Combination Gene Transfer and Chemotherapy

NCT01119664 | Completed Phase 1 DMC

• 1 other identifier: UPCC 02510; 811318
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Mesothelioma

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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.

  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 Outcomes (2)

• To estimate objective response rates and distribution

  On going throughout the conduct of the trial

• Time to Progression

  On going throughout the conduct of the trial

Study Arms (2)

No prior chemotherapy

EXPERIMENTAL

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

Patients with prior Pemetrexed-based chemotherapy

EXPERIMENTAL

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

Interventions

SCH 721015 DRUG

No prior chemotherapy; Patients with prior Pemetrexed-based chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Presence of significant pericardial effusion on baseline CT scan of the chest.
• Documented immunodeficiency such as HIV infection.
• 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.

Sponsors & Collaborators

• Abramson Cancer Center at Penn Medicine: lead

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• Sterman DH, Alley E, Stevenson JP, Friedberg J, Metzger S, Recio A, Moon EK, Haas AR, Vachani A, Katz SI, Sun J, Heitjan DF, Hwang WT, Litzky L, Yearley JH, Tan KS, Papasavvas E, Kennedy P, Montaner LJ, Cengel KA, Simone CB 2nd, Culligan M, Langer CJ, Albelda SM. Pilot and Feasibility Trial Evaluating Immuno-Gene Therapy of Malignant Mesothelioma Using Intrapleural Delivery of Adenovirus-IFNalpha Combined with Chemotherapy. Clin Cancer Res. 2016 Aug 1;22(15):3791-800. doi: 10.1158/1078-0432.CCR-15-2133. Epub 2016 Mar 11.

  PMID: 26968202 BACKGROUND

MeSH Terms

Conditions

Mesothelioma

Condition Hierarchy (Ancestors)

Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial

Study Officials

• Andrew Haas, MD, PhD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2010
• First Posted: May 7, 2010
• Study Start: April 27, 2010
• Primary Completion: October 14, 2013
• Study Completion: March 17, 2017
• Last Updated: March 17, 2020

Record last verified: 2020-03

Locations

US (1)