Veliparib and Radiation Therapy in Treating Patients With Advanced Solid Malignancies With Peritoneal Carcinomatosis, Epithelial Ovarian, Fallopian, or Primary Peritoneal Cancer

NCT01264432 | Completed Phase 1

• 11 other identifiers: NCI-2012-02913NA_00043143J1097NA_00043143, J1097CDR00006918818813P30CA006973U01CA132123U01CA070095UM1CA186644UM1CA186691
• Study Type: interventional
• Target: 34
• Locations: 2 countries
• Sites: 3

Brief Summary

This phase I trial studies the side effects and best dose of veliparib when given together with radiation therapy in treating patients with advanced solid malignancies (abnormal cells divide without control and can invade nearby tissues) with peritoneal carcinomatosis, epithelial ovarian, fallopian, or primary peritoneal cancer. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy x rays to kill tumor cells. Giving veliparib with radiation therapy may kill more tumor cells.

Conditions

Adult Solid Neoplasm; Peritoneal Carcinomatosis; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma

Outcome Measures

Primary Outcomes (1)

• Maximum tolerable dose defined as the highest dose at which 0 or 1 dose-limiting toxicities are observed in six patients as graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

  Reported with exact binomial proportions and 95% confidence intervals.

  28 days

Secondary Outcomes (5)

• Changes in quality of life, assessed using the QLQC-30 standardized questionnaire

  From baseline to 4 years

• Clinical activity assessed by response (complete, partial, and overall), measured by RECIST 1.1 criteria

  Up to 4 years

• Microsatellite instability (MSI)

  Baseline

• Presence of DNA repair proteins

  Baseline

• Proportion of toxicities of the combination of veliparib and LDRWAR as graded by the NCI CTCAE version 4.0

  Up to 4 weeks after completion of study treatment

Study Arms (1)

Treatment (veliparib, LDRWAR)

EXPERIMENTAL

Patients receive veliparib PO BID on days 1-21 (days 5-21 of course 1). Patients undergo LDFWAR in BID on days 1 and 5 of weeks 1-3. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment; Radiation: Radiation Therapy; Drug: Veliparib

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (veliparib, LDRWAR)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (veliparib, LDRWAR)

Radiation Therapy RADIATION

Undergo LDFWAR

Also known as: Cancer Radiotherapy, Irradiate, Irradiated, irradiation, Radiation, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Treatment (veliparib, LDRWAR)

Veliparib DRUG

Given PO

Also known as: ABT-888, PARP-1 inhibitor ABT-888

Treatment (veliparib, LDRWAR)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Dose levels 1-4 must have histologically proven solid malignancy that is metastatic or unresectable with metastatic peritoneal carcinomatosis; as this entity may be difficult to image, peritoneal disease can be documented through other modalities such as operative notes, clinical notes/symptoms, etc as well as imaging
• Dose levels 5 and 6 will be open only to patients with recurrent or persistent primary epithelial ovarian, fallopian or peritoneal cancers; at these dose levels, measurable disease in the abdominal cavity must be present but peritoneal carcinomatosis is not required for eligibility
• Patients must have failed first line standard therapy or have no acceptable standard treatment options; for patients on dose levels 5 and 6, patients may be platinum sensitive, platinum resistant or platinum refractory
• Ability to understand and the willingness to sign a written informed consent document
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 1
• Life expectancy of greater than 3 months
• Absolute neutrophil count (ANC) \>= 1,500/mcL
• Platelets \>= 100,000/mcL
• Total bilirubin =\< 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x ULN
• Creatinine =\< 1.5 x ULN OR creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal
• Calcium within normal limit (WNL)
• No surgery, hormonal therapy or chemotherapy within four weeks; for dose levels 5 and 6, patients receiving mitomycin C or nitrosoureas must discontinue treatment 6 weeks prior to registration and any hormonal treatment directed at the malignant tumor must be discontinued at least one week prior to registration; continuation of hormone replacement therapy is permitted
• No previous abdominal radiation; if the patient has received previous pelvic radiation there should not be any overlap between the current and previous radiation fields
• Toxicities of prior chemotherapy recovered to grade 1 or less except for stable grade 2 peripheral neuropathy

You may not qualify if:

• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• Patients who are currently receiving any other investigational agents
• Brain metastases: patients with treated and stable brain metastasis for 3 months, off steroids will be eligible
• Patients who demonstrate any clinical evidence of bleeding
• Patients who have demonstrated an inability to swallow oral medications
• Patients who currently have an active gastrointestinal obstruction, have had a gastrointestinal obstruction within the last 30 days prior to enrollment and/or are actively requiring parenteral nutrition are excluded; patients who have had a history of any prior gastrointestinal obstruction requiring surgical intervention are also excluded
• Patients who have a known hypersensitivity to the components of the study drug, its analogs or drugs of a similar chemical or biologic composition
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with veliparib
• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
• Patients who have uncontrolled ascites
• Patients with active seizures or a history of seizure are not eligible
• Patients previously treated with poly (ADP-ribose) polymerase 1 (PARP) inhibitors

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (3)

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

University Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

MeSH Terms

Conditions

Peritoneal Neoplasms; Fallopian Tube Neoplasms; Ovarian Neoplasms

Interventions

Radiotherapy; Radiation; veliparib

Condition Hierarchy (Ancestors)

Abdominal Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Peritoneal Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Fallopian Tube Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Therapeutics; Physical Phenomena

Study Officials

• Nilofer Azad

  Johns Hopkins University/Sidney Kimmel Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2010
• First Posted: December 21, 2010
• Study Start: January 1, 2011
• Primary Completion: November 15, 2016
• Study Completion: November 15, 2016
• Last Updated: November 21, 2017

Record last verified: 2017-11

Locations

US (2); CA (1)