Erlotinib in Treating Patients With Persistent or Recurrent Cancer of the Cervix

National Cancer Institute (NCI)

Status and phase

Completed

Phase 2

Conditions

Cervical Squamous Cell Carcinoma

Recurrent Cervical Cancer

Treatments

Drug: erlotinib hydrochloride

Other: laboratory biomarker analysis

Study type

Interventional

Funder types

NIH

Identifiers

NCT00031993

U10CA027469 (U.S. NIH Grant/Contract)

CDR0000069247 (Registry Identifier)

NCI-2012-02457

GOG-0227D

Details and patient eligibility

About

This phase II trial is studying erlotinib to see how well it works in treating patients with persistent or recurrent cancer of the cervix. Biological therapies such as erlotinib may interfere with the growth of tumor cells and slow the growth of the tumor

Full description

PRIMARY OBJECTIVES:

I. To evaluate the antitumor cytostatic activity of OSI-774 as measured by the probability of surviving progression-free for at least 6 months in patients with persistent or recurrent squamous cell carcinoma of the cervix.

II. To determine the nature and degree of toxicity of OSI-774 in this cohort of patients.

SECONDARY OBJECTIVES:

I. To determine the partial and complete response rates in patients with squamous cell carcinoma of the cervix receiving OSI-774.

II. To determine the duration of progression-free survival and overall survival within this patient population treated with OSI-774.

III. Assess the effects of prognostic factors: initial performance status and age.

TERTIARY OBJECTIVES:

I. To determine epidermal growth factor receptor (EGFR) and p110 truncated EGFR (p110 sEGFR) isoform expression levels in primary tumors, and from tumor samples obtained pretreatment and following four weeks of therapy to determine tumor response (or resistance) to OSI-774 inhibition of the EGFR tyrosine kinase.

II. To correlate EGFR and p110sEGFR expression levels with either MAPK or AKT phosphorylation status in the same tissue samples obtained pretreatment and following four weeks of drug treatment to determine downstream effects with response to OSI-774 inhibition of EGFR.

III. To determine whether pretreatment serum p110 sEGFR concentrations are a useful prognostic indicator and whether altered and/or sEGFR concentrations are useful indicators of therapeutic responsiveness, time to progression, and overall survival in cervical carcinoma patients.

OUTLINE: This is a multicenter study.

Patients receive oral erlotinib once daily for 4 weeks. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years and then every 6 months for 3 years.

Enrollment

51 patients

Sex

Female

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

Histologically confirmed squamous cell carcinoma (SCC) of the cervix
- Persistent or recurrent progressive disease
- At least 1 prior systemic chemotherapy regimen for management of advanced, metastatic, or recurrent SCC of the cervix is required
  - Chemotherapy administered as a radiosensitizer in conjunction with radiotherapy does not count as a systemic chemotherapy regimen
At least 1 unidimensionally measurable target lesion
- At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan
- Lesions within a previously irradiated field are considered nontarget lesions unless disease progression or persistence is confirmed ≥ 90 days after completion of radiotherapy
Tumor accessible for repeat needle biopsy
Ineligible for a higher priority Gynecologic Oncology Group (GOG) protocol (any active GOG phase III protocol for the same patient population)
Performance status - GOG 0-2 (for patients who have received only 1 prior regimen)
Performance status - GOG 0-1 (for patients who have received 2 prior regimens)
Platelet count at least 100,000/mm^3
Absolute neutrophil count at least 1,500/mm^3
Bilirubin no greater than upper limit of normal (ULN)
SGOT no greater than 2.5 times ULN
Alkaline phosphatase no greater than 2.5 times ULN
Creatinine no greater than 1.5 times ULN
No symptomatic congestive heart failure
No unstable angina pectoris
No cardiac arrhythmia
No abnormalities of the cornea (e.g., dry eye syndrome or Sjogren's syndrome)
No congenital abnormalities (e.g., Fuch's dystrophy)
No abnormal slit-lamp examination using a vital dye (e.g., fluorescein or Bengal-Rose)
No abnormal corneal sensitivity test (Schirmer test or similar tear production test)
No other invasive malignancy within the past 5 years except nonmelanoma skin cancer
No uncontrolled concurrent illness
No ongoing or active infection requiring IV antibiotics
No psychiatric illness or social situation that would preclude study compliance
No grade 2 or greater sensory or motor neuropathy
No prior allergic reactions attributed to compounds of similar chemical or biological composition to erlotinib
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
HIV negative
At least 3 weeks since prior immunologic therapy for SCC of the cervix
One additional prior cytotoxic chemotherapy regimen for recurrent or persistent disease allowed
At least 3 weeks since prior chemotherapy for SCC of the cervix and recovered
No prior non-cytotoxic chemotherapy for recurrent or persistent disease
At least 3 weeks since prior hormonal therapy for SCC of the cervix
At least 3 weeks since prior radiotherapy for SCC of the cervix and recovered
Recovered from recent prior surgery
At least 3 weeks since other prior therapy for SCC of the cervix
No prior epidermal growth factor receptor-targeting therapies
No prior anticancer treatment that would preclude study participation
No other concurrent investigational or commercial agents or therapies for SCC of the cervix