Neoplasms

All Conditions

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Adenocarcinoma

Pancreatic Neoplasms

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Pancreatic Cancer

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Gastrointestinal Agents

Hematinics

Vitamins

Gemcitabine

Capecitabine

Paclitaxel

Irinotecan

Leucovorin

Fluorouracil

Albumin-Bound Paclitaxel

Cisplatin

Oxaliplatin

Folfirinox

Pancrelipase

Pancreatin

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Topoisomerase I Inhibitors

Enzyme Inhibitors

Antidotes

Protective Agents

Folic Acid

Vitamin B Complex

Trace Elements

Folate

Vitamin B9

Milestone 1: Targeted chemotherapy prior to surgery: 8 weeks targeted chemotherapy; restaging.

Milestone 2: Before surgery: Chemoradiotherapy (cRXT); restaging Milestone 3: Before surgery: 8 weeks targeted chemotherapy; restaging; chemoradiotherapy (cXRT); restaging.

Milestone 4: standard FOLFIRINOX chemotherapy prior to surgery: 8 weeks FOLFIRINOX (standard chemotherapy); restaging; standard chemoradiotherapy (cXRT); restaging.

Milestone 5: After surgery: 8 weeks targeted chemotherapy; restaging; chemoradiotherapy (cXRT); restaging.

Milestone 6: Gemcitabine after surgery: 8 weeks standard Gemcitabine (chemotherapy); restaging; chemoradiotherapy (cXRT); restaging.

Milestone 7: After surgery: chemoradiotherapy (cXRT); restaging. Milestone 8: Gemcitabine after surgery: 8 weeks Gemcitabine (chemotherapy); restaging; 8 weeks Gemcitabine (chemotherapy); restaging.

Milestone 9: No additional therapy after surgery. Milestone 10: After surgery no additional treatment.

The molecular profile from the biopsy before surgery will point to a particular chemotherapy treatment.

Milestone 1: Targeted chemotherapy prior to surgery

A radio-sensitizing chemotherapy agent (either Gemcitabine or Capecitabine) will be given. Using 3D conformal or intensity-modulated radiation therapy (IMRT) techniques, patients will receive a total dose of 50.4 Gy prescribed to the 95% isodose at 1.8 Gy/fraction (28 fractions).

Milestone 2: Chemoradiotherapy (cXRT)

Milestone 3: Targeted chemotherapy prior to surgery

A radio-sensitizing chemotherapy agent (either Gemcitabine or Capecitabine) will be given. Using 3D conformal or IMRT techniques, patients will receive a total dose of 50.4 Gy prescribed to the 95% isodose at 1.8 Gy/fraction (28 fractions).

Milestone 3: Chemoradiotherapy (cXRT)

A biopsy of the borderline tumor does not provide a molecular profile that can be used to target treatment. The treatment will be standard FOLFIRINOX chemotherapy regimen.

Milestone 4: standard FOLFIRINOX chemotherapy prior to surgery

Milestone 4: Chemoradiotherapy (cXRT)

The molecular profile from the surgical specimen will point to a particular chemotherapy treatment.

Milestone 5: Targeted chemotherapy after surgery

Milestone 5: Chemoradiotherapy (cXRT)

Milestone 6: Gemcitabine after surgery

Milestone 6: Chemoradiotherapy (cXRT)

Milestone 7: Chemoradiotherapy (cXRT)

Milestone 8: Targeted chemotherapy after surgery

Milestone 9: Gemcitabine after surgery

The molecular profile of the tumor that was removed during surgery points to a lack of treatment affect for available therapies. No additional therapy is recommended.

Milestone 10: No additional therapy after surgery

Douglas B. Evans, M.D., FACS

Kathleen Christians, M.D., FACS

Susan Tsai, M.D., M.H.S.

Paul Ritch, M.D.

In this clinical trial, if the doctor knows or suspects that a growth in the pancreas is cancer (adenocarcinoma), then a sample of the growth is tested (the test is called molecular profiling). The results of the test are used by the doctor to recommend therapy (chemotherapy and radiation therapy) that the patient will receive before having surgery to remove the adenocarcinoma. When the patient goes to surgery, the adenocarcinoma that is removed is tested again. The results of that test are used to guide the choice of therapy after surgery.

The chemotherapy drugs and the radiation therapy used in this clinical trial are already approved for treatment of pancreas cancer. This trial is intended to establish which treatment is best for a specific patient, based on test results from that patient's actual adenocarcinoma. In the past, the decision as to which treatment the patient will receive was not based on testing of the actual adenocarcinoma.

See treatment pathways at http://www.mcw.edu/surgery/patientinfo/Pancreatic-Cancer-Trial.htm.

Hypothesis: Resectability rate, overall survival rate and progression-free survival in subjects with adenocarcinoma of the pancreas will be superior for who receive targeted "personalized" therapy.

Pancreas Cancer: Molecular Profiling as a Guide to Therapy Before and After Surgery ("Personalized Medicine")

A Prospective Phase II Trial of Molecular Profiling to Guide Neoadjuvant Therapy for Resectable and Borderline Resectable Adenocarcinoma of the Pancreas

This outcome measure is the number of subjects completing therapy up to and including surgical resection. In this context, surgical excision of residual tumor is an option in the progression of usual care. Surgery was contraindicated for some participants. This measure is the number of subject who were eligible for and completed the surgical procedure.

This measure is the median time of survival (in months) at five years from the initiation of therapy. Results will be presented for two cohorts: subjects completing neoadjuvant therapy and surgical resection; and subjects completing neoadjuvant therapy but without surgical resection.

This measure is the number of subjects not experiencing tumor progression at five years from initiating therapy.

The number of subjects for whom a biomarker (i.e., molecular profile) was used to determine the course of treatment.

The number of tumors showing a histologic response. Histological response will be measured using the Ryan Score method as defined by the American Joint Committee on Cancer, 7th edition (see Edge, 2010). Grading categories are defined as: Grade 0 (complete response); Grade 1 (near complete response); Grade 2 (partial response); and Grade 3 (poor or no response).

University of Cincinnati

Medical College of Wisconsin

Professor

The treatment milestones are represent the usual care for this condition. Only serious adverse events were collected.

Milestones Related to Therapy

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Susan Tsai, MD

Milestones Related to Usual Therapy

Number of Subjects Completing Therapy Including Surgical Resection.

This population includes the participants who were eligible for and completed surgical resection of residual tumor. Milestone 1: Targeted chemotherapy prior to surgery: 8 weeks targeted chemotherapy; restaging.

Milestone 2: Before surgery: Chemoradiotherapy (cRXT); restaging Milestone 3: Before surgery: 8 weeks targeted chemotherapy; restaging; chemoradiotherapy (cXRT); restaging.

Milestone 4: standard FOLFIRINOX chemotherapy prior to surgery: 8 weeks FOLFIRINOX (standard chemotherapy); restaging; standard chemoradiotherapy (cXRT); restaging.

Milestone 5: After surgery: 8 weeks targeted chemotherapy; restaging; chemoradiotherapy (cXRT); restaging.

Milestone 6: Gemcitabine after surgery: 8 weeks standard Gemcitabine (chemotherapy); restaging; chemoradiotherapy (cXRT); restaging.

Milestone 7: After surgery: chemoradiotherapy (cXRT); restaging. Milestone 8: Gemcitabine after surgery: 8 weeks Gemcitabine (chemotherapy); restaging; 8 weeks Gemcitabine (chemotherapy); restaging.

Milestone 9: No additional therapy after surgery. Milestone 10: After surgery no additional treatment.

Milestones Related to Therapy (Resected)

This population includes participants for whom surgical resection was contraindicated and did not occur.

Milestone 1: Targeted chemotherapy prior to surgery: 8 weeks targeted chemotherapy; restaging.

Milestone 2: Before surgery: Chemoradiotherapy (cRXT); restaging Milestone 3: Before surgery: 8 weeks targeted chemotherapy; restaging; chemoradiotherapy (cXRT); restaging.

Milestone 4: standard FOLFIRINOX chemotherapy prior to surgery: 8 weeks FOLFIRINOX (standard chemotherapy); restaging; standard chemoradiotherapy (cXRT); restaging.

Milestones Related to Therapy (Non-Resected)

Results will be presented for two cohorts: subjects completing neoadjuvant therapy and surgical resection; and subjects completing neoadjuvant therapy but without surgical resection.

Overall Survival in Months

Progression-free Survival

Use of Biomarkers to Determine Course of Treatment

Pathology results were not reported for two subject.

Histologic Response to Targeted Chemotherapeutic Regimens in Resected Tumors.

The milestones described below represent the treatment progression patients follow for treatment of this disease. The milestone represents changes in therapy based on medical condition and are not intended to represent discrete events in the investigation. Study are not parsed for analysis among the treatment milestones.

Milestone 1: Targeted chemotherapy prior to surgery: 8 weeks targeted chemotherapy; restaging.

Milestone 2: Before surgery: Chemoradiotherapy (cRXT); restaging Milestone 3: Before surgery: 8 weeks targeted chemotherapy; restaging; chemoradiotherapy (cXRT); restaging.

Milestone 4: standard FOLFIRINOX chemotherapy prior to surgery: 8 weeks FOLFIRINOX (standard chemotherapy); restaging; standard chemoradiotherapy (cXRT); restaging.

Milestone 5: After surgery: 8 weeks targeted chemotherapy; restaging; chemoradiotherapy (cXRT); restaging.

Milestone 6: Gemcitabine after surgery: 8 weeks standard Gemcitabine (chemotherapy); restaging; chemoradiotherapy (cXRT); restaging.

Milestone 7: After surgery: chemoradiotherapy (cXRT); restaging. Milestone 8: Gemcitabine after surgery: 8 weeks Gemcitabine (chemotherapy); restaging; 8 weeks Gemcitabine (chemotherapy); restaging.

Milestone 9: No additional therapy after surgery. Milestone 10: After surgery no additional treatment.

Milestones Related to Standard Therapy

Overall Study

Respiratory Tract (Lung and Bronchial) Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Lung Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Uterine Cervical Neoplasms

Carcinoma, Renal Cell

Kidney Neoplasms

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Endocrine System Diseases

Gonadal Disorders

Urologic Neoplasms

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Renal Cell Carcinoma

Anti-Infective Agents

Docetaxel

Technetium Tc 99m Sestamibi

polysaccharide-K

Radiopharmaceuticals

Patients receive 40 mg/m\^2 docetaxel intravenous (IV) over 1 hour on days 1 and 8 and 150 mg tariquidar intravenous (IV) over 30 minutes on days 8 and 22. From cycle 2 and onward 75 mg/m\^2 docetaxel was administered every 21 days in combination with a single 150 mg dose.

Patients receive docetaxel intravenous (IV) over 1 hour on days 1 and 8 and tariquidar intravenous (IV) over 30 minutes on days 1 and 22.

Patients receive docetaxel intravenous (IV) over 1 hour on days 1 and 8.

docetaxel

Patients receive tariquidar intravenous (IV) over 30 minutes on days 8 and 22.

tariquidar

Bolus injection of 29 mCi of 99mTc-sestamibi intravenously for each imaging study.

99mTc-sestamibi imaging

Susan E Bates, M.D.

The purpose of this study is three-fold: 1) to examine the ability of the experimental drug tariquidar to improve chemotherapy results by blocking a protein (P-glycoprotein) on some cancer cells that acts to pump out cancer drugs; 2) examine how tariquidar interacts with the cancer drug docetaxel; and 3) evaluate the effectiveness of combination treatment with tariquidar and docetaxel in treating patients with lung, ovarian, or cervical cancer.

Patients 18 years of age and older with recurrent or metastatic (spreading) lung, cervical, or ovarian cancer who cannot benefit from any standard treatment may be eligible for this study. Candidates will be screened with a medical history and physical examination; review of pathology slides; blood and urine tests; imaging tests, including computed tomography (CT) or magnetic resonance imaging (MRI) scans; chest x-ray, electrocardiogram (EKG); and possibly echocardiogram.

Participants will undergo the following tests and procedures:

Blood draw. Blood is drawn before treatment begins to establish baseline levels for future blood tests. Blood counts are done twice weekly after chemotherapy begins.

Central venous catheter placement. A plastic tube is put into a major vein in the chest. It is used to give the study drugs or other medications, including antibiotics and blood transfusions, if needed, and to withdraw blood samples. The line is usually placed under local anesthesia in the radiology department or the operating room. It can stay in the body for months or be removed after each treatment is completed.

Chemotherapy. Treatment cycles are 21 days. Both drugs are given on day 1 of each cycle. First, tariquidar is given as a 30-minute infusion. One hour after the tariquidar infusion, docetaxel is infused over 1 hour. (For the first cycle only, docetaxel is given in divided doses one week apart and tariquidar is administered on either day 1 or day 8. The order of tariquidar administration is randomized to generate optimal pharmacokinetic data. Patients will be hospitalized for several days during this cycle to gather research data). The tariquidar dose remains the same throughout the study. Docetaxel may be increased or decreased from cycle to cycle, based on side effects.

Intrinsic and acquired drug resistance remain major obstacles in the treatment of cancer. Accumulating evidence indicates that in some malignancies P-glycoprotein (Pgp) can confer resistance, and that its reversal can improve therapeutic outcome. Clinical trials investigating Pgp antagonists have been hampered by the occurrence of unpredictable pharmacokinetic interactions, which have required dose reductions of the chemotherapeutic agents to avert excessive toxicity. Tariquidar (XR9576) is a new Pgp antagonist that is more potent and has prolonged activity. Phase I trials with paclitaxel, vinorelbine, and docetaxel have demonstrated that tariquidar (XR9576) has minimal pharmacokinetic interactions while surrogate studies have confirmed in vivo inhibition of Pgp-mediated drug transport.This study seeks to determine the pharmacokinetic interaction, if any between docetaxel and tariquidar and to evaluate the potential for activity in lung, ovarian, primary peritoneal, fallopian tube and cervical cancers. Renal cell cancer has been added in a 3/1/06 amendment. The secondary goal is to evaluate the impact of tariquidar on uptake of (99m)Tc-sestamibi in recurrent or metastatic tumors of patients with lung, ovarian, renal or cervical cancer.

Tariquidar and Docetaxel to Treat Patients With Lung, Ovarian, Renal and Cervical Cancer

A Clinical Trial of the P-Glycoprotein Antagonist, Tariquidar (XR9576), in Combination With Docetaxel in Patients With Lung, Ovarian, Renal and Cervical Cancer: Analysis of the Interaction Between Tariquidar and Docetaxel

In the first cycle patients were to receive docetaxel on days 1 and 8 and to be randomized to receive tariquidar on either day 1 or 8. Thus pharmacokinetic data with and without tariquidar can be compared.

Here are the total number of participants with adverse events. For the detailed list of adverse events see the adverse event module.

Response is determined by RECIST criteria defined as changes in only the largest diameter (unidimensional measurement) of the tumor lesion. Lesions are either measurable or non-measurable. Measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>/- 20 mm with conventional techniques (CT, MRI, xray) or as \>/- 10 mm with a spiral CT scan. Non-measurable lesions are defined as all other lesions (or sites of disease) including small lesions (longest diameter \<20 mm with conventional techniques or \<10 mm using spiral CT.

A significant change in the area under the curve(AUC) in liver tissue (normal tissue as a surrogate) is defined as P\<0.001. A secondary objective of this study was to establish whether tariquidar (150 mg) modulates Pgp in liver. Sestamibi is a Pgp substrate that may be a surrogate for measuring drug efflux from tumors. A baseline Tc-sestamibi scan was obtained before the administration of tariquidar. A minimum of 48 hours later, on or about day 22 a single dose of tariquidar was administered, followed by a second Tc-sestamibi scan.

99mTc-sestamibi is a radionuclide imaging agent used to study cardiac function that has also been shown to be a substrate for P-glycoprotein- mediated drug efflux. Because of the high expression of Pgp in liver tissue, sestamibi uptake in liver tissue is often monitored as a marker of Pgp inhibition. A significant change in the area under the curve(AUC) in liver tissue (normal tissue as a surrogate) is defined as P\<0.001.

National Cancer Institute (NCI)

Susan E. Bates

Patients on Docetaxel on Days 1, 8 & Tariquidar on Day 8, 22

Patients on Docetaxel on Days 1, 8 & Tariquidar on Days 1, 22

Patients receive 40 mg/m\^2 docetaxel intravenous (IV) over 1 hour on days 1 and 8 and 150 mg tariquidar intravenous (IV) over 30 minutes on days 8 and 22. From cycle 2 and onward 75 mg/m\^2 docetaxel was administered every 21 days in combination with a single 150 mg tariquidar dose.

Pts Who Received Docetaxel on Day 1, 8, & Tariquidar Day 8,22

Patients receive docetaxel intravenous (IV) over 1 hour on days 1 and 8 and tariquidar intravenous (IV) over 30 minutes on days 1 and 22.From cycle 2 and onward 75 mg/m\^2 docetaxel was administered every 21 days in combination with a single 150 mg tariquidar dose.

Pts Who Received Docetaxel on Days 1, 8, & Tariquidar Day 1,22

Total

Age Continuous

Susan E. Bates, M.D.

C1D1

C1D8

Both Groups (C1D1 + C1D8)

40 mg/m\^2 docetaxel over 1 hour on days 1 and 8.

Docetaxel Alone

40 mg/m\^2 docetaxel intravenous (IV) over 1 hour on days 1 and 8 and 150 mg tariquidar intravenous (IV) over 30 minutes on either day 1 or 8 and then again on day 22. From cycle 2 and onward 75 mg/m\^2 docetaxel was administered every 21 days in combination with a single 150 mg dose of tariquidar.

With Tariquidar

Docetaxel alone (C1D1 = 21 patients; C1D8 = 18 patients) Docetaxel with Tariquidar (C1D1 = 21 patients; C1D8 = 16 patients) Data were evaluable in 39 patients. Paired data from 31 participants were evaluable.

Geometric Mean of Maximum Concentration of the Drug (Cmax)

The Number of Participants With Adverse Events.

Docetaxel alone (C1D1 = 21 patients; C1D8 = 18 patients) Docetaxel with Tariquidar (C1D1 = 21 patients; C1D8 = 16 patients) Pharmacokinetic data were evaluable in 39 patients. Paired data from 31 participants were evaluable.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pancreas Cancer: Molecular Profiling as a Guide to Therapy Before and After Surgery ("Personalized Medicine")	NCT01726582	Pancreatic Aden...	Milestone 1: Ta... Milestone 2: Ch... Milestone 3: Ta... Milestone 3: Ch... Milestone 4: st... Milestone 4: Ch... Milestone 5: Ta... Milestone 5: Ch... Milestone 6: Ge... Milestone 6: Ch... Milestone 7: Ch... Milestone 8: Ta... Milestone 9: Ge... Milestone 10: N...	18 Years -	Medical College of Wisconsin
Tariquidar and Docetaxel to Treat Patients With Lung, Ovarian, Renal and Cervical Cancer	NCT00069160	Lung Neoplasms Ovarian Neoplas... Cervix Neoplasm... Renal Neoplasms	docetaxel tariquidar 99mTc-sestamibi...	18 Years -	National Institutes of Health Clinical Center (CC)
Surgery Plus Chemotherapy (Doxorubicin, Vincristine and Etoposide), Mitotane, and Tariquidar to Treat Adrenocortical Cancer	NCT00071058	Adrenal Cortex ...	XR9576 (Tariqui...	18 Years -	National Institutes of Health Clinical Center (CC)
Prospective Collection of Tumor Biopsy and Plasma Samples From Cancer Patients Treated With Molecular Targeted Therapies or Immunotherapy	NCT03835520	Cancer	Immunotherapeut... Molecular Targe...	18 Years -	Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Surgery Plus Chemotherapy (Doxorubicin, Vincristine and Etoposide), Mitotane, and Tariquidar to Treat Adrenocortical Cancer	NCT00071058	Adrenal Cortex ...	XR9576 (Tariqui...	18 Years -	National Institutes of Health Clinical Center (CC)

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