Cervical AdenocarcinomaPhase 2NCT01266447
Veliparib, Topotecan Hydrochloride, and Filgrastim or Pegfilgrastim in Treating Patients With Persistent or Recurrent Cervical Cancer
A Phase 2 study testing Filgrastim, Laboratory Biomarker Analysis and Pegfilgrastim in people with Cervical Adenocarcinoma and Cervical Adenosquamous Carcinoma, run by National Cancer Institute (NCI) at 78 sites in United States.
Trial summary
This phase II clinical trial is studying the how well veliparib, topotecan hydrochloride, and filgrastim or pegfilgrastim work in treating patients with persistent or recurrent cervical cancer. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Cervical Adenocarcinoma, Cervical Adenosquamous Carcinoma, Cervical Small Cell Carcinoma
- What is being tested?
- Filgrastim, Laboratory Biomarker Analysis and Pegfilgrastim
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 78 sitesUnited States
- Study dates
- Feb 2011to Jan 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
- 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 >= 10 mm when measured by computed tomography (CT), magnetic resonance imaging (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
- Patient must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST 1.1; 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
- Patients must not be eligible for a higher priority Gynecologic Oncology Group (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
- Patients must have a GOG performance status of 0, 1, or 2
- Recovery from effects of recent surgery, radiotherapy, or chemotherapy
Show all 26Show fewer
- Patients should be free of active infection requiring antibiotics
- 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
- 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
- Any prior radiation therapy must be completed at least 4 weeks prior to registration
- Patients MUST have had one prior systemic chemotherapeutic regimen for management of advanced, metastatic, or recurrent squamous or non-squamous 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)
- Patients who are registered during the safety lead-in portion of this protocol are required to have prior pelvic radiation
- Patients must have NOT received more than one previous cytotoxic chemotherapy regimen (either with single or combination cytotoxic drug therapy)
- 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
- Patients MUST not be eligible for further curative intent surgical or pelvic radiation treatment for management of recurrent or persistent disease as determined by treating physicians
- Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl
- Platelets greater than or equal to 100,000/mcl
- Creatinine less than or equal to 1.5 x institutional upper limit normal (ULN)
- Bilirubin less than or equal to 1.5 x ULN
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 3 x ULN
- Alkaline phosphatase less than or equal to 2.5 x ULN
- Neuropathy (sensory and motor) less than or equal to grade 1
- Patients must have signed an approved informed consent and authorization permitting release of personal health information
- Patients must meet pre-entry requirements
- 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
- Patients must have the ability to swallow pills whole
Who cannot join
- Patients are excluded who have had prior therapy with ABT-888 (veliparib), poly (ADP)-ribose polymerase inhibitors, or topotecan
- Patient with a history of other invasive malignancies, with the exception of non-melanoma skin cancer and other specific malignancies are excluded if there is any evidence of other malignancy being present within the last three years; patients are also excluded if their previous cancer treatment contraindicates this protocol therapy
- Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis OTHER THAN for the treatment of cervical cancer within the last three years are excluded; prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease
- Patients who have received prior chemotherapy for any abdominal or pelvic tumor OTHER THAN for the treatment of cervical cancer within the last three years are excluded; patients may have received prior adjuvant chemotherapy for cancer, provided that it was completed more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease
- Patients with seizures or history of seizures are ineligible
- Patients with history or evidence upon physical examination of central nervous system (CNS) disease, including primary brain tumor, any CNS metastases, or history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months of the first date of treatment on this study, are ineligible; patients with CNS metastases must be stable for > 3 months after treatment and off steroid treatment prior to study enrollment
Trial locations and contacts
78 sites in 1 country.
78 sites in 1 country
United States78 sites
Abington Memorial Hospital
Abington, Pennsylvania, 19001
Southwest Gynecologic Oncology Associates Inc
Albuquerque, New Mexico, 87106
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87106
Saint Joseph Mercy Hospital
Ann Arbor, Michigan, 48106-0995
Michigan Cancer Research Consortium CCOP
Ann Arbor, Michigan, 48106
University of Colorado Cancer Center - Anschutz Cancer Pavilion
Aurora, Colorado, 80045
University Medical Center Brackenridge
Austin, Texas, 78701
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
PeaceHealth Medical Group PC
Bellingham, Washington, 98226
Saint Alphonsus Cancer Care Center-Boise
Boise, Idaho, 83706
Harrison HealthPartners Hematology and Oncology-Bremerton
Bremerton, Washington, 98310
Harrison Medical Center
Bremerton, Washington, 98310
State University of New York Downstate Medical Center
Brooklyn, New York, 11203
Cooper Hospital University Medical Center
Camden, New Jersey, 08103
Case Western Reserve University
Cleveland, Ohio, 44106
Riverside Methodist Hospital
Columbus, Ohio, 43214
Parkland Memorial Hospital
Dallas, Texas, 75235
Zale Lipshy University Hospital
Dallas, Texas, 75235
Clements University Hospital
Dallas, Texas, 75390
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390
Oakwood Hospital and Medical Center
Dearborn, Michigan, 48124
Decatur Memorial Hospital
Decatur, Illinois, 62526
Saint John Hospital and Medical Center
Detroit, Michigan, 48236
Providence Regional Cancer Partnership
Everett, Washington, 98201
Hurley Medical Center
Flint, Michigan, 48502
Genesys Regional Medical Center
Grand Blanc, Michigan, 48439
Smilow Cancer Hospital Care Center at Saint Francis
Hartford, Connecticut, 06105
Sudarshan K Sharma MD Limted-Gynecologic Oncology
Hinsdale, Illinois, 60521
Indiana University/Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242
Allegiance Health
Jackson, Michigan, 49201
University of Mississippi Medical Center
Jackson, Mississippi, 39216
Borgess Medical Center
Kalamazoo, Michigan, 49001
Bronson Methodist Hospital
Kalamazoo, Michigan, 49007
West Michigan Cancer Center
Kalamazoo, Michigan, 49007
Sparrow Hospital
Lansing, Michigan, 48912
Women's Cancer Center of Nevada
Las Vegas, Nevada, 89169
Saint Mary Mercy Hospital
Livonia, Michigan, 48154
North Shore University Hospital
Manhasset, New York, 11030
Lake University Ireland Cancer Center
Mentor, Ohio, 44060
Skagit Valley Hospital Regional Cancer Care Center
Mount Vernon, Washington, 98273
D N Greenwald Center
Mukwonago, Wisconsin, 53149
The Hospital of Central Connecticut
New Britain, Connecticut, 06050
Long Island Jewish Medical Center
New Hyde Park, New York, 11040
North Shore-LIJ Health System/Center for Advanced Medicine
New Hyde Park, New York, 11040
Oconomowoc Memorial Hospital-ProHealth Care Inc
Oconomowoc, Wisconsin, 53066
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868
Florida Hospital Orlando
Orlando, Florida, 32803
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
Saint Joseph Mercy Oakland
Pontiac, Michigan, 48341
Saint Joseph Mercy Port Huron
Port Huron, Michigan, 48060
Harrison HealthPartners Hematology and Oncology-Poulsbo
Poulsbo, Washington, 98370
Women and Infants Hospital
Providence, Rhode Island, 02905
Virginia Commonwealth University/Massey Cancer Center
Richmond, Virginia, 23298
Saint Mary's of Michigan
Saginaw, Michigan, 48601
Memorial University Medical Center
Savannah, Georgia, 31404
Pacific Gynecology Specialists
Seattle, Washington, 98104
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109
Seattle Cancer Care Alliance
Seattle, Washington, 98109
Group Health Cooperative-Seattle
Seattle, Washington, 98112
Swedish Medical Center-First Hill
Seattle, Washington, 98122-4307
Northwest Hospital
Seattle, Washington, 98133
University of Washington Medical Center
Seattle, Washington, 98195
Olympic Medical Cancer Care Center
Sequim, Washington, 98384
Cancer Care Northwest - Spokane South
Spokane, Washington, 99202
Rockwood Cancer Treatment Center-DHEC-Downtown
Spokane, Washington, 99204
Memorial Medical Center
Springfield, Illinois, 62781
Cancer Research for the Ozarks NCORP
Springfield, Missouri, 65804
Mercy Hospital Springfield
Springfield, Missouri, 65804
CoxHealth South Hospital
Springfield, Missouri, 65807
MultiCare Tacoma General Hospital
Tacoma, Washington, 98405
Saint Joseph Medical Center
Tacoma, Washington, 98405
Scott and White Memorial Hospital
Temple, Texas, 76508
Oklahoma Cancer Specialists and Research Institute-Tulsa
Tulsa, Oklahoma, 74146
Providence Saint Mary Regional Cancer Center
Walla Walla, Washington, 99362
Waukesha Memorial Hospital
Waukesha, Wisconsin, 53188
Wenatchee Valley Hospital and Clinics
Wenatchee, Washington, 98801
About this study
Official title: A Phase II Evaluation of ABT-888 (NCI Supplied Agent: ABT-888, NSC #737664), Topotecan (NSC # 609699) and Filgrastim or Pegfilgrastim in the Treatment of Persistent or Recurrent Squamous or Non-squamous Cell Carcinoma of the Cervix
This phase II clinical trial is studying the how well veliparib, topotecan hydrochloride, and filgrastim or pegfilgrastim work in treating patients with persistent or recurrent cervical cancer. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as topotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by blocking them from dividing. Giving veliparib with chemotherapy may kill more tumor cells. Filgrastim or pegfilgrastim may cause the body to make more blood cells and help it recover from the side effects of chemotherapy.
Read the detailed description
PRIMARY OBJECTIVES:
- To estimate the antitumor activity (objective response rate by RECIST 1.1) of ABT-888 (veliparib) 10 mg administered orally twice a day on days 1 to 5 with topotecan (topotecan hydrochloride) 0.6 mg/m^2 administered IV once daily on days 1 to 5 of each cycle in patients with persistent or recurrent carcinoma of the cervix.
II. To determine the nature and degree of toxicity of ABT-888 and topotecan in patients with persistent or recurrent carcinoma of the cervix.
SECONDARY OBJECTIVES:
- To determine the duration of progression-free survival and overall survival.
TERTIARY OBJECTIVES:
- To determine whether evidence of an interaction exists between study treatments and tumor expression of poly(ADP-ribos)ylation of E2 protein, E6/E7 proteins, and p53R2 in relation to progression-free and overall survival or metastasis. (Translational) II. To explore the association between methylation of FanCF and BRCA in pre-treatment tumor samples and pre- and post-treatment biopsy samples and response, progression-free and overall survival of patients, and/or metastasis. (Translational)
OUTLINE:
Patients receive veliparib orally (PO) twice daily and topotecan hydrochloride intravenously (IV) over 30 minutes once daily on days 1-5. Patients also receive, according to institutional standard, filgrastim subcutaneously (SC) beginning on day 6, 7, or 8 and continuing until hematopoietic recovery or pegfilgrastim SC on day 6, 7, or 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Tumor tissue samples may be collected periodically for translational studies.
After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.
- Conditions
- Cervical Adenocarcinoma, Cervical Adenosquamous Carcinoma, Cervical Small Cell Carcinoma, Cervical Squamous Cell Carcinoma, Recurrent Cervical Carcinoma, Stage III Cervical Cancer
- Being tested
- Filgrastim, Laboratory Biomarker Analysis, Pegfilgrastim, Topotecan Hydrochloride, Veliparib
- Medical subject headings
- Uterine Cervical Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FilgrastimBiological
Also called Filgrastim XM02, G-CSF, Neupogen, r-metHuG-CSF
Given SC
Laboratory Biomarker AnalysisOther
Correlative studies
PegfilgrastimBiological
Also called Filgrastim SD-01, filgrastim-SD/01, HSP-130, Neulasta
Given SC
Topotecan HydrochlorideDrug
Also called Hycamptamine, Hycamtin, SKF S-104864-A, Topotecan HCl
Given IV
VeliparibDrug
Also called ABT-888, PARP-1 inhibitor ABT-888
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment (veliparib, topotecan hydrochloride, filgrastim) | Experimental | Patients receive veliparib PO twice daily and topotecan hydrochloride IV over 30 minutes once daily on days 1-5. Patients also receive, according to institutional standard, filgrastim SC beginning on day 6, 7, or 8 and continuing until hematopoietic recovery or pegfilgrastim SC on day 6, 7, or 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Receives: Biological: Filgrastim; Other: Laboratory Biomarker Analysis; Biological: Pegfilgrastim; Drug: Topotecan Hydrochloride; Drug: Veliparib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tumor Response
Complete and Partial Tumor Response as Assessed by RECIST 1.1. Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1), Complete Response (CR), disappearance of all target and non-target lesions without evidence of new lesion; Partial Response (PR), at least 30% decrease in the sum of the longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD with no unequivocal progression of non-target lesions and no evidence of new lesion. Complete or partial response requires confirmation at greater than or equal to 4 weeks from initial documentation.
Measured: Every other cycle for first 6 months; then every 3 months thereafter until disease progression confirmed; and at any other time if clinically indicted based on symptoms or physical signs suggestive of progressive disease. The average time was 2.3 months
Number of Patients With Dose-limiting Toxicities (in Safety lead-in)
A dose-limiting toxicity (DLT) is assessed by NCI CTCAE v4, occurring during cycle 1 of therapy.: A dose-limiting toxicity (DLT) is defined as either hematologic or non-hematologic toxicity assessed by NCI CTCAE v4, occurring during cycle 1 of therapy, which cause any of the following: For hematologic toxicity - dose delay of greater than 2 weeks due to failure to recover counts, Treatment related febrile neutropenia, grade 4 neutropenia lasting >7 days, treatment related grade 4 thrombocytopenia or clinically significant bleeding with grade 3 thrombocytopenia. For non-hematologic toxicity; study treatment related grade 3 or 4 non-hematological toxicity (excluding anorexia, constipation, fatigue, hypersensitivity/allergic reaction to one of the study drugs, nausea \& vomiting, and grade 3 dehydration), grade 4 nausea and vomiting for >48 hours despite maximum medical management, electrolyte imbalance of > or equal to grade 3 that can be replaced within 48 hours; any drug related death
Measured: Up to 21 days
Adverse Events (Grade 3 or Higher) During Treatment Period
Number of participants with a maximum grade of 3 or higher during treatment period. Adverse events are graded and categorized using CTCAE v4.0.
Measured: During treatment period and up to 30 days after stopping the study treatment.The average of study treatment time was 2.3 months.
Secondary outcomes (3)
Progression-free Survival
Progression-free survival is the period of time from study entry to time of disease progression, death or date of last contact, whichever occurs first. Progression is defined as at least a 20% increase in the sum of the longest dimensions (LD) of target lesions taking as reference the smallest sum LD recorded since study entry, or unequivocal progression of existing non-target lesions, or the appearance of one or more new lesions, or global deterioration in health status attributable to the disease requiring a change in therapy without objective evidence of progression, or death due to disease without prior objective documentation of progression.
Measured: From study entry to disease progression, death or date of last contact, whichever occurs first, up to 5 years of follow-up.
Overall Survival
Overall survival is defined as the duration of time from study entry to time of death or the date of last contact.
Measured: From study entry to death or last contact, up to 5 years of follow-up.
Duration of Objective Response
Duration of objective response is defined as the duration from the time measurement criteria is met for partial or complete response by RECIST 1.1, whichever is first recorded, until the first date the recurrent or progressive disease is objectively documented. Per Response Evaluation Criteria in Solid Tumors (RECIST) criteria Complete Response (CR), disappearance of all target and non-target lesions without evidence of new lesion; Partial Response (PR), at least 30% decrease in the sum of the longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD with no unequivocal progression of non-target lesions and no evidence of new lesion. Complete or partial response requires confirmation at greater than or equal to 4 weeks from initial documentation.
Measured: Every other cycle for first 6 months; then every 3 months until disease progression confirmed; and at any other time if clinically indicated based on symptoms or signs suggestive of progressive disease.The average of study treatment time was 2.3 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2010 (estimated)
- Study startFeb 2011
- Primary completionJan 2016
- Study completionJan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Cervical AdenocarcinomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Collaborators
- NRG Oncology
- Responsible party
- Sponsor
- Investigators
- Charles Kunos, Principal investigator, NRG Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01266447
- Sponsor's protocol ID
- NCI-2011-02659
- Other IDs
- NCI-2011-02659, GOG-0127W, CDR0000691281, GOG-0127W, GOG-0127W, U10CA180868, U10CA027469
- Status last verified
- Aug 2019
- First submitted
- 23 Dec 2010
- Last updated
- 8 Aug 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 8 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Evaluation of ABT-888 (NCI Supplied Agent: ABT-888, NSC #737664), Topotecan (NSC # 609699) and Filgrastim or Pegfilgrastim in the Treatment of Persistent or Recurrent Squamous or Non-squamous Cell Carcinoma of the Cervix
- ClinicalTrials.gov ID
- NCT01266447
- Acronym / sponsor ID
- NCI-2011-02659
- Conditions
- Cervical Adenocarcinoma, Cervical Adenosquamous Carcinoma, Cervical Small Cell Carcinoma, Cervical Squamous Cell Carcinoma, Recurrent Cervical Carcinoma, Stage III Cervical Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Collaborators
- NRG Oncology
- Study start
- Feb 2011
- Primary completion
- Jan 2016 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 24 Dec 2010 (estimated)
- Results
- Posted 1 Feb 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II clinical trial is studying the how well veliparib, topotecan hydrochloride, and filgrastim or pegfilgrastim work in treating patients with persistent or recurrent cervical cancer. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as topotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by blocking them from dividing. Giving veliparib with chemotherapy may kill more tumor cells. Filgrastim or pegfilgrastim may cause the body to make more blood cells and help it recover from the side effects of chemotherapy.
Detailed description
PRIMARY OBJECTIVES:
- To estimate the antitumor activity (objective response rate by RECIST 1.1) of ABT-888 (veliparib) 10 mg administered orally twice a day on days 1 to 5 with topotecan (topotecan hydrochloride) 0.6 mg/m^2 administered IV once daily on days 1 to 5 of each cycle in patients with persistent or recurrent carcinoma of the cervix.
II. To determine the nature and degree of toxicity of ABT-888 and topotecan in patients with persistent or recurrent carcinoma of the cervix.
SECONDARY OBJECTIVES:
- To determine the duration of progression-free survival and overall survival.
TERTIARY OBJECTIVES:
- To determine whether evidence of an interaction exists between study treatments and tumor expression of poly(ADP-ribos)ylation of E2 protein, E6/E7 proteins, and p53R2 in relation to progression-free and overall survival or metastasis. (Translational) II. To explore the association between methylation of FanCF and BRCA in pre-treatment tumor samples and pre- and post-treatment biopsy samples and response, progression-free and overall survival of patients, and/or metastasis. (Translational)
OUTLINE:
Patients receive veliparib orally (PO) twice daily and topotecan hydrochloride intravenously (IV) over 30 minutes once daily on days 1-5. Patients also receive, according to institutional standard, filgrastim subcutaneously (SC) beginning on day 6, 7, or 8 and continuing until hematopoietic recovery or pegfilgrastim SC on day 6, 7, or 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Tumor tissue samples may be collected periodically for translational studies.
After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (veliparib, topotecan hydrochloride, filgrastim) | Experimental | Biological: Filgrastim, Other: Laboratory Biomarker Analysis, Biological: Pegfilgrastim, Drug: Topotecan Hydrochloride, Drug: VeliparibPatients receive veliparib PO twice daily and topotecan hydrochloride IV over 30 minutes once daily on days 1-5. Patients also receive, according to institutional standard, filgrastim SC beginning on day 6, 7, or 8 and continuing until hematopoietic recovery or pegfilgrastim SC on day 6, 7, or 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- 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
- 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 >= 10 mm when measured by computed tomography (CT), magnetic resonance imaging (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
- Patient must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST 1.1; 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
- Patients must not be eligible for a higher priority Gynecologic Oncology Group (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
- Patients must have a GOG performance status of 0, 1, or 2
Key exclusion criteria (6 listed)
- Patients are excluded who have had prior therapy with ABT-888 (veliparib), poly (ADP)-ribose polymerase inhibitors, or topotecan
- Patient with a history of other invasive malignancies, with the exception of non-melanoma skin cancer and other specific malignancies are excluded if there is any evidence of other malignancy being present within the last three years; patients are also excluded if their previous cancer treatment contraindicates this protocol therapy
- Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis OTHER THAN for the treatment of cervical cancer within the last three years are excluded; prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease
- Patients who have received prior chemotherapy for any abdominal or pelvic tumor OTHER THAN for the treatment of cervical cancer within the last three years are excluded; patients may have received prior adjuvant chemotherapy for cancer, provided that it was completed more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease
- Patients with seizures or history of seizures are ineligible
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FilgrastimAlso: Filgrastim XM02, G-CSF, Neupogen, r-metHuG-CSFGiven SC | Biological | Treatment (veliparib, topotecan hydrochloride, filgrastim) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (veliparib, topotecan hydrochloride, filgrastim) |
| PegfilgrastimAlso: Filgrastim SD-01, filgrastim-SD/01, HSP-130, NeulastaGiven SC | Biological | Treatment (veliparib, topotecan hydrochloride, filgrastim) |
| Topotecan HydrochlorideAlso: Hycamptamine, Hycamtin, SKF S-104864-A, Topotecan HClGiven IV | Drug | Treatment (veliparib, topotecan hydrochloride, filgrastim) |
| VeliparibAlso: ABT-888, PARP-1 inhibitor ABT-888Given PO | Drug | Treatment (veliparib, topotecan hydrochloride, filgrastim) |
Primary outcome
Tumor Response
Time frame: Every other cycle for first 6 months; then every 3 months thereafter until disease progression confirmed; and at any other time if clinically indicted based on symptoms or physical signs suggestive of progressive disease. The average time was 2.3 months
Complete and Partial Tumor Response as Assessed by RECIST 1.1. Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1), Complete Response (CR), disappearance of all target and non-target lesions without evidence of new lesion; Partial Response (PR), at least 30% decrease in the sum of the longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD with no unequivocal progression of non-target lesions and no evidence of new lesion. Complete or partial response requires confirmation at greater than or equal to 4 weeks from initial documentation.
Number of Patients With Dose-limiting Toxicities (in Safety lead-in)
Time frame: Up to 21 days
A dose-limiting toxicity (DLT) is assessed by NCI CTCAE v4, occurring during cycle 1 of therapy.: A dose-limiting toxicity (DLT) is defined as either hematologic or non-hematologic toxicity assessed by NCI CTCAE v4, occurring during cycle 1 of therapy, which cause any of the following: For hematologic toxicity - dose delay of greater than 2 weeks due to failure to recover counts, Treatment related febrile neutropenia, grade 4 neutropenia lasting >7 days, treatment related grade 4 thrombocytopenia or clinically significant bleeding with grade 3 thrombocytopenia. For non-hematologic toxicity; study treatment related grade 3 or 4 non-hematological toxicity (excluding anorexia, constipation, fatigue, hypersensitivity/allergic reaction to one of the study drugs, nausea \& vomiting, and grade 3 dehydration), grade 4 nausea and vomiting for >48 hours despite maximum medical management, electrolyte imbalance of > or equal to grade 3 that can be replaced within 48 hours; any drug related death
Adverse Events (Grade 3 or Higher) During Treatment Period
Time frame: During treatment period and up to 30 days after stopping the study treatment.The average of study treatment time was 2.3 months.
Number of participants with a maximum grade of 3 or higher during treatment period. Adverse events are graded and categorized using CTCAE v4.0.
3 secondary outcomes
Progression-free Survival
Time frame: From study entry to disease progression, death or date of last contact, whichever occurs first, up to 5 years of follow-up.
Overall Survival
Time frame: From study entry to death or last contact, up to 5 years of follow-up.
Duration of Objective Response
Time frame: Every other cycle for first 6 months; then every 3 months until disease progression confirmed; and at any other time if clinically indicated based on symptoms or signs suggestive of progressive disease.The average of study treatment time was 2.3 months.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Aug 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Charles Kunos principal investigator
NRG Oncology
78 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Filgrastim, Laboratory Biomarker Analysis and Pegfilgrastim in people with Cervical Adenocarcinoma and Cervical Adenosquamous Carcinoma, run by National Cancer Institute (NCI) at 78 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 26 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 78 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Feb 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Tumor Response (time frame: Every other cycle for first 6 months; then every 3 months thereafter until disease progression confirmed; and at any other time if clinically indicted based on symptoms or physical signs suggestive of progressive disease. The average time was 2.3 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Aug 2019.