less than 2.0 mg/dl (less than 1.5 mg/dl required for Cisplatin administration) or Creatinine clearance greater than 50.
  • Acceptable coagulation status: PT equal to or less than 1.5 x normal, PTT less than 1.5 x normal. However, patients on stable, chronic anti-coagulation therapy with therapeutic anti-coagulation levels will be allowed to enroll in the study.
  • Serum albumin must be greater than 2.5 g/dl
  • Must have an anti-adenoviral neutralizing antibody titer equal to or less than 1:1000. This will be measured by sub-investigators in the Thoracic Oncology Research Laboratory under standardized (but not GCP) conditions. Results must be known before performing any other research procedures.
  • Must have medical insurance coverage (or other means of payment) providing for standard medical interventions in clinical trial, including combination chemotherapy.

Exclusion Criteria:

  • Presence of significant pericardial effusion on baseline CT scan of the chest.
  • Documented immunodeficiency such as HIV infection.
  • Evidence of chronic active Hepatitis B (positive for HBsAg). Prior HBV exposure without evidence of chronic active Hepatitis B is not exclusionary.
  • Use of concurrent systemic steroids (greater than10 mg of prednisone per day), immunosuppressives, or any other medications that can directly or indirectly suppress the immune system.
  • Presence of any other life-threatening illness, such as unstable angina, severe oxygen dependence, significant chronic obstructive pulmonary disease (COPD), end stage liver or renal disease.
  • Rapidly re-accumulating,symptomatic malignant pleural effusion status-post thoracentesis or pleural catheter insertion that requires immediate mechanical or chemical pleurodesis for adequate palliation.
  • Presence of untreated brain metastases. Subjects with a prior history of brain metastases will have a CT or MRI scan of the brain to rule out activity.
  • Prior bone marrow or stem cell transplants -Female patients who are actively nursing are excluded.
  • Patients who have undergone any prior major surgery (excluding pleural catheter placement or infusaport insertion) less than 2 weeks prior to study enrollment.
  • Lack of medical insurance coverage (or other form of payment) for standard medical interventions, particularly combination chemotherapy.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: No prior chemotherapy
Intrapleural SCH 721015 (Ad.hIFN-α2b) instilled over 2-5 minutes on Days 1 and 4. Chemotherapy administered for 4 to 6 cycles Subjects with malignant pleural mesothelioma who have been previously untreated with chemotherapy
Drug: SCH 721015
Experimental: Patients with prior Pemetrexed-based chemotherapy
Intrapleural SCH 721015 (Ad.hIFN-α2b) instilled over 2-5 minutes on Days 1 and 4. Chemotherapy administered for 4 to 6 cycles Subjects with malignant pleural mesothelioma who have been previously treated with chemotherapy
Drug: SCH 721015

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To determine the safety of administering intrapleural SCH 721015, Ad.hIFN-alpha2b (Adenoviral-mediated Interferon-alpha) in combination with chemotherapy for the management of MPM.
Time Frame: On going throughout the conduct of the trial
No dose escalation is planned; however, dose de-escalation is possible should two or more DLTs be encountered in the first six patients treated. With 0 DLTs in 6 patients at a given dose, the upper exact 90% confidence limit on the DLT rate is 32%. With 1 DLT in 6 patients, the Bayesian upper 90% probability limit on the DLT rate is 58%. With 10 subjects per treatment group, we can identify with 90% power any unanticipated toxicity that has prevalence at least 20.6%; with n=15 per group, this figure decreases to 14.2%.
On going throughout the conduct of the trial

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To estimate objective response rates and distribution
Time Frame: On going throughout the conduct of the trial
Will estimate response rates by 95% confidence intervals, whose half-width will range from as low as 26% (if n=15 subjects are enrolled) to 32% (if n=10).
On going throughout the conduct of the trial
Time to Progression
Time Frame: On going throughout the conduct of the trial
Will summarize the distributions of time to progression (TTP) and time to death from any cause by Kaplan-Meier curves. In analyses of TTP, subjects who die without progression will be considered censored at the time of death. Further secondary goals include the evaluation of immunologic indicators of response, including systemic and intrapleural cytokines and cellular and humoral immune responses.
On going throughout the conduct of the trial

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Abramson Cancer Center of the University of Pennsylvania

Investigators

  • Principal Investigator: Andrew Haas, MD, PhD, University of Pennsylvania

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 27, 2010

Primary Completion (Actual)

October 14, 2013

Study Completion (Actual)

March 17, 2017

Study Registration Dates

First Submitted

May 6, 2010

First Submitted That Met QC Criteria

May 6, 2010

First Posted (Estimate)

May 7, 2010

Study Record Updates

Last Update Posted (Actual)

March 17, 2020

Last Update Submitted That Met QC Criteria

March 13, 2020

Last Verified

March 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UPCC 02510; 811318

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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