Erlotinib Plus Carboplatin and Paclitaxel in Ovarian Carcinoma

PRIMARY OBJECTIVES:

I. To establish whether the addition of OSI-774 (Tarceva) to the combination of paclitaxel
and carboplatin encourages pathologic complete response (pCR) rates in patients with Stage
III optimally cytoreduced (stratum 1) and Stage III suboptimally cytoreduced or Stage IV
(stratum 2) ovarian, primary peritoneal or fallopian tube carcinomas when used as front line
therapy.

II. To determine the degree and type of toxicity associated with this combined regimen.

SECONDARY OBJECTIVES:

I. To establish baseline epidermal growth factor receptor (EGFR), truncated EGFR (EGFRvIII),
phosphorylated EGFR (pEGFR) and related signal transduction pathway protein expression
levels (such as the mitogen activated protein kinase p-ERK, AKT phosphorylation and
Her2/neu) in tumor samples obtained pretreatment, and to correlate these with achieving pCR.

II. To describe changes in EGFR, EGFRvIII, pEGFR expression levels and other related signal
transduction pathway expression occurring during treatment with OSI-774 in combination with
chemotherapy.

III. To determine the effect of the addition of OSI-774 (Tarceva) to the combination of
paclitaxel and carboplatin on progression-free interval in patients with Stage III optimally
cytoreduced (stratum 1) and Stage III suboptimally cytoreduced or Stage IV (stratum 2)
ovarian or primary peritoneal carcinomas when used as front line therapy.

IV. To determine the tolerability of twelve months of maintenance treatment with OSI-774 for
patients achieving pCR, and to measure the progression-free interval for this population.

V. To document cutaneous effects of OSI 774 prospectively, and to correlate the degree of
skin rash with clinical and translational endpoints.

OUTLINE: This is a non-randomized study. Patients are stratified according to disease stage
(stage III with optimal residual disease vs stage III with suboptimal residual disease or
stage IV).

Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1.
Patients also receive oral erlotinib daily. Treatment repeats every 21 days for up to 6
courses in the absence of disease progression or unacceptable toxicity. Patients who achieve
a pathologic complete response, those initially suboptimally debulked with a response, and
patients who elect not to undergo surgical reassessment but who achieve a complete clinical
response receive maintenance erlotinib for an additional 12 months.

Inclusion Criteria:

- Patients with a histologic diagnosis of primary peritoneal carcinoma, fallopian tube
epithelial ovarian carcinoma, Stage III with either greater than 1 cm (suboptimal)
residual disease following initial surgery, or Stage IV; all patients must either
have had appropriate surgery for ovarian, fallopian tube or peritoneal carcinoma with
appropriate tissue available for histologic evaluation to confirm diagnosis and stage
or must be unresectable at time of diagnosis (to be determined by gynecological
oncologist); cytology alone is not adequate

- Patients with the following histologic epithelial cell types are eligible: Serous
adenocarcinoma, endometrioid adenocarcinoma, mucinous adenocarcinoma,
undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma,
transitional cell carcinoma, malignant Brenner's Tumor, or adenocarcinoma not
otherwise specified (NOS)

- Patients must begin chemotherapy on this study no more than twelve weeks
postoperatively

- Patients must not have received chemotherapy within five years prior to enrollment

- ECOG performance status =< 2 (Karnofsky >= 60%)

- Absolute neutrophil count >= 1,500/uL

- Platelets >= 100,000/uL

- Total bilirubin =< 1.5 x institutional upper limit of normal

- AST(SGOT)/ALT(SGPT) =< 2.5 x institutional upper limit of normal

- Creatinine =< 1.5 x institutional upper limit of normal OR creatinine clearance >= 60
mL/min/1.73 m^2 for patients with creatinine levels above institutional normal

- Neuropathy (sensory and motor) =< CTC grade 1

- No medical contraindications to planned regimen

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- Patients who have had courses of chemotherapy within the five years prior to entering
the study

- Patients may not be receiving any other investigational agents

- Patients with known brain metastases should be excluded from this clinical trial
because of their poor prognosis and because they often develop progressive neurologic
dysfunction that would confound the evaluation of neurologic and other adverse events

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition OSI-774 or other agents used in the study

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- Pregnant women are excluded from this study because OSI-774 has the potential for
teratogenic or abortifacient effects; because there is an unknown but potential risk
for adverse events in nursing infants secondary to treatment of the mother with
OSI-774, breastfeeding should be discontinued if the mother is treated with OSI-774;
these potential risks may also apply to other agents used in this study

- Because patients with immune deficiency are at increased risk of lethal infections
when treated with marrow-suppressive therapy, HIV-positive patients receiving
combination anti-retroviral therapy are excluded from the study because of possible
pharmacokinetic interactions with OSI-774 or other agents administered during the
study; appropriate studies will be undertaken in patients receiving combination
anti-retroviral therapy when indicated