Paclitaxel, Polyglutamate Paclitaxel, or Observation in Treating Patients With Stage III or Stage IV Ovarian Epithelial, Peritoneal Cancer, or Fallopian Tube Cancer

PRIMARY OBJECTIVES:

I. To determine whether CT-2103 (polyglutamate paclitaxel) or paclitaxel, administered to
women with advanced ovarian, primary peritoneal or fallopian tube cancer who have attained a
clinically-defined complete response to primary platinum/taxane-based chemotherapy
(?consolidation/maintenance therapy?) will reduce the death rate, compared to re-treatment at
the time of documented disease progression.

II. To determine if, in this clinical setting, CT-2103 produces a more favorable toxicity
profile (with a particular focus on peripheral neuropathy as measured by the Gynecologic
Oncology Group [GOG] NTX4) and superior quality-of-life (as measured by the Functional
Assessment of Cancer Therapy-Ovarian [FACT-O]), compared to paclitaxel.

SECONDARY OBJECTIVES:

I. To explore the relationship between expression of several of the angiogenic markers and
overall survival or progression-free survival in patients randomized to CT-2103, paclitaxel,
or no treatment.

II. To assess the association among the various tissue and serum markers of angiogenesis, and
compare the ability of different combinations of these markers to predict patient outcome
including overall survival and progression-free survival in patients randomized to CT-2103,
paclitaxel, or no treatment.

III. To bank deoxyribonucleic acid (DNA) from whole blood for research and evaluate the
association between single nucleotide polymorphisms (SNPs) and measures of clinical outcome
including overall survival, progression-free survival and adverse events.

OUTLINE: Patients are randomized to 1 of 3 treatment arms.

ARM I: Patients receive polyglutamate paclitaxel intravenously (IV) over 10-20 minutes on day
1.

ARM II: Patients receive paclitaxel IV over 3 hours on day 1.

ARM III: Patients receive no further anticancer treatment until evidence of disease
progression.

In arms I and II, treatment repeats every 28 days for up to 12 courses in the absence of
disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 2 years and
then every 6 months for 10 years.

Inclusion Criteria:

- Patients with a histologic diagnosis of primary peritoneal carcinoma, or stage III or
IV epithelial ovarian or fallopian tube carcinoma, with either optimal (=< 1 cm
residual disease) or suboptimal residual disease following initial surgery; all
patients must have had appropriate surgery for ovarian, primary peritoneal or
fallopian tube carcinoma with appropriate tissue available for histologic evaluation
to confirm diagnosis and stage

- 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 tumor

- Adenocarcinoma not otherwise specified (NOS)

- Patients must have completed treatment within the past 12 weeks with at least 5 cycles
and not more than 8 cycles of a platinum (IV or intraperitoneal [IP]) and paclitaxel
or docetaxel-based combination chemotherapy and have no symptoms suggestive of
persistent cancer, normal (no evidence of cancer) computed tomography (CT) scan of the
abdomen/pelvis and normal cancer antigen 125 (CA-125) following this therapy

- Patients treated with neo-adjuvant platinum-taxane chemotherapy for a presumptive
diagnosis of stage III or IV epithelial ovarian, primary peritoneal or, fallopian
tube (by paracentesis, percutaneous biopsy or open biopsy) are eligible provided
that they have undergone interval abdominal surgery after at least one but no
more than six cycles of standard chemotherapy; such surgery must meet the same
criteria as for those undergoing up front surgery, including tissue diagnosis for
confirmation of primary tumor site and stage III or IV disease; also, patients
must have received at least two cycles after interval abdominal surgery

- Absolute neutrophil count >= 1,500/ul, equivalent to Common Toxicity Criteria (CTCAE
version [v]3.0) grade 1

- Platelet count >= 100,000/ul

- Creatinine =< 1.5 times institutional upper limit of normal (ULN), CTCAE v3.0 grade 1

- Bilirubin =< 1.5 times ULN, (CTCAE v3.0 grade 1)

- Serum glutamic oxaloacetic transaminase (SGOT) =< 2.5 times ULN (CTCAE v3.0 grade 1)

- Alkaline phosphatase =< 2.5 times ULN (CTCAE v3.0 grade 1)

- Neuropathy (sensory and motor) less than or equal to CTCAE v3.0 grade 1

- Gynecologic Oncology Group (GOG) performance status of 0, 1, or 2

- Patients must have signed an approved informed consent and Health Insurance
Portability and Accountability Act (HIPAA) authorization

- Patients must complete pre-entry assessments

Exclusion Criteria:

- Patients with a current diagnosis of epithelial ovarian or fallopian tube tumor of low
malignant potential (LMP) (Borderline carcinomas) are not eligible; patients with a
prior diagnosis of a low malignant potential tumor that was surgically resected and
who subsequently develop invasive adenocarcinoma are eligible, provided that they have
not received prior chemotherapy for their ovarian LMP tumor

- Germ cell tumors, sex cord-stromal tumors, carcinosarcomas, mixed mullerian tumors or
carcinosarcomas, metastatic carcinomas from other sites to the ovary and low malignant
potential tumors including so called micropapillary serous carcinomas are not eligible

- Patients who have received prior radiotherapy to any portion of the abdominal cavity
or pelvis are excluded; prior radiation for localized cancer of the breast, head and
neck, or skin is permitted, provided that it was completed more than 3 years prior to
registration, and the patient remains free of recurrent or metastatic disease

- Patients who have received investigational therapies, and/or biological therapies
(i.e. Bevacizumab or Erlotinib) for their epithelial ovarian, primary peritoneal or
fallopian tube cancers or for any other abdominal or pelvic tumor, are not excluded;
however, biologics cannot be continued concurrent with the GOG-012 maintenance
treatment (or observation); patients who have received prior chemotherapy for any
other abdominal or pelvic tumor (except as noted above) are excluded; patients may
have received prior adjuvant chemotherapy for localized breast cancer, provided that
it was completed more than 3 years prior to registration, and that the patient remains
free of recurrent or metastatic disease

- Patients with synchronous primary endometrial cancer, or a past history of primary
endometrial cancer, are excluded, unless all of the following conditions are met:

- Stage not greater than I-B

- Less than 3 mm invasion without vascular or lymphatic invasion

- No poorly differentiated subtypes, including papillary serous, clear cell, or
other Federation of Gynecology and Obstetrics (FIGO) Grade 3 lesions

- With the exception of non-melanoma skin cancer and other specific malignancies as
noted above, patients with other invasive malignancies who had (or have) any evidence
of the other cancer present within the last 5 years or whose previous cancer treatment
contraindicates this protocol therapy are excluded

- Patients with acute hepatitis, or known chronic hepatitis

- Patients with an active infection that requires antibiotics

- Patients with ongoing gastrointestinal bleeding requiring blood product support

- Patients whose circumstances at the time of entry onto the protocol would not permit
completion of study or required follow up

- Patients with unstable angina or those who have had a myocardial infarction within the
past six months; patients with evidence of abnormal cardiac conduction (e.g. bundle
branch block, heart block) are eligible if their disease has been stable for the past
six months

- Patients are excluded who have had prior therapy with CT-2103

- Patients with active bleeding or an unexplained prothrombin time (PT) or partial
thromboplastin time (PTT) > institutional upper limit normal (ULN)

- Patients who are pregnant or nursing are excluded; patients who may become pregnant
must practice an effective method of birth control