Questions About Cancer? 1-800-4-CANCER

Featured Clinical Trials

Cancer Studies Highlighted in the NCI Cancer Bulletin
  • Posted: 01/12/2010

PARP Inhibitor and Metronomic Chemotherapy for Refractory Cancer

Name of the Trial

Phase I Study of ABT-888 and Metronomic Cyclophosphamide in Patients with Refractory Solid Tumors or Lymphoma (NCI-09-C-0048). See the protocol summary 1.

Principal Investigator

Dr. Shivaani Kummar
Dr. Shivaani Kummar
Principal Investigator

Dr. Shivaani Kummar, NCI Center for Cancer Research

Why This Trial Is Important

Many chemotherapy drugs kill cancer cells by causing damage to DNA. However, cells can employ a number of mechanisms to repair this damage. When cells experience drug-induced breaks in their DNA strands, proteins called PARPs bind to the DNA at the sites of the breaks and recruit other proteins involved in DNA repair. This process can allow cancer cells to continue to survive and grow despite the damage caused by chemotherapy treatment.

The oral drug ABT-888 blocks the activity of PARP proteins, thereby interfering with the ability of cancer cells to repair their DNA. Combining ABT-888 with a chemotherapy drug that causes DNA strand breaks, such as cyclophosphamide 2, may result in a greater antitumor effect.

In this clinical trial, patients with solid tumors or lymphomas that have not responded to previous treatment (refractory cancer), or for which no effective treatment exists, will receive ABT-888 and metronomic cyclophosphamide. The term metronomic refers to the administration of drugs at lower than normal doses more frequently than usual. Metronomic chemotherapy may work differently from treatment with the same drugs at higher doses. Metronomic cyclophosphamide still causes DNA damage, but also exhibits an antiangiogenic effect, is less toxic, and can be given in pill form daily, making it more convenient for patients than intravenous cyclophosphamide.

Doctors will assess the safety, tolerability, and pharmacokinetics of this combination, as well as establish the maximum tolerated dose of ABT-888 and examine the effects of treatment on molecular markers in blood and tumor samples.

"Our goal with this study is to come up with a regimen that is not only effective but also well tolerated and orally available," said Dr. Kummar.

For More Information

See the lists of eligibility criteria 3 and trial contact information 4 or call the NCI Clinical Trials Referral Office at 1-888-NCI-1937. The call is toll free and confidential.

Related Pages



Glossary Terms

ABT-888
A substance being studied in the treatment of breast cancers caused by mutations (changes) in the BRCA1 and BRCA2 genes. It is also being studied in the treatment of other types of cancer. It blocks an enzyme involved in many functions of the cell, including the repair of DNA damage. DNA damage may be caused by normal cell actions, UV light, some anticancer drugs, and radiation used to treat cancer. ABT-888 may cause cancer cells to die. It is a type of poly(ADP-ribose) polymerase inhibitor. Also called PARP-1 inhibitor ABT-888 and veliparib.
antiangiogenic (AN-tee-AN-jee-oh-JEH-nik)
Having to do with reducing the growth of new blood vessels.
DNA
The molecules inside cells that carry genetic information and pass it from one generation to the next. Also called deoxyribonucleic acid.
lymphoma (lim-FOH-muh)
Cancer that begins in cells of the immune system. There are two basic categories of lymphomas. One kind is Hodgkin lymphoma, which is marked by the presence of a type of cell called the Reed-Sternberg cell. The other category is non-Hodgkin lymphomas, which includes a large, diverse group of cancers of immune system cells. Non-Hodgkin lymphomas can be further divided into cancers that have an indolent (slow-growing) course and those that have an aggressive (fast-growing) course. These subtypes behave and respond to treatment differently. Both Hodgkin and non-Hodgkin lymphomas can occur in children and adults, and prognosis and treatment depend on the stage and the type of cancer.
maximum tolerated dose (MAK-sih-mum TAH-leh-RAY-ted …)
The highest dose of a drug or treatment that does not cause unacceptable side effects. The maximum tolerated dose is determined in clinical trials by testing increasing doses on different groups of people until the highest dose with acceptable side effects is found. Also called MTD.
metronomic therapy (MEH-truh-NAH-mik THAYR-uh-pee)
Continuous or frequent treatment with low doses of anticancer drugs, often given with other methods of therapy.
molecular marker (muh-LEH-kyoo-ler MAR-ker)
A biological molecule found in blood, other body fluids, or tissues that is a sign of a normal or abnormal process, or of a condition or disease. A molecular marker may be used to see how well the body responds to a treatment for a disease or condition. Also called biomarker and signature molecule.
PARP
A type of enzyme involved in many functions of the cell, including the repair of DNA damage. DNA damage may be caused by normal cell actions, UV light, some anticancer drugs, and radiation used to treat cancer. Inhibitors of one enzyme, PARP-1, are being studied in the treatment of cancer. Also called poly (ADP-ribose) polymerase.
pharmacokinetics (FAR-muh-koh-kih-NEH-tix)
The activity of drugs in the body over a period of time, including the processes by which drugs are absorbed, distributed in the body, localized in the tissues, and excreted.
protein (PROH-teen)
A molecule made up of amino acids that are needed for the body to function properly. Proteins are the basis of body structures such as skin and hair and of substances such as enzymes, cytokines, and antibodies.
refractory cancer (reh-FRAK-tor-ee KAN-ser)
Cancer that does not respond to treatment. The cancer may be resistant at the beginning of treatment or it may become resistant during treatment. Also called resistant cancer.
solid tumor (SAH-lid TOO-mer)
An abnormal mass of tissue that usually does not contain cysts or liquid areas. Solid tumors may be benign (not cancer), or malignant (cancer). Different types of solid tumors are named for the type of cells that form them. Examples of solid tumors are sarcomas, carcinomas, and lymphomas. Leukemias (cancers of the blood) generally do not form solid tumors.

Table of Links

1http://www.cancer.gov/clinicaltrials/NCI-09-C-0048
2http://www.cancer.gov/cancertopics/druginfo/cyclophosphamide
3http://www.cancer.gov/clinicaltrials/NCI-09-C-0048#EntryCriteria_CDR0000629899
4http://www.cancer.gov/clinicaltrials/NCI-09-C-0048#ContactInfo_CDR0000629899
5http://www.cancer.gov/clinicaltrials/search