GOG-0076HH: A Phase I/II Trial of Paclitaxel, Cisplatin and CTEP Supplied Agent ABT-888 (IND#77840, NSC#737664) in the Treatment of Advanced, Persistent, or Recurrent Carcinoma of the Cervix

Summary

This is a single-arm, Phase i/ ii study, and multi-center study, and no randomization is involved. The phase i/ii study is to estimate the MTD and recommend a phase ii dose of the combination of aBT-888 with cisplatin and paclitaxel, to examine the safety of the combination, and to estimate the activity of the combination at the recommended phase ii dose.

Primary endpoints:
Dose limiting toxicities in the first cycle of treatment [Phase i]
Frequency and severity of adverse effects as assessed by CTCae v 4
objective tumor response (complete or partial) [Phase ii]

Secondary endpoints:
Progression-free survival [Phase ii]
overall survival [Phase ii]

Participant Eligibility

Eligible Patients:
3.11 Patients must have primary stage IVB, recurrent or persistent squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix which is not amenable to curative treatment with surgery and/or radiation therapy. Histologic documentation of the original primary tumor is required via the pathology report.
3.12 All patients in the phase II portion must have measurable disease as defined by
RECIST 1.1 Measureable disease is defined as at least one lesion that can be
accurately measured in at least one dimension (longest dimension to be
recorded). Each lesion must be >= 10 mm when measured by CT, MRI or caliper
measurement by clinical exam; or >= 20 mm when measured by chest x-ray.
Lymph nodes must be >= 15 mm in short axis when measured by CT or MRI.
Measurable disease is not required for participation in the phase I portion of this study (See Section 3.1112).
3.13 Patients in the phase II portion 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
* non-target
* 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 have a GOG Performance Status of 0, 1, or 2.
3.15 Recovery from effects of recent surgery, radiotherapy or other therapy.
3.151 Patients should be free of active infection requiring antibiotics (with the exception of uncomplicated UTI).
3.152 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.
3.153 At least six weeks must have elapsed from the last administration of chemoradiotherapy, and at least three weeks must have elapsed from the last administration of radiation therapy alone. At least six weeks must have elapsed from the time of any major surgical procedure prior to randomization.
3.16 Patients must have adequate:
3.161 Bone marrow function: Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl. Platelets greater than or equal to100,000/mcl. Hemoglobin > 9 gm/dL.
3.162 Renal function: creatinine less than or equal to institutional upper limit
normal (ULN) or calculated creatinine clearance (Cockcroft-Gault) >= 60
ml/min.
3.163 Metabolic function: Calcium, Magnesium, Phosphate, and Potassium levels within institutional normal limits.
3.164 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.
3.165 Neurologic function: Neuropathy (sensory and motor) less than or equal to grade 1.
3.17 Patients must have signed an approved informed consent and authorization permitting release of personal health information.
3.18 Patients must meet pre-entry requirements as specified in Section 7.0.
3.19 Patients of childbearing potential must have a negative pregnancy test prior to the study entry and be practicing an effective form of contraception. 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 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.
3.110 Patients > 18 years of age.
3.111 Additional eligibility for the phase I portion of this study:
3.1111 All patients must have received prior chemoradiation.
3.1112 Patients do not need to have measurable disease.











Histologic documentation of the original primary tumor is required via the
pathology report.
3.12 All patients in the phase II portion must have measurable disease as defined by
RECIST 1.1 Measureable disease is defined as at least one lesion that can be
accurately measured in at least one dimension (longest dimension to be
recorded). Each lesion must be >= 10 mm when measured by CT, MRI or caliper
measurement by clinical exam; or >= 20 mm when measured by chest x-ray.
Lymph nodes must be >= 15 mm in short axis when measured by CT or MRI.
Measurable disease is not required for participation in the phase I portion
of this study (See Section 3.1112).
3.13 Patients in the phase II portion must have at least one 3.162 Renal function: creatinine less than or equal to institutional upper limit
normal (ULN) or calculated creatinine clearance (Cockcroft-Gault) >= 60
ml/min.
3.163 Metabolic function: Calcium, Magnesium, Phosphate, and Potassium
levels within institutional normal limits.
3.164 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.
3.165 Neurologic function: Neuropathy (sensory and motor) less than or equal
to grade 1.
3.17 Patients must have signed an approved informed consent and authorization
permitting release of personal health information.
3.18 Patients must meet pre-entry requirements as specified in Section 7.0.
3.19 Patients of childbearing potential must have a negative pregnancy test prior to
the study entry and be practicing an effective form of contraception. 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 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.
3.110 Patients > 18 years of age.
3.111 Additional eligibility for the phase I portion of this study:
3.1111 All patients must have received prior chemoradiation.
3.1112 Patients do not need to have measurable disease.