This is an open-label Phase Ib dose-escalation study to determine the safety, tolerability,
and pharmacokinetics of PTC-596 when combined with and following conventional chemotherapy
and as maintenance therapy as a capsule (weight based dosing) and a tablet (fixed dosing) in
women with epithelial ovarian, fallopian tube or primary peritoneal cancer which is
previously untreated.
For all cohorts, the study drug PTC-596 will be orally administered prior to chemotherapy
(paclitaxel and carboplatin), twice a week of each 21-day cycle. Chemotherapy will be
administered on day 1 of each cycle by vein. Dose escalation levels for PTC-596 will occur
per protocol and doses may be de-escalated for management of toxicity. Patients will receive
a total of 3 cycles of PTC-596 and chemotherapy. Surgery will be performed within 6 weeks
after the last dose of Cycle 3. An additional 3-7 cycles of PTC-596 and chemotherapy
(carboplatin and paclitaxel) may be given as maintenance therapy for up to two years at the
discretion of the treating physician.
Inclusion Criteria:
- Histologically documented epithelial ovarian, primary peritoneal or fallopian tube
carcinoma or high grade serous adenocarcinoma, endometrioid adenocarcinoma,
undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma,or
adenocarcinoma not otherwise specified (N.O.S.)
- Newly diagnosed and be previously untreated
- Adequate bone marrow function, renal function, and hepatic function
- Baseline neuropathy (sensory and motor) less than or equal to Grade 1
- Free of active infection requiring parenteral antibiotics or a serious uncontrolled
medical illness or disorder within four weeks of study entry.
- Any hormonal therapy directed at the malignant tumor must be discontinued at least one
week prior to registration. Continuation of hormone replacement therapy is permitted.
- Have a performance status score of 0, 1, or 2 by Eastern Cooperative Group (ECOG)
criteria.
- Patients of childbearing potential must have a negative pregnancy test prior to the
study entry and be practicing an effective form of contraception. If applicable,
patients must discontinue breastfeeding prior to study entry.
Exclusion Criteria:
- Prior treatment with PTC596 or standard of care drugs (cis- or carboplatin or
paclitaxel.
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to PTC596 or other agents used in this study.
- Have a clinical requirement for ongoing systemic immunosuppressive therapy such as
chronic steroid use not related to chemotherapy administration.
- Receiving treatment for active autoimmune disease including systemic lupus
erythematosus, multiple sclerosis, inflammatory bowel disease and rheumatoid
arthritis.
- History of other invasive malignancies, with the exception of non-melanoma skin cancer
and other specific malignancies within the last three years. Patients are also
excluded if their previous cancer treatment contraindicates this protocol therapy.
Patients with concomitant endometrial cancer diagnosed at the time of their ovarian
cancer are allowed to participate if the endometrial cancer is FIGO stage IB or less.
- Prior radiotherapy to any portion of the abdominal cavity or pelvis. Prior radiation
for localized cancer of the breast, head and neck, or skin is permitted if completed
more than three years prior to registration and the patient remains free of recurrent
or metastatic disease.
- Prior chemotherapy for any abdominal or pelvic tumor. Patients may have received prior
adjuvant chemotherapy for localized breast cancer, provided that it was completed
three years prior to registration, and that the patient remains free of recurrent or
metastatic disease.
- Known active hepatitis, ongoing systemic bacterial, fungal, or viral infection; known
human immunodeficiency virus (HIV) infection or acquired-immunodeficiency syndrome
(AIDS)-related illness.
- Have concurrent severe medical problems unrelated to the malignancy that would
significantly limit full compliance with the study or expose the patient to extreme
risk or decreased life expectancy.
- Have childbearing potential but not practicing adequate contraception, or pregnant, or
breastfeeding.
- History or active CNS disease, including primary brain tumor, seizures not controlled
with standard medical therapy, any brain metastases, or history of cerebrovascular
accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage
within six months prior to study treatment.
- Concomitant therapy with any of the following: other non-study cytotoxic chemotherapy;
other investigational therapies.
- Prior bone marrow/hematopoietic stem cell transplantation
- Use of an investigational drug within 4 weeks of dosing in the current study
- History of major surgical procedure within 28 days prior to start of study treatment
- Presence of history of moderate to severe pulmonary dysfunction (e.g., moderate/severe
chronic obstructive pulmonary disease, post-pneumoectomy, shortness of breath with
limited exertion).
