Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Renal Insufficiency

Antineoplastic Agents

All Drugs and Chemicals

Hematinics

Paclitaxel

Carboplatin

Albumin-Bound Paclitaxel

Liver Extracts

Poly(ADP-ribose) Polymerase Inhibitors

Veliparib

Tubulin Modulators

Antimitotic Agents

Enzyme Inhibitors

ABT-888

Background:

- Paclitaxel and carboplatin are two standard drugs that stop cancer cells from reproducing. ABT-888 is an experimental cancer drug that may prevent cancer cells from "fixing" the damage done by chemotherapy drugs. This may make the chemotherapy work better. More tests are needed to determine the safety and effectiveness of ABT-888 plus chemotherapy. Researchers also want to find the best dose of ABT-888 for people who have kidney or liver problems in addition to cancer.

Objectives:

- To test the safety and effectiveness of ABT-888 plus carboplatin and paclitaxel in people who have both cancer and kidney or liver problems.

Eligibility:

* Individuals at least 18 years of age who have solid tumors that have not responded to standard treatment, and who also have kidney or liver problems.
* A small group of people with solid tumors and normal kidney and liver function may also receive treatment for study comparison purposes.

Design:

* Participants will be screened with a medical history and physical exam. They will have blood and urine tests, tumor samples, tests of liver and kidney function, and imaging studies. Participants will also provide a hair sample at the start of the study.
* Participants will take one dose of ABT-888 1 week before starting chemotherapy. The two chemotherapy drugs will be given on day 3 of a 21-day cycle. Participants will take ABT-888 daily for the first 7 days of each cycle.
* They will keep a diary to record medication doses and any side effects. They will also have frequent blood tests and imaging studies. Participants will provide more hair samples on day 3 of cycle 1 before and after having paclitaxel.
* Participants will continue treatment for up to 18 weeks as long as the cancer stops growing or shrinks and there are no serious side effects. Participants may have the option to continue treatment after the study is done.

Background:

The poly (ADP-ribose) polymerase (PARP) family of enzymes is critical for maintaining genomic stability by regulating a variety of DNA repair mechanisms. The carboplatin/paclitaxel combination has demonstrated a wide spectrum of clinical antitumor activity, making it an ideal platform for evaluation with novel agents, such as the PARP inhibitor ABT-888.

Objectives:

To determine the pharmacokinetics and pharmacodynamics of ABT-888 in patients with varying degrees of renal or hepatic dysfunction.

To determine the maximum tolerated dose (MTD) of ABT-888 in combination with carboplatin and paclitaxel for patients with varying degrees of liver or kidney dysfunction.

To provide dosing recommendations for ABT-888 in combination with carboplatin and paclitaxel based on degree of hepatic and renal impairment.

To define the dose-limiting toxicity and other toxicities associated with the use of this combination in patients with varying degrees of renal or hepatic dysfunction.

To evaluate the pharmacokinetic parameters of ABT-888, carboplatin and paclitaxel when administered as a combination in patients with varying degrees of renal or hepatic dysfunction.

To evaluate the pharmacodynamic measurement of PAR and platinum adducts in peripheral blood mononuclear cells (PBMC) and tumor cells associated with the use of this combination

in patients with varying degrees of renal or hepatic dysfunction.

Eligibility:

Patients must have histologically confirmed malignancy that is metastatic or unresectable, for which standard curative or palliative measures do not exist or are no longer effective, and for which there is expectation of response to the combination of carboplatin/paclitaxel (e.g., lung, ovarian, breast, and melanoma).

Patients must have adequate bone marrow function.

Patients with normal organ function, patients with all degrees of renal dysfunction, and patients with mild to severe hepatic dysfunction are allowed.

Study Design:

ABT-888 (80 mg) will be given orally on day -6 ( 1 day) of cycle 1 in all cohorts. ABT-888 in varying doses will then be given on days 1-7 of each cycle, with the dose depending on each patient's degree of renal or hepatic dysfunction.

Fixed doses of chemotherapy will be given intravenously on day 3 of each cycle. For patients with renal dysfunction, carboplatin will be given at AUC of 6 and paclitaxel at 175 mg/m2. For patients with hepatic dysfunction, carboplatin will be given at AUC of 6 and paclitaxel at doses adjusted to each patient's degree of hepatic dysfunction.

The dose of ABT-888 will be escalated to determine the MTD of the combination.

ABT-888, Carboplatin, and Paclitaxel for Cancer With Liver or Kidney Problems

An Early Phase 1 Study of ABT-888 in Combination With Carboplatin and Paclitaxel in Patients With Hepatic or Renal Dysfunction and Solid Tumors

National Cancer Institute (NCI)

Wounds and Injuries

Rare Diseases

Kidney Diseases

Acute Kidney Injury

Urologic Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Male Urogenital Diseases

Acute Graft Versus Host Disease

Adult patients undergoing major elective general abdominal surgery for ontological disease

Will be described: 1) the number of patients actually screened with postoperative serum creatinine and 2) the number of patients actually screened with the same parameter at the long-term after surgery

Serum creatinine

The perioperative approach adopted in a cohort of adult oncological patients undergoing major abdominal surgery will be described. In particular, the physician's attitude toward use of sCr for identification of patients at risk for PO-AKI will be described, as well as the patients who should be reassessed in the long term for progression toward CKD. The incidence and risk factors associated with PO-AKI and renal function deterioration within a year postoperatively will be also evaluated.

Perioperative Use of Serum Creatinine and Postoperative Acute Kidney Injury

Perioperative Use of Serum Creatinine and Postoperative Acute Kidney Injury: an Observational, Monocentric, Retrospective Study to Explore Physicians' Perception and Practice.

Number of actual patients screened postoperatively

Number of patients with a postoperative diagnostic increase of serum creatinine, in accordance with KDIGO guidelines

Number of actual patients screened at the long term

Number of patients with a long term reduction in GFR greater than 10 ml/min with respect to the baseline

Careggi Hospital

MD, clinical researcher

Diseases and Abnormalities at or Before Birth

Neoplasms

Polycystic Kidney Diseases

Polycystic Kidney, Autosomal Dominant

Kidney Neoplasms

Kidney Diseases, Cystic

Congenital Abnormalities

Abnormalities, Multiple

Ciliopathies

Genetic Diseases, Inborn

Urologic Neoplasms

Urogenital Neoplasms

Autosomal Dominant Multiple Pterygium Syndrome

sinistrin clearance measurements will be performed before and 90 min after oral protein load

sinistrin clearance dynamic measurement

Thomas F Mueller, Prof.

Andreja Figurek, Dr. med.

The number of people with kidney disease is constantly rising and renal failure represents one of the major health care burdens globally. An accurate measurement of kidney function is urgently needed to better understand and treat loss of renal function. Kidneys have an intrinsic reserve capacity to respond to a higher work load by increasing filtration in their nephrons. The number of nephrons and their reserve capacity define how well kidneys can adapt to an increased demand and disease.

The degree of renal reserve capacity becomes particularly important when the number of functioning nephrons is significantly reduced either due to surgical removal of one kidney as in living kidney donation or in tumor nephrectomy or due to progressive injury as in autosomal dominant polycystic kidney disease (ADPKD). A reduced functional reserve likely reflects an impaired adaptive capacity and increased risk of accelerated loss of function in the remaining single kidney or in kidneys exposed to a disease. Despite the importance of accurately measuring baseline and reserve capacity renal function, due to the time- and laborintensive procedure, in clinical routine this testing is rarely done.

Investigators aim to measure renal functional reserve (RFR) and loss of function in patients undergoing nephrectomy (living kidney donors and renal tumor patients) as well as in patients with ADPKD.

The results should provide evidence whether renal functional reserve indeed predicts adaptive capacity and functional loss after removal of a healthy kidney (living donors), of a tumor kidney (cancer patients) or in progressive kidney disorders (ADPKD patients).

Investigators are confident that the proposed project will enhance the understanding of progressive kidney disease and with this improve donor safety, planning of tumor nephrectomy, and prediction of renal functional loss as well as provide a strong argument that dynamic renal function testing, i.e. accurate measurement of baseline and reserve capacity, is necessary in certain disease entities.

The measurement of RFR will be performed by dynamic testing of the changes in baseline glomerular filtration rate (GFR) induced by an oral protein load. Sinistrin (a polyfructosan with identical clearance characteristics to inulin) will be used to measure GFR.

Dynamic Measurement of Renal Functional Reserve as a Predictor of Long-Term Renal Function

Sinistrin levels in plasma before and after oral protein load. Participants with impaired RFR are expected to have higher sinitrin levels in plasma.

Thomas Mueller

Prof. Dr.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
ABT-888, Carboplatin, and Paclitaxel for Cancer With Liver or Kidney Problems	NCT01419548	Neoplasms	ABT-888 Carboplatin Paclitaxel	18 Years - 110 Years	National Institutes of Health Clinical Center (CC)
ABT-888, Carboplatin, and Paclitaxel for Cancer With Liver or Kidney Problems	NCT01419548	Neoplasms	ABT-888 Carboplatin Paclitaxel	18 Years - 110 Years	National Institutes of Health Clinical Center (CC)
Perioperative Use of Serum Creatinine and Postoperative Acute Kidney Injury	NCT04341974	Surgery Malignancy Acute Kidney In... Cronich Kidney ...	Serum creatinin...	18 Years -	Careggi Hospital
Dynamic Measurement of Renal Functional Reserve as a Predictor of Long-Term Renal Function	NCT03442647	Adult Polycysti... Kidney Neoplasm... Kidney Dysfunct...	sinistrin clear...	18 Years -	University of Zurich

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