Phase 2 N=45 Treatment

SS1P and Pentostatin Plus Cyclophosphamide for Mesothelioma

Mesothelioma · Adenocarcinoma of Lung · Pancreatic Neoplasms

Bottom Line

View on ClinicalTrials.gov: NCT01362790 ↗

Enrolled (actual)

Serious AEs

52.8%

Results posted

Jun 2019

Primary outcome: Primary: Response Assessment — 0; 0; 0; 0 Participants

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Pentostatin (Drug); Cyclophosphamide (Drug); SS1(dsFv)PE38 - lot 073I0809 (Biological); SS1(dsFv)PE38 - lot FIL129J01 (Biological)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: National Cancer Institute (NCI)
Primary completion: Aug 2016

Outcome Measures

Outcome	Result	p-value
PRIMARY Response Assessment	0; 0; 0; 0; 0; 2	—
PRIMARY Count of Participants With SS1P Antibody Formation	6; 2; 3; 7; 0; 0	—
PRIMARY Count of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0) Who Were Administered SS1P and Pentostatin or Cyclophosphamide	11; 8; 7; 15; 4; 0	—
PRIMARY Recommended Phase 2 Dose (RP2D) in Drug Lot FIL129J01	25	—
SECONDARY Overall Survival	8.9; 11.2; 29.3; 4.2; 9.3	—
SECONDARY Progression-free Survival	11.8; 8.8; 8.9; 3.9; 4.4	—
SECONDARY Duration of Response	16.3	—

Summary

Background: * Malignant mesothelioma is a form of cancer that develops on the protective lining that covers the body's internal organs. It most often occurs on the lining of the lungs and chest wall or the lining of the abdomen. There is no known cure for malignant mesothelioma, so researchers are searching for new ways to treat it. * Mesothelin is a protein that is found in mesothelioma and other types of cancer cells. An experimental cancer drug called SS1P is designed to attack cells that have mesothelin while leaving healthy cells alone. Researchers want to test how effective SS1P is when it is given with pentostatin and cyclophosphamide. These drugs help suppress the immune system and may make the SS1P more effective. Objectives: - To study the effectiveness of SS1P plus two drugs that suppress the immune system to treat malignant mesothelioma. Eligibility: - Individuals at least 18 years of age who have malignant mesothelioma in the chest or abdomen. Design: * Participants will be screened with a physical exam, medical history, and blood tests. They will also have imaging studies. * The first treatment cycle will last 30 days. Up to three 21-day cycles of treatment will follow. * In the first cycle, participants will have pentostatin on days 1, 5, and 9. They will have cyclophosphamide on days 1 through 12. They will have SS1P on days 10, 12, and 14. * On the next three cycles, participants will have pentostatin on day 1.They will have cyclophosphamide on days 1 through 4. They will have SS1P on days 2, 4, and 6. * Participants will have frequent blood tests and other studies. They will receive all four cycles of treatment as long as there are no severe side effects. * Participants will have regular followup visits as directed by the study doctors.

Eligibility Criteria

INCLUSION CRITERIA: Mesothelioma Cohorts (Cohorts 1 and 2 Only)
Subjects must have histologically confirmed epithelial or biphasic mesothelioma not amenable to potentially curative surgical resection. However, patients with biphasic tumors that have a less than or equal to 50% sarcomatoid component will be excluded. The diagnosis will be confirmed by the Laboratory of Pathology / Center for Cancer Research (CCR) / National Cancer Institute (NCI).
Patients must have had at least one prior chemotherapy regimen, with the Food and Drug Administration (FDA) approved regimen of a platinum-based therapy in combination with pemetrexed being preferred unless there was a specific contraindication for an individual patient. There is no limit to the number of prior chemotherapy regimens received.
Total Bilirubin less than or equal to 1.5 X institutional upper limit of normal (ULN)

INCLUSION CRITERIA: Lung Adenocarcinoma Cohort (Cohort 3) Only

Subjects must have histologically confirmed advanced (Stage IIIB/IV) lung adenocarcinoma. The diagnosis will be confirmed by the Laboratory of Pathology/CCR/NCI.
Patients must have had at least one prior therapy for advanced disease [platinum containing chemotherapy or one of the approved targeted therapies (an approved estimated glomerular filtration rate (EGFR) tyrosine kinase inhibitor (TKI) for EGFR mutant tumors or crizotinib and ceritinib for ALK translocated tumors)]. There is no limit to the number of prior chemotherapy regimens received.
Mesothelin expression in at least 5% of cells as assessed in archival tumor tissue samples, determined by the immunohistochemistry (IHC) assay performed at Laboratory of Pathology / CCR / NCI. Archival samples must be available for eligibility.
Total Bilirubin less than or equal to 1.5 X institutional upper limit of normal (ULN)

INCLUSION CRITERIA: Pancreatic Cancer Cohort (Cohort 4) Only

Subjects with recurrent, locally advanced unresectable or metastatic adenocarcinoma of the pancreas. The diagnosis will be confirmed by the Laboratory of Pathology/CCR/NCI.
Patients must have had at least one prior chemotherapy for advanced disease. There is no limit to the number of prior chemotherapy regimens received.
Total Bilirubin less than or equal to 2 X institutional upper limit of normal (ULN)

INCLUSION CRITERIA: All Subjects

Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques or as >10 mm with spiral CT scan. See Section 11 for the evaluation of measurable disease.
Patients must not have had major surgery, radiation therapy, chemotherapy, biologic therapy (including any investigational agents), or hormonal therapy (other than replacement), within 4 weeks prior to entering the study and must have evidence of stable or progressive disease to be eligible.
Age greater than or equal to 18 years. Since the study diseases are extremely rare in children they are excluded from this study.
Performance status (Eastern Cooperative Oncology Group (ECOG)) less than or equal to 1
Patients must have adequate organ and marrow function (as defined below).
leukocytes less than or equal to 3,000/mm^3
absolute neutrophil count less than or equal to 1,500/mm^3
hemoglobin less than or equal to 9 g/dL
platelets less than or equal to 90,000/ mm^3
total bilirubin See guidelines for individual cohorts in sections 3.1.1.3, 3.1.2.4 and 3.1.3.3
Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase (SGOT))/alanine aminotransferase (ALT)(serum glutamic-pyruvic transaminase (SGPT)) less than or equal to 3 X institutional upper limit of normal (ULN) (5x if liver function test (LFT) elevations due to liver metastases)
creatinine less than or equal to 1.5 X institutional ULN

--creatinine clearance greater than or equal to 45 mL/min/1.73 m^2 for patients with creatinine levels

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Data sourced from ClinicalTrials.gov (NCT01362790). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.