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A Phase II Study of Erlotinib Plus Bevacizumab in the Treatment of Advanced Thymoma and Thymic Carcinoma

Phase 2
18 Years
Not Enrolling
Thymic Cancer, Thymoma

Thank you

Trial Information

A Phase II Study of Erlotinib Plus Bevacizumab in the Treatment of Advanced Thymoma and Thymic Carcinoma

We believe that both the EGFR pathway, as well as tumor angiogenesis play an important role
in the pathogenesis of thymic neoplasms. Our previous experience with the EGFR inhibitor
gefitinib showed a promising, though limited activity in this disease. We hypothesize that
combining the novel EGFR inhibitor erlotinib with bevacizumab will have a synergistic effect
on this tumor. We have selected the 15mg/kg q21 days of bevacizumab based on the data
published by Johnson DH et al, in which 99 patients were randomly assigned to bevacizumab
7.5 (n = 32) or 15 mg/kg (n = 35) plus carboplatin (area under the curve = 6) and paclitaxel
(200 mg/m2) every 3 weeks or carboplatin and paclitaxel alone (n = 32). The highest
response noted in the high-dose group (31.5%) and 28.1% in the lower dose bevacizumab arm.
There was also a trend to improved TTP and OS in the high dose arm, although the study
lacked sufficient power to make any definitive conclusions regarding a possible relationship
between dose and treatment effect. (105) The safety and efficacy of this dose and schedule
was confirmed by E4599 (43). Herbst et al have confirmed the safety of the combination of
erlotinib 150 mg/day orally plus bevacizumab 15 mg/kg in a published phase I/II trial (74)

This regimen has the potential to provide a new, effective therapy for this malignancy, as
well as teaching us important lessons about the biology of the disease. To this end, we
would also measure surrogate markers of angiogenesis, such as tumor VEGF expression, serum
VCAM-1 and bFGF, as well as urine VEGF. We would also determine tumor expression of
phosphorylated EGFR, and analyze the effect of known variant polymorphisms in the VEGF gene
on outcomes. We will test tumor samples for expression of EGFR by IHC and FISH to correlate
to response.

Inclusion Criteria:

- Histologically confirmed invasive, recurrent or metastatic thymoma or thymic
carcinoma not amenable to potentially curative therapy by surgery in the opinion of
the investigator. Original biopsy of tumor is sufficient for diagnoses unless
otherwise clinically indicated.

- Patients must have measurable disease per RECIST. Note: Any scans or x-rays used to
document measurable disease must be obtained within 28 days prior to registration.

- Patients must have had prior chemotherapy (no limit for prior regimens) for
metastatic disease.

- Patients must not have had any form of systemic anticancer therapy within 21 days
prior to being registered for protocol therapy.

- Patients receiving radiation therapy must have completed their radiation at least 21
days prior to being registered for protocol therapy, and toxicities due to radiation
must have recovered to ≤ grade 1 or baseline prior to registration. Previously
radiated area(s) must not be the only site of disease.

- Be at least 18 years of age at the time of consent.

- Patient's must have laboratory data as specified below within 14 days of registration
to study:

1. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times
upper limit of normal (ULN) (unless liver metastases are present, in which case
AST/ALT ≤ 5 times upper limit of normal will be acceptable).

2. Total bilirubin ≤ 1.5 mg/dl.

3. White blood cell (WBC) count > 3000/mm3

4. Absolute neutrophil count (ANC) ≥ 1500/mm3

5. Platelets ≥ 100,000/mm3

6. International normalized ration (INR) of prothrombin time ≤ 1.2, and aPTT no
more than 5 seconds longer than the ULN

7. Urine protein:creatinine ratio 1.0 at screening.

- Patients must not have prior history of malignancy in the past 5 years with the
exception of basal cell and squamous cell carcinoma of the skin. Other cancers with
low potential for metastasis, such as in situ cancers (e.g., Grade 1, TA TCC (low
grade superficial bladder cancer), colonic polyp with focus of adenocarcinoma) can
also be enrolled after approval from the study chair.

- No prior use of an EGFR inhibitor or anti-angiogenic agent.

- No use of an investigational agent within 30 days prior to registration for study

- Must not have any contraindications to the use of erlotinib or bevacizumab as per the
package labeling for either product.

- No uncontrolled hypertension ( e.g. > 150/100 mmHg pretreatment)

- No history of unstable angina.

- No history of New York Heart Association (NYHA) Grade II or greater congestive heart

- No history of myocardial infarction or angina pectoris/ anginal equivalent in the
last 6 months (the patient may be on anti-anginal medications if the symptoms have
been entirely controlled for greater than 6 months )within 6 months prior to
registration for protocol therapy.

- No history of stroke within 6 months prior to registration for protocol therapy.

- No clinically significant peripheral vascular disease.

- No evidence of bleeding diathesis or coagulopathy.(Low dose anticoagulant therapy to
maintain patency of a vascular access device is allowed).

- Patients must not have been using aspirin (>325 mg/day) or another nonsteroidal
anti-inflammatory medications known to inhibit platelet function daily within 10 days
prior to registration..

- Patients may not be taking the following drugs known to inhibit platelet function:
dipyridamole (Persantine), ticlopidine (Ticlid), clopidogrel (Plavix) and cilostazol

- No known evidence of central nervous system involvement or brain metastases. If
symptomatic must be confirmed by Head CT or Brain MRI within 6 weeks prior to being
registered for protocol therapy.

- No major surgical procedure, open biopsy, or significant traumatic injury within 28
days prior to registration for protocol therapy.

- No anticipation of need for major surgical procedure during the course of the study.

- No minor surgical procedures such as fine needle aspirations or core biopsies within
7 days prior to registration for protocol therapy.

- No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within 6 months prior to registration for protocol therapy.

- No serious, non-healing wound, ulcer, or bone fracture.

- No history of hemoptysis.

- No history of deep vein thrombosis or pulmonary embolism.

- No active infections.

Type of Study:


Study Design:

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

Outcome Measure:

To determine the objective response rate of the combination of erlotinib and bevacizumab in using RECIST.

Outcome Time Frame:

completion of study

Principal Investigator

Patrick J Loehrer, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Indiana University School of Medicine


United States: Food and Drug Administration

Study ID:

IUCRO-0148 / 0606-20



Start Date:

August 2006

Completion Date:

September 2007

Related Keywords:

  • Thymic Cancer
  • Thymoma
  • Thymoma
  • Thymic Cancer
  • Thymoma
  • Thymus Neoplasms



Indiana University Cancer CenterIndianapolis, Indiana  46202-5265