1B-12-6 Light-Scattering Spectroscopy for the Detection of Stage II-III Breast Cancer: A Pilot Study
Breast cancer is the second leading cause of cancer death in women, and is the most frequently diagnosed cancer among women. The most common method for breast cancer screening is mammography, which is an x-ray of the breast. Although a mammogram may find tumors that are too small to feel, it has limitations as a screening test. These include the use of x-ray radiation and uncomfortable compression of an individuals breast. Also, the ability of a mammogram to find breast cancer may depend on the size of the tumor, the density of the breast tissue, and the skill of the radiologist. Mammograms are less likely to find breast tumors in women younger than 50 years than in older women. This may be because younger women have denser breast tissue that appears white on a mammogram resulting in missed cancers or in the discovery of later stage cancers. Light-scattering spectroscopy (LSS) is based on the science of diffusion in which light is scattered from its point of origin and interacts with another medium. When a beam of light comes into contact with an object, the light is absorbed, reflected, and/or scattered. After the light has been scattered, the measurements can be collected and analyzed. Recent advances have allowed for the noninvasive detection of precancerous lesions by using LSS. This approach has been validated for detection of precancerous polyps in the colon and pancreatic cancer.We propose a pilot study to predict the presence of breast cancer through the assessment of the tissue in the nipple using LSS, thereby eliminating the need for any direct examination or radiographic imaging of the inside of the breast. The objective of this study is to evaluate whether LSS can reliably distinguish between two subject groups: those with clinical confirmed stage II or stage III breast cancer and those without breast cancer. If successful, this technology could lead to a safer, less expensive method of breast cancer screening.Patients who agree to take part will have two assessments with the LSS probe done on each breast. They will not be followed after the assessments and their participation will end once the assessments have been completed.The data will be coded, classified, and ranked for each group. These results will be compared to the tumor status of each breast and the number of correct classifications counted. The accuracy of the classifications will be associated with the ability of the device to predict the presence of disease. Optical markers will also be analysed using multivariate analyses. The results will be evaluated and will be used to determine if the device warrants further investigation in this type of cancer.
A Phase II-R and a Phase III Trial Evaluating Both *Erlotinib (PH II-R) and Chemoradiation (PH III) as Adjuvant Treatment For Patients With Resected Head of Pancreas Adenocarcinoma
I. To determine whether the addition of erlotinib (erlotinib hydrochloride) to gemcitabine
(gemcitabine hydrochloride) adjuvant chemotherapy shows a signal for improved survival as
compared to gemcitabine alone following R0 or R1 resection of head of pancreas
adenocarcinoma (including adenocarcinoma of the head, neck, and uncinate process). (Phase
II-R) II. To determine whether the use of concurrent fluoropyrimidine and radiotherapy
following adjuvant gemcitabine hydrochloride-based chemotherapy further enhances survival
for such patients who are without evidence of progressive disease after 5 cycles of
gemcitabine based chemotherapy. (Phase III)
I. To evaluate disease-free survival of adjuvant chemotherapy followed by radiotherapy and
concurrent fluoropyrimidine for patients with resected head of pancreas adenocarcinoma who
are disease free after 5 cycles of adjuvant chemotherapy.
II. To evaluate disease-free survival of standard adjuvant gemcitabine chemotherapy with and
without erlotinib for patients with resected head of pancreas adenocarcinoma.
III. To evaluate adverse events with and without erlotinib for patients with resected head
of pancreas adenocarcinoma.
IV. To evaluate adverse events of adjuvant chemotherapy with or without radiation therapy
and concurrent fluoropyrimidine for patients with resected head of pancreas adenocarcinoma
who are disease free after adjuvant chemotherapy.
V. To evaluate preoperative cross-sectional imaging of the primary head of pancreas
adenocarcinoma in order to determine the frequency with which objective criteria of
resectability are present.
VI. To determine if patients reporting low baseline fatigue, as measured by the Functional
Assessment of Chronic Illness Therapy (FACIT)-Fatigue, predicts survival and to explore
correlations between baseline fatigue, as measured by Patient-Reported Outcomes Measurement
Information System (PROMIS), and survival.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on days
1, 8, and 15. Treatment repeats every 28 days for 5 courses in the absence of disease
progression or unacceptable toxicity.
ARM II: Patients receive gemcitabine hydrochloride as in arm I and erlotinib hydrochloride
orally (PO) once daily on days 1-28. Treatment repeats every 28 days for 5 courses in the
absence of disease progression or unacceptable toxicity. (NOTE: Phase II-R erlotinib
hydrochloride randomization completed, Arm 2 closed to accrual effective 2/19/2014)
Patients with no disease progression after treatment in arm I or II are then stratified
according to their first randomization treatment arm (arm I vs arm II) and randomized to 1
of 2 additional treatment arms (arm III or IV).
ARM III: Patients receive 1 course of the same treatment that they receive in arm I or II.
ARM IV: Patients receive 1 course of the same treatment that they receive in arm I or II.
Beginning within 7-21 days after completion of chemotherapy, patients undergo radiotherapy
(3-dimensional conformal radiotherapy or intensity-modulated radiotherapy) 5 days per week
for 5.5 weeks (28 fractions). During radiotherapy, patients receive either capecitabine PO
twice daily (BID) 5 days per week or fluorouracil IV continuously for 5.5 weeks or until
radiotherapy is completed.
After completion of study treatment, patients are followed up periodically.
0C-14-7: A Phase 1/2A, Multicenter, Open-Label Study of Oral RxDx-101 in Adult Patients with Locally Advanced or Metastatic Cancer Confirmed to be Positive for TRKA, TRKB, TRKC, ROS1, or ALK Molecular Alterations
RXDX-101-01 is a multicenter, open-label, Phase 1/2a study in which the safety and efficacy of RXDX-101 will be evaluated in adult patients with any locally advanced or metastatic solid tumor.
The primary objective of the Phase 2a expansion cohorts is Objective Response (OR) defined as Complete Response(CR) and Partial Response (PR) at the recommended phase 2 dose of RXDX-101.
RXDX-101 is an orally available inhibitor of the tyrosine kinases TrkA, TrkB, TrkC, ROS1, and ALK. Molecular alterations to these targets are present in several different tumor types, including non-small cell lung cancer, colorectal cancer, papillary thyroid cancer, pancreatic cancer, and neuroblastoma.
The Phase 2a segment of this study will consist of 5 cohorts as described below:
Cohort #1: Participants that express TrkA. Cohort #2: Participants that express TrkB. Cohort #3: Participants that express TrkC. Cohort #4a: Participants that express ALK with an associated molecular alteration who are nave to prior treatment with ALK inhibitors. Cohort #4b: Participants that express ALK with an associated molecular alteration who have received prior treatment with one or more ALK inhibitors. Cohort #5: Participants that express ROS1
USC will only participate in Phase 2 of the study. The length of participation is about 2 months
An End of Treatment Visit will be conducted within 7 days of last dose of RXDX-101.
A Safety Follow-Up telephone call will be conducted approximately 30 days following the last dose of RXDX-101.
Primary endpoint will be first cycle dose limiting toxicities and maximum tolerated dose
The baseline, clinical outcome, laboratory, PK, and safety data from both segments of the study will be analyzed descriptively
0C-10-4: A Phase Ia/Ib Clinical Trial of PRI-724 in Patients with Advanced Solid Tumors
Despite recent progresses in directed chemotherapy, the modern anti-cancer armamentarium only eradicates the majority of drug-sensitive and differentiated tumor cells. Unfortunately, to date no effective therapeutic solution has been developed to treat cancer stem cells. Based on pre-clinical research utilizing CREB-binding proteins/ beta-catenin antagonists, it is hypothesized that such antagonists can target CSCs and thereby offer a novel anti-tumor therapeutic approach.This is a Phase Ia/Ib clinical trial of PRI-724 in patients with advanced solid tumors. It has 2 arms:Phase Ia Accelerated Phase/Dose Escalation and Phase Ib Dose Expansion: PRI-724 MTDThe primary objective of the study is to determine the maximally tolerated dose (MTD) of PRI-724 when administered as a continuous 7-day intravenous infusion to patients with solid tumors. This has been completed in Phase 1a of the study. The Phase 1b will determine the MTD of PRI-274 when combined with mFOLFOX6 in patients with colorectal carcinoma.The secondary objectives are to describe the side effects experienced in both parts of the study, determine the pharmacokinetic profile of PRI-724 and C-82, assess anti-tumor activity, assess the genetic expression of survivin and the effect PRI-724 has on survivin, and assess the affect of C-82 on hair follicle neogenesis and collagen expression. The study also has an exploratory objective to obtain matrix metalloproteinase-7 (MMP7) levels in serum via enzyme-linked immunosorbent assay (ELISA) testing.The starting dose and dose escalation scheme was selected to provide an adequate safety margin based on Good Laboratory Practices (GLP) 28-day continuous iv infusion nonclinical studies. The study consists of accelerated Phase Ia and dose escalation at standard 3+3 phase. Each cycle is defined as 7-day continuous intravenous (iv) infusion followed by a 7-day rest period. At the Maximally Tolerated Dose (MTD), Phase Ib will commence where 18 patients with advanced colorectal cancer who have progressed or whose tumors are no longer responsive to standard therapies will be enrolled.The exact number of patients enrolled will depend on the toxicity observed in each dose escalation cohort and the number of cohorts required to reach MTD.The mRNA level of surviving will be measured in both Phase Ia and Ib. If mRNA level of surviving at day 8 of PRI-724 treatment is decreased 30% or more compared to the level prior to PRI-724 treatment, it suggests that PRI-724 inhibits surviving. In addition to this, assessment will be made of clinical endpoints including tumor response by RECIST and progression-free survival by tumor specimen and circulating tumor cells in every cohort.A typical electronic data capture (EDC) system will be used for data collection.Statistical analysis will be carried out by USC Norris Comprehensive Cancer Center Biostatistics core using SAS Version 9.0 or later.
0S-15-5 A Pilot Multi-Arm Study of sEphB4-HSA In Combination with Different Chemotherapy Regimens in Patients with Specific Advanced or Metastatic Solid Tumors
I. To document the safety and tolerability of sEphB4-HSA (recombinant ephB4-HSA fusion
protein) intravenously (IV) weekly when administered in combination with: arm A) gemcitabine
(gemcitabine hydrochloride) and nab-paclitaxel (paclitaxel albumin-stabilized nanoparticle
formulation), arm B) docetaxel, arm C) gemcitabine and cisplatin.
I. To describe the adverse event profile of sEphB4-HSA IV weekly when administered in
combination with: arm A) gemcitabine and nab-paclitaxel, arm B) docetaxel, arm C)
gemcitabine and cisplatin.
II. To characterize the pharmacokinetics of sEphB4-HSA when combined with: arm A)
gemcitabine and nab-paclitaxel, arm B) docetaxel, arm C) gemcitabine and cisplatin.
III. To assess, in a preliminary fashion, the anti-tumor efficacy of sEphB4-HSA in
combination with the various chemotherapy regimens in each of the 4 cohorts separately: Arm
A cohort 1-patients with advanced pancreatic cancer; Arm B cohort 2-patients with head and
neck cancer; Arm B cohort 3-patients with non-small cell lung cancer; Arm C cohort 3:
patients with cholangiocarcinoma.
I. To evaluate the expression of EPH receptor B4 (EphB4) and ephrinB2 in the archival tumor
samples and explore potential associations with outcome.
II. To bank specimens for future correlative biomarkers studies based on the results of
ongoing biomarkers analyses in the phase I of sEphB4-HSA as a single agent.
OUTLINE: This is a dose de-escalation study of recombinant EphB4-HSA fusion protein.
Patients are assigned to 1 of 3 treatment arms.
ARM A: Patients receive recombinant EphB4-HSA fusion protein IV over 1 hour on days 1, 8,
15, and 22 (beginning course 2), paclitaxel albumin-stabilized nanoparticle formulation IV
over 30 minutes and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15.
Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
ARM B: Patients receive recombinant EphB4-HSA fusion protein IV over 1 hour on days 1, 8,
and 15 (beginning course 2) and docetaxel IV over 1 hour on day 1. Courses repeat every 21
days in the absence of disease progression or unacceptable toxicity.
ARM C: Patients receive recombinant EphB4-HSA fusion protein IV over 1 hour on days 1, 8,
and 15 (beginning course 2), cisplatin IV over 120 minutes and gemcitabine hydrochloride IV
over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease
progression or unacceptable toxicity.
In all arms, patients with chemotherapy related toxicity may continue treatment with
recombinant EphB4-HSA fusion protein alone. Patients with toxicity related to recombinant
EphB4-HSA fusion protein may continue treatment with chemotherapy at the discretion of the
After completion of study treatment, patients are followed up periodically.