Erlotinib or Observation in Treating Patients Who Have Undergone First-Line Chemotherapy for Ovarian Cancer, Peritoneal Cancer, or Fallopian Tube Cancer

A Randomized, Multicenter, Phase III Study of Erlotinib Versus Observation in Patients With no Evidence of Disease Progression After First Line, Platinum-Based Chemotherapy For High-Risk Ovarian Epithelial, Primary Peritoneal, or Fallopian Tube Cancer

RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Sometimes after treatment, the tumor may not need additional treatment until it progresses. In this case, observation may be sufficient. It is not yet known whether erlotinib is more effective than observation after first-line chemotherapy in treating patients with ovarian cancer, peritoneal cancer, or fallopian tube cancer.

PURPOSE: This randomized phase III trial is studying erlotinib to see how well it works compared to observation in treating patients who have undergone first-line chemotherapy for ovarian cancer, peritoneal cancer, or fallopian tube cancer.

OBJECTIVES:

Primary

• Compare the benefits, in terms of progression-free survival, of maintenance therapy comprising erlotinib vs observation in patients with responding or stable disease after first-line, platinum-based chemotherapy for high-risk stage I or stage II-IV ovarian epithelial, primary peritoneal, or fallopian tube cancer.

Secondary

• Compare the overall survival of patients treated with these regimens.
• Determine the safety of erlotinib in these patients.
• Compare the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to disease stage (I-II vs III-IV), participating center, age (≤ 65 vs > 65), response to first-line therapy (no evidence of disease/complete response vs partial response vs stable disease), and first-line therapy (platinum-based vs platinum/taxane combination vs platinum-based triplet). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral erlotinib once daily for up to 2 years in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients undergo observation as per standard of care. Quality of life is assessed at baseline and then every 3 months for up to 2 years.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 830 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed ovarian epithelial, primary peritoneal, or fallopian tube cancer meeting 1 of the following criteria:

  • High-risk stage I disease, as defined by grade 3, aneuploid grade 1 or 2, or clear cell disease
  • Stage II, III, or IV disease

• Completed first-line therapy within the past 6 weeks

  • Received a platinum derivative (carboplatin or cisplatin) alone or in combination with other agents for 6-9 courses
  • Must have achieved complete response/no evidence of disease, partial response, or stabilization of disease after therapy

• No adenocarcinoma of unknown origin

• No known brain metastases or leptomeningeal disease

PATIENT CHARACTERISTICS:

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Platelet count ≥ 100,000/mm^3
• WBC ≥ 2,000/mm^3

Hepatic

• AST and ALT ≤ 2.5 times upper limit of normal (ULN) (≤ 5 times ULN in patients with known liver metastases)
• Bilirubin ≤ 1.5 times ULN
• Alkaline phosphatase ≤ 5 times ULN except in patients with known bone metastases
• PT and PTT ≤ 1.5 times ULN

Renal

• Creatinine ≤ 2 times ULN

Cardiovascular

• No myocardial infarction within past 6 months
• No second- or third-degree heart block without pacemaker

Gastrointestinal

• No active peptic ulcer disease
• No gastrointestinal tract disease that would interfere with ability to take oral medications, affect absorption, or require parenteral nutrition
• No uncontrolled inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis)

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No significant dermatologic disease
• No inflammatory changes to the surface of the eye
• No history of allergic reaction to compounds of similar chemical composition as erlotinib
• No other significant medical condition or neurologic or psychiatric disorder
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or cone-biopsied carcinoma in situ of the cervix
• No psychiatric illness or familial, geographic, or social situation that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior therapy targeting epidermal growth factor receptor
• No concurrent immunotherapy

Chemotherapy

• See Disease Characteristics
• See Surgery
• No concurrent chemotherapy

Endocrine therapy

• No concurrent hormonal therapy

Radiotherapy

• No prior radiotherapy unless completed more than 5 years ago AND outside the abdomen/pelvis

Surgery

• Interval debulking surgery after 3 courses of chemotherapy and second-look surgery at the end of chemotherapy allowed as per study EORTC-55971/NCIC OV13/Chorus

Other

• No other prior or concurrent investigational agents
• No other concurrent anticancer treatment
• Concurrent participation in study EORTC-55971/NCIC-OV13/Chorus allowed