GOG-0127W: A Phase II Evaluation of ABT-888 (IND#77840, NSC #737664), Topotecan (NSC #609699) and Filgrastim or Pegfilgrastim in the Treatment of Persistent or Recurrent Squamous or Non-Squamos Cell Carcinoma of the Cervix
This is a phase II study and no randomization or placebo are involved. The intent of this protocol is to search for activity of new agents or drug combinations in patients with advanced or recurrent carcinoma of the cervix. There are no treatment comparisons involved and no known historical controls available. The study design will be primarily based on prior GOG experience in this disease entity. This will insure consistency in evaluation of response. Therapy plans demonstrating activity will later be compared and investigated in ensuing phase III studies.
ABT-888 10mg administered orally twice a day on days 1 to 5 of each cycle. Topotecan 0.6mg/m2 administered IV once daily on days 1 to 5 of each cycle. Each cycle of treatment repeats every 21 days until disease progression or adverse effects prohibit further therapy. All patients will receive filgrastim or pegfilgrastim beginning with cycle 1.
3.1 Eligible Patients:
3.11 Patients must have persistent or recurrent squamous cell carcinoma, adenosquamous carcinoma, adenocarcinoma or non-squamous cell carcinoma of the cervix with documented disease progression. Histological documentation of the original primary tumor is required via the pathology report.
3.12 All patients must have measurable disease as defined by RECIST 1.1. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be greater than or equal to10 mm when measured by CT, MRI or caliper measurement by clinical exam; or greater than or equal to 20 mm when measured by chest x-ray. Lymph nodes must be > 15 mm in short axis when measured by CT or MRI.
3.13 Patient must have at least one
* target lesion
* to be used to assess response on this protocol as defined by RECIST 1.1 (Section 8.1). Tumors within a previously irradiated field will be designated as
* lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy.
3.14 Patients must not be eligible for a higher priority GOG protocol, if one exists. In general, this would refer to any active GOG Phase III protocol or Rare Tumor protocol for the same patient population.
3.15 Patients must have a GOG Performance Status of 0, 1, or 2.
3.16 Recovery from effects of recent surgery, radiotherapy, or chemotherapy
3.161 Patients should be free of active infection requiring antibiotics.
3.162 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.
3.163 Any other prior therapy directed at the malignant tumor, including chemotherapy, biologic/targeted (non-cytotoxic) therapy and immunologic agents must be discontinued at least three weeks prior to registration. All side effects must have resolved to <= grade 1 or stabilized, prior to enrolling on this study. (9/26/11) (06/25/2012)
3.164 Any prior radiation therapy must be completed at least 4 weeks prior to registration. (9/26/11)
3.17 Prior therapy
3.171 Patients MUST have had one prior systemic chemotherapeutic regimen
for management of advanced, metastatic, or recurrent squamous or nonsquamous
cell carcinoma of the cervix. Chemotherapy administered concurrent with primary radiation is not counted as a systemic chemotherapy regimen (e.g.; weekly cisplatin). Adjuvant chemotherapy given following the completion of radiation therapy (or concurrent chemotherapy and radiation therapy) is not counted as a systemic chemotherapy regimen (e.g.; paclitaxel and carboplatin for up to 4 cycles). (9/26/11)
3.172 Patients who are registered during the safety lead-in portion of this protocol (see Section 5.4) are required to have prior pelvic radiation.
3.173 Patients must have NOT received more than one previous cytotoxic
3.172 Patients who are registered during the safety lead-in portion of this
protocol (see Section 5.4) are required to have prior pelvic radiation.
3.173 Patients must have NOT received more than one previous cytotoxic chemotherapy regimen (either with single or combination cytotoxic drug therapy).
3.174 Patients are allowed to have received, but are not required to have received, one additional non-cytotoxic regimen for management of recurrent or persistent disease according to the following definition:
Non-cytotoxic (biologic or cytostatic) agents include (but are not limited
to) monoclonal antibodies, cytokines, and small-molecule inhibitors of signal transduction.
3.174 Patients are allowed to receive, but are not required to receive, biologic/targeted (non-cytotoxic) therapy as part of their one prior systemic chemotherapeutic regimen. Patients are allowed to receive, but are not required to receive, biologic/targeted (non-cytotoxic) therapy for
management of recurrent or persistent disease. (06/25/2012)
3.18 Patients must have adequate:
3.181 Bone marrow function: Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl. Platelets greater than or equal to100,000/mcl.
3.182 Renal function: creatinine less than or equal to 1.5 x institutional upper limit normal (ULN).
3.183 Hepatic function: Bilirubin less than or equal to 1.5 x ULN. (AST) and ALT less than or equal to 3 x ULN and alkaline phosphatase less than or equal to 2.5 x ULN. (9/26/11)
3.184 Neurologic function: Neuropathy (sensory and motor) less than or equal to grade 1.
3.19 Patients must have signed an approved informed consent and authorization
permitting release of personal health information.
3.110 Patients must meet pre-entry requirements as specified in Section 7.0.
3.111 The effects of ABT-888 on the developing human fetus are unknown. For this reason and because other therapeutic agents or modalities used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control;
abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
3.112 Patients are at least 18 years of age.
3.113 Patients must have the ability to swallow pills whole.