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NCT01362790

SS1P and Pentostatin Plus Cyclophosphamide for Mesothelioma

Completed Phase 1, PHASE2 Results posted Last updated 6 June 2019
What this trial tests

Phase 1, PHASE2 trial testing Pentostatin in Mesothelioma in 55 participants. Completed in 7 August 2017.

Timeline
11 May 2011
Primary endpoint
3 August 2016
7 August 2017

Quick facts

Lead sponsorNational Cancer Institute (NCI)
PhasePhase 1, PHASE2
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment55
Start date11 May 2011
Primary completion3 August 2016
Estimated completion7 August 2017
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

National Cancer Institute (NCI)

Who can join

Adults 18 to 99, any sex, with Mesothelioma or Adenocarcinoma of Lung. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Response Assessment Primary · 52 months and 4 days

Response was assessed by the European Organization for Research and Treatment of Cancer (EORTC) modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Complete response (CR) is complete disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions. Progressive disease (PD) disease is at least a 20% increase in the sum of the LD of target lesions. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum L

Complete Response
GroupValue95% CI
Mesothelioma Pilot Phase Regimen A0
Mesothelioma Pilot Phase Regimen0
Phase 2 Peritoneal Mesothelioma Pilot Expansion Phase0
Phase 2 Pleural Mesothelioma Pilot Expansion Phase0
Phase 2 Pancreatic Adenocarcinoma Pilot Phase Regimen A0
Partial Response
GroupValue95% CI
Mesothelioma Pilot Phase Regimen A2
Mesothelioma Pilot Phase Regimen0
Phase 2 Peritoneal Mesothelioma Pilot Expansion Phase0
Phase 2 Pleural Mesothelioma Pilot Expansion Phase0
Phase 2 Pancreatic Adenocarcinoma Pilot Phase Regimen A0
Stable Disease
GroupValue95% CI
Mesothelioma Pilot Phase Regimen A5
Mesothelioma Pilot Phase Regimen6
Phase 2 Peritoneal Mesothelioma Pilot Expansion Phase6
Phase 2 Pleural Mesothelioma Pilot Expansion Phase6
Phase 2 Pancreatic Adenocarcinoma Pilot Phase Regimen A1
Progressive Disease
GroupValue95% CI
Mesothelioma Pilot Phase Regimen A3
Mesothelioma Pilot Phase Regimen1
Phase 2 Peritoneal Mesothelioma Pilot Expansion Phase1
Phase 2 Pleural Mesothelioma Pilot Expansion Phase3
Phase 2 Pancreatic Adenocarcinoma Pilot Phase Regimen A2
Count of Participants With SS1P Antibody Formation Primary · On last day of last dosing cycle, end of cycle 1 (day 30)

Development of antibodies following treatment with SS1P. The goal was to delay development of antibodies to SS1P so a patient could get a second cycle of therapy with SS1P.

GroupValue95% CI
Mesothelioma Pilot Phase Regimen A6
Mesothelioma Pilot Phase Regimen B2
Phase 2 Peritoneal Mesothelioma Pilot Expansion Phase3
Phase 2 Pleural Mesothelioma Pilot Expansion Phase7
Phase 2 Pancreatic Adenocarcinoma Pilot Phase Regimen A0
Phase 2 Lung Adenocarcinoma Pilot Expansion Phase Regimen A0
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 Primary · Date treatment consent signed to date off study, approximately 64 months and 26 days

Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one o

GroupValue95% CI
Mesothelioma Pilot Phase Regimen A11
Mesothelioma Pilot Phase Regimen B8
Phase 2 Peritoneal Mesothelioma Pilot Expansion Phase7
Phase 2 Pleural Mesothelioma Pilot Expansion Phase15
Phase 2 Pancreatic Adenocarcinoma Pilot Phase Regimen A4
Phase 2 Lung Adenocarcinoma Pilot Expansion Phase Regimen A0
Recommended Phase 2 Dose (RP2D) in Drug Lot FIL129J01 Primary · Days 1, 3, and 5 of a 21 day cycle

Should any 2 patients within the first 3 to 6 patients experience treatment limiting toxicity requiring cessation of treatment prior to the conclusion of the first cycle, the maximum tolerated dose will have been exceeded and patients will be enrolled to the next lower dose.

GroupValue95% CI
Meso., Peritoneal, Pleural & Pancreatic Regimen A25
Overall Survival Secondary · 36 months

The Kaplan-Meier was used to determine the probability of overall survival from on-study date until death or last follow-up (calculated from the date of study entry until the date of analysis).

GroupValue95% CI
Mesothelioma Pilot Phase Regimen A8.95.4 – 32.2
Mesothelioma Pilot Phase Regimen B11.21.0 – 13.0
Phase 2 Peritoneal Mesothelioma Pilot Expansion Phase29.33.4 – 29.3
Phase 2 Pleural Mesothelioma Pilot Expansion Phase4.22.0 – 7.9
Phase 2 Pancreatic Adenocarcinoma Pilot Phase Regimen A9.31.2 – 15.1
Progression-free Survival Secondary · 36 months

Defined as the time interval from the start of treatment to documented evidence of disease progression. Progressive disease is assessed by the European Organization for Research and Treatment of Cancer (EORTC) modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria, and is at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum on study LD (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 5mm

GroupValue95% CI
Meothelioma Pilot Phase Phase Regimen A11.81.6 – 13.6
Meothelioma Pilot Phase Regimen B8.80.6 – 13.0
Phase 2 Peritoneal Mesothelioma Pilot Expansion Phase8.91.8 – NA
Phase 2 Pleural Mesothelioma Pilot Expansion Phase3.91.6 – 6.4
Phase 2 Pancreatic Adenocarcinoma Pilot Phase Regimen A4.40.9 – 7.4
Duration of Response Secondary · up to 2.5 years

DOR is assessed by the European Organization for Research and Treatment of Cancer (EORTC) modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria and is measured from the time measurement criteria is met for complete response or partial response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Complete response is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-tar

GroupValue95% CI
Mesothelioma Pilot Phase Regimen A16.310.6 – 26.2
Count of Participants SS1P Cycles Received Following Onstudy Secondary · Cycles 1-6, up to 180 days

Here are the number of participants who had SS1P cycles during cycle 1-6.

SS1P 1 Cycle
GroupValue95% CI
Mesothelioma Pilot Phase Regimen A1
Mesothelioma Pilot Phase Regimen B3
Phase 2 Peritoneal Mesothelioma Pilot Expansion Phase0
Phase 2 Pleural Mesothelioma Pilot Expansion Phase5
Phase 2 Pancreatic Adenocarcinoma Pilot Phase Regimen A2
Phase 2 Lung Adenocarcinoma Pilot Expansion Phase Regimen A0
SS1P 2 Cycles
GroupValue95% CI
Mesothelioma Pilot Phase Regimen A8
Mesothelioma Pilot Phase Regimen B0
Phase 2 Peritoneal Mesothelioma Pilot Expansion Phase4
Phase 2 Pleural Mesothelioma Pilot Expansion Phase8
Phase 2 Pancreatic Adenocarcinoma Pilot Phase Regimen A1
Phase 2 Lung Adenocarcinoma Pilot Expansion Phase Regimen A0
SS1P 3 Cycles
GroupValue95% CI
Mesothelioma Pilot Phase Regimen A0
Mesothelioma Pilot Phase Regimen B3
Phase 2 Peritoneal Mesothelioma Pilot Expansion Phase0
Phase 2 Pleural Mesothelioma Pilot Expansion Phase1
Phase 2 Pancreatic Adenocarcinoma Pilot Phase Regimen A1
Phase 2 Lung Adenocarcinoma Pilot Expansion Phase Regimen A0
SS1P 4 Cycles
GroupValue95% CI
Mesothelioma Pilot Phase Regimen A1
Mesothelioma Pilot Phase Regimen B1
Phase 2 Peritoneal Mesothelioma Pilot Expansion Phase3
Phase 2 Pleural Mesothelioma Pilot Expansion Phase0
Phase 2 Pancreatic Adenocarcinoma Pilot Phase Regimen A0
Phase 2 Lung Adenocarcinoma Pilot Expansion Phase Regimen A0
SS1P 5 Cycles
GroupValue95% CI
Mesothelioma Pilot Phase Regimen A0
Mesothelioma Pilot Phase Regimen B1
Phase 2 Peritoneal Mesothelioma Pilot Expansion Phase0
Phase 2 Pleural Mesothelioma Pilot Expansion Phase1
Phase 2 Pancreatic Adenocarcinoma Pilot Phase Regimen A0
Phase 2 Lung Adenocarcinoma Pilot Expansion Phase Regimen A0
SS1P 6 Cycles
GroupValue95% CI
Mesothelioma Pilot Phase Regimen A1
Mesothelioma Pilot Phase Regimen B0
Phase 2 Peritoneal Mesothelioma Pilot Expansion Phase0
Phase 2 Pleural Mesothelioma Pilot Expansion Phase0
Phase 2 Pancreatic Adenocarcinoma Pilot Phase Regimen A0
Phase 2 Lung Adenocarcinoma Pilot Expansion Phase Regimen A0

Adverse events — posted to ClinicalTrials.gov

Time frame: Date treatment consent signed to date off study, approximately 64 months and 26 days.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Mesothelioma Pilot Phase Regimen A
Serious: 6/11 (55%)
Deaths: 5/11
Mesothelioma Pilot Phase Regimen B
Serious: 8/8 (100%)
Deaths: 8/8
Phase 2 Peritoneal Mesothelioma Pilot Expansion Phase
Serious: 3/7 (43%)
Deaths: 3/7
Phase 2 Pleural Mesothelioma Pilot Expansion Phase
Serious: 9/15 (60%)
Deaths: 9/15
Mesothelioma Positive Ca Dose De-escalation Pilot Regimen A
Serious: 1/8 (13%)
Deaths: 1/8
Phase 2 Pancreatic Adenocarcinoma Pilot Phase Regimen A
Serious: 1/4 (25%)
Deaths: 1/4
Phase 2 Lung Adenocarcinoma Pilot Expansion Phase Regimen A
Serious: 0
Deaths: 0

Serious adverse events (9 terms)

ReactionSystemMesothelioma Pilot Phase R…Mesothelioma Pilot Phase R…Phase 2 Peritoneal Mesothe…Phase 2 Pleural Mesothelio…Mesothelioma Positive Ca D…Phase 2 Pancreatic Adenoca…Phase 2 Lung Adenocarcinom…
Death NOSGeneral disorders
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specifyNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute kidney injuryRenal and urinary disorders
FeverGeneral disorders
Lung infectionInfections and infestations
Respiratory failureRespiratory, thoracic and mediastinal disorders
Atrial fibrillationCardiac disorders
HypoxiaRespiratory, thoracic and mediastinal disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
Other adverse events (131 terms — click to expand)

ReactionSystemMesothelioma Pilot Phase R…Mesothelioma Pilot Phase R…Phase 2 Peritoneal Mesothe…Phase 2 Pleural Mesothelio…Mesothelioma Positive Ca D…Phase 2 Pancreatic Adenoca…Phase 2 Lung Adenocarcinom…
HyperglycemiaMetabolism and nutrition disorders
Lymphocyte count decreasedInvestigations
HyponatremiaMetabolism and nutrition disorders
NauseaGastrointestinal disorders
HypoalbuminemiaMetabolism and nutrition disorders
AnemiaBlood and lymphatic system disorders
Edema limbsGeneral disorders
White blood cell decreasedInvestigations
FatigueGeneral disorders
HypophosphatemiaMetabolism and nutrition disorders
ConstipationGastrointestinal disorders
FeverGeneral disorders
HypotensionVascular disorders
Weight gainInvestigations
Activated partial thromboplastin time prolongedInvestigations
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInjury, poisoning and procedural complications
Creatinine increasedInvestigations
HyperkalemiaMetabolism and nutrition disorders
HypocalcemiaMetabolism and nutrition disorders
Platelet count decreasedInvestigations
AnorexiaMetabolism and nutrition disorders
DyspneaRespiratory, thoracic and mediastinal disorders
HypertensionVascular disorders
InsomniaPsychiatric disorders
VomitingGastrointestinal disorders
CoughRespiratory, thoracic and mediastinal disorders
DiarrheaGastrointestinal disorders
HypermagnesemiaMetabolism and nutrition disorders
HypomagnesemiaMetabolism and nutrition disorders
HypoxiaRespiratory, thoracic and mediastinal disorders
Neutrophil count decreasedInvestigations
Non-cardiac chest painMusculoskeletal and connective tissue disorders
Pleuritic painRespiratory, thoracic and mediastinal disorders
Sinus tachycardiaCardiac disorders
Back painMusculoskeletal and connective tissue disorders
ChillsGeneral disorders
DizzinessNervous system disorders
HypercalcemiaMetabolism and nutrition disorders
PainGeneral disorders

Most-reported serious reactions: Death NOS, Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify, Acute kidney injury, Fever, Lung infection, Respiratory failure, Atrial fibrillation, Hypoxia.

Data from ClinicalTrials.gov NCT01362790 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Mesothelin-Targeted CARs: Driving T Cells to Solid Tumors.
    Morello A, Sadelain M, Adusumilli PS. · · 2016 · cited 402× · PMID 26503962 · DOI 10.1158/2159-8290.cd-15-0583
  2. Mesothelin Immunotherapy for Cancer: Ready for Prime Time?
    Hassan R, Thomas A, Alewine C, Le DT, et al · · 2016 · cited 261× · PMID 27863199 · DOI 10.1200/jco.2016.68.3672
  3. Current advances and outlooks in immunotherapy for pancreatic ductal adenocarcinoma.
    Fan JQ, Wang MF, Chen HL, Shang D, et al · · 2020 · cited 179× · PMID 32061257 · DOI 10.1186/s12943-020-01151-3
  4. Major cancer regressions in mesothelioma after treatment with an anti-mesothelin immunotoxin and immune suppression.
    Hassan R, Miller AC, Sharon E, Thomas A, et al · · 2013 · cited 176× · PMID 24154601 · DOI 10.1126/scitranslmed.3006941
  5. Emerging molecular therapeutic targets for cholangiocarcinoma.
    Ilyas SI, Gores GJ. · · 2017 · cited 140× · PMID 28389139 · DOI 10.1016/j.jhep.2017.03.026
  6. Mesothelin as a biomarker for targeted therapy.
    Lv J, Li P, Li P. · · 2019 · cited 101× · PMID 31463062 · DOI 10.1186/s40364-019-0169-8
  7. In vitro and in vivo activity of the low-immunogenic antimesothelin immunotoxin RG7787 in pancreatic cancer.
    Hollevoet K, Mason-Osann E, Liu XF, Imhof-Jung S, et al · · 2014 · cited 92× · PMID 24928849 · DOI 10.1158/1535-7163.mct-14-0089-t
  8. Immunotoxins: the role of the toxin.
    Antignani A, Fitzgerald D. · · 2013 · cited 91× · PMID 23965432 · DOI 10.3390/toxins5081486

Verify or expand the search:

Other trials of Pentostatin

Trials testing the same drug.

Other recruiting trials for Mesothelioma

Currently open trials in the same condition.

Other National Cancer Institute (NCI) trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT01362790.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing