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A Phase I Trial of SS1 (dsFv) PE38 With Paclitaxel, Carboplatin, and Bevacizumab in Subjects With Unresectable Non-Small Cell Lung Adenocarcinoma

Phase 1
18 Years
Not Enrolling
Non-Small Cell Lung Cancer, Adenocarcinoma

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Trial Information

A Phase I Trial of SS1 (dsFv) PE38 With Paclitaxel, Carboplatin, and Bevacizumab in Subjects With Unresectable Non-Small Cell Lung Adenocarcinoma

- Treatment with platinum-based doublet chemotherapy results in a median survival of 7 to
10 months in patients with locally advanced or metastatic non-small cell lung cancer.

- In a randomized clinical trial of patients with non-squamous cell lung cancer,
treatment with carboplatin, paclitaxel and bevacizumab resulted in an objective
response rate of 35%, overall survival of 12.3 months compared to objective response
rate of 15%, overall survival of 10.3 months in patients treated with carboplatin and
paclitaxel alone.

- Mesothelin is a cell surface glycoprotein present on normal mesothelial cells that is
highly expressed in many human cancers including lung adenocarcinoma.

- SS1 (dsFv) PE38 is a recombinant anti-mesothelin immunotoxin that has undergone phase I
testing and is currently in clinical trials in combination with pemetrexed and
cisplatin for treatment of malignant pleural mesothelioma.

- Pre-clinical studies demonstrate increased anti-tumor activity of SS1 (dsFv) PE38 in
combination with chemotherapy and bevacizumab against mesothelin-expressing tumors.

Primary Objectives:

- This is a phase I study to determine a safe and tolerable phase II dose for the
combination of SS1 (dsFv) PE38 with paclitaxel, carboplatin and bevacizumab in patients with
advanced mesothelin-expressing lung adenocarcinoma.

Secondary Objectives:

- To assess response rate, duration of response, and progression-free survival (PFS).

- To characterize the pharmacokinetics (PK) of SS1 (dsFv) PE38 in combination with
chemotherapy and bevacizumab.

- Monitor serum mesothelin levels prior to and during chemotherapy.

- To identify T-cell epitopes responsible for neutralizing SS1 (dsFv) PE38 activity using
mononuclear cells obtained by apheresis.


- Histologically confirmed stage IIIB (malignant pleural effusion) or IV or recurrent
NSCLC (non-squamous cell, with mesothelin expression greater than or equal to 10% of
tumor cells by IHC).

- Adequate organ and bone marrow function.

- ECOG performance status of 0-1.


- Open label phase I trial.

Inclusion Criteria


1. Histologically or cytologically documented non-small cell lung adenocarcinoma
that is confirmed by the Laboratory of Pathology, NIH.

2. Mesothelin expression greater than or equal to 10% of tumor cells as determined
by immunohistochemistry (IHC) on tumor tissue specimens.

3. 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

4. Stage IIIB (malignant pleural effusion) or stage IV non-small cell lung cancer
or recurrent non-small cell lung cancer.

5. Age greater than or equal to 18 years (males or non-pregnant females).

6. Life expectancy of greater than 3 months.

7. ECOG performance status 0-1 (Karnofsky > 60%).

8. Serum Creatinine less than or equal to 1.5mg/dl.

9. Hemoglobin greater than or equal to 10.0g/dl.

10. Absolute neutrophil count greater than or equal to 1,500/m(3) and platelets
greater than or equal to 100,000/m(3).

11. AST/SGOT and ALT/SGPT less than or equal to 2.5 times ULN, total bilirubin less
than or equal to 1.5 times ULN (In patients with evidence of Gilberts disease,
elevated bilirubin should not be related to tumor or other liver diseases and
should be less than or equal 2 times upper limit of normal).

12. Urine protein to creatinine ratio < 1.0.

13. The ability to understand and the willingness to sign a written informed consent
document and the ability to comply with the requirements of the protocol. The
effects of SS1 (dsFv) PE38 on the developing human fetus are unknown. For this
reason and because immunotoxins are known to be teratogenic, women of
child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry
and for the duration of study participation and for at least 3 months
thereafter. Women of childbearing potential must have a negative pregnancy at
study enrollment. Should a woman become pregnant or suspect she is pregnant
while participating in this study, she should inform her treating physician

Inclusion of Women and Minorities:

Both men and women and members of all races and ethnic groups are eligible for this trial.


1. Squamous cell cancer or mixed tumors with any small cell element.

2. Tumor of any histology in close proximity to a major vessel or cavitation.

3. History of hemoptysis (bright red blood of teaspoon or more (greater than or equal
to 2.5 mL)) on one occasion unrelated to any diagnostic procedure within the past

4. Patients with CNS metastases.

5. History of uncontrolled hypertension, defined as blood pressure > 140/90 mmHg (NCI
CTEP Active Version of the CTCAE grade greater than or equal to 2) are excluded.
However, these patients will be eligible if the blood pressure is < 140/90 mmHg
after anti-hypertensive treatment.

6. Any of the following within 6 months prior to study enrollment: myocardial
infarction, unstable angina pectoris or uncontrolled angina pectoris,
coronary/peripheral artery bypass graft, NYHA class III or IV congestive heart
failure, clinically significant peripheral vascular disease (Grade II or greater).
History of stroke or transient ischemic attack within 6 months.

7. Psychiatric or neurologic illness that would limit compliance with study

8. Patients with serious illness or medical condition.

9. Severe active infection within 14 days requiring use of intravenous antibiotics
before beginning treatment.

10. Patients may not be receiving any other investigational agents.

11. History of an active malignancy unless curatively treated and risk of recurrence of <
5% at five years other than in situ carcinoma of the cervix, or non-melanomatous skin

12. Patients must not be on therapeutic anticoagulation, chronic daily treatment with
aspirin 325mg/day or non steroidal anti-inflammatory agents, or any agent known to
inhibit platelet function, within 10 days prior to day 1 on study. Low dose aspirin
81mg/day is allowed.

13. History of pulmonary embolism, deep venous thrombosis or other thromboembolic event
within 6 months.

14. Patients with a history of severe hypersensitivity reaction to compounds of similar
chemical or biologic composition to carboplatin, paclitaxel, bevacizumab or other
agents used in the study.

15. History of a major surgical procedure, open biopsy, or a significant traumatic injury
within 35 days prior to commencing treatment, or the anticipation of the need for a
major surgical procedure during the course of the study prior to the predetermined
date of tumor excision. Fine needle aspirations or core biopsies within 7 days prior
to commencing treatment are allowed.

16. History of abdominal fistula, gastrointestinal perforation, intra- abdominal abscess
or tracheo-esophageal fistula.

17. Non-healing wound or ulcer.

18. Evidence of coagulopathic disorder or hemorrhagic diathesis. INR greater than 1.5.

19. Pregnancy (positive pregnancy test) or active breast feeding.

20. Urine protein: creatinine ratio greater than or equal to 1.0 at screening.

21. HIV-positive patients on combination antiretroviral therapy are ineligible because of
the potential for pharmacokinetic interactions with chemotherapy. In addition, these
patients are at increased risk of lethal infections when treated with
marrow-suppressive therapy.

22. Significant laboratory abnormality requiring further investigation that may cause
undue risk for the subject's safety, inhibit protocol participation, or interfere
with interpretation of study results, and in the judgment of the investigator would
make the subject inappropriate for entry into this study.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Determined safe and tolerable phase 2 dose for combination of SS1 (dsFv) PE38 with paclitaxel, carboplatin, and bevacizumab.


United States: Federal Government

Study ID:




Start Date:

December 2009

Completion Date:

September 2011

Related Keywords:

  • Non-Small Cell Lung Cancer
  • Adenocarcinoma
  • Recombinant Immunotoxin
  • Monoclonal Antibody
  • Pseudomonas Exotoxin
  • Targeted Therapy
  • Lung Cancer
  • Non-Small Cell Lung Cancer
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms



National Institutes of Health Clinical Center, 9000 Rockville PikeBethesda, Maryland  20892