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

Phase 0
18 Years
Open (Enrolling)

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Trial Information

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

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 will last about 6 months the
subjects will be followed up by telephone every 6 months for 15 years.

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

- 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

- 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.

Type of Study:


Study Design:

Primary Purpose: Treatment

Outcome Measure:

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.

Outcome Description:

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%.

Safety Issue:


Principal Investigator

Daniel H Sterman, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Abramson Cancer Center of the University of Pennsylvania


United States: Food and Drug Administration

Study ID:

UPCC 02510



Start Date:

April 2010

Completion Date:

Related Keywords:

  • Mesothelioma
  • Adult subjects with malignant pleural mesothelioma who present for first (front) line or second line chemotherapy,
  • Mesothelioma



Abramson Cancer Center of the University of PennsylvaniaPhiladelphia, Pennsylvania  19104-4283