Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Paclitaxel

Albumin-Bound Paclitaxel

Nilotinib

Taxane

Tubulin Modulators

Antimitotic Agents

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Nilotinib will be administered at 300 mg orally BID; Paclitaxel will be administered IV at 80 mg/m2 on Days 1, 8, and 15 in 28-day cycles.

The BCR-Abl kinase inhibitor nilotinib demonstrated greater than additive activity in combination with the anti-tubulin agent paclitaxel in preclinical xenograft models, justifying the clinical evaluation of this combination for its antitumor activity

Nilotinib and Paclitaxel

Brooksley Augustine

Alice P Chen, M.D.

For more information at the NIH Clinical Center contact National Cancer Institute Referral Office

Background:

People with rare cancers often have limited treatment options. The biology of rare cancers is not well understood. Researchers want to find better treatments for these cancers. They want to test 2 drugs that, taken separately, have helped people with non-rare cancers. They want to see if these drugs together can make rare cancers shrink or stop growing.

Objective:

To learn if nilotinib and paclitaxel will benefit people with rare cancers.

Eligibility:

People age 18 and older who have a rare, advanced cancer that has progressed after receiving standard treatment, or for which no effective therapy exists.

Design:

Participants will be screened with medical history and physical exam. They will have blood and urine tests. They will have a pregnancy test if needed. They will have an electrocardiogram to check their heart. They will have imaging scans to measure their tumors.

Participants will repeat the screening tests during the study.

Participants will receive nilotinib and paclitaxel. The drugs are given in 28-day cycles. Nilotinib is a capsule taken by mouth twice a day. Paclitaxel will be given intravenously by peripheral line or central line once a week for the first 3 weeks of each cycle.

Participants will keep a medicine diary. They will track when they take the study drugs and any side effects they may have.

Participants may have optional tumor biopsies.

Participants can stay on the study until their disease gets worse or they have intolerable side effects.

Participants will have a follow-up phone call about 30 days after taking the last dose of study drugs.

Background:

* Rare tumors constitute a heterogeneous group of cancers associated with limited treatment options and poor outcomes. Due to their rarity, there are few good models for these diseases to support preclinical evaluation of new anticancer agents. To address these challenges, DCTD s Patient-Derived Models Repository (PDMR) is generating patient-derived xenograft models of adult and pediatric rare cancers and has screened combinations of approved and investigational anticancer agents in these models.
* Based on preclinical activity, drug combinations are being tested in patients with rare cancers in a series of connected Phase 2 clinical trials (Rapid Analysis and Response Evaluation of Combination Anti-Neoplastic Agents in Rare Tumors \[RARE CANCER\]); responses may trigger further evaluation of a treatment in that rare cancer type to further evaluate response rate and mechanism-of-action. Patients who progress will be offered another RARE CANCER trial.
* The agents used in this trial are the BCR-Abl kinase inhibitor nilotinib and the anti-tubulin agent paclitaxel, which showed greater than additive activity in combination in preclinical xenograft models and subsequently demonstrated clinical efficacy (including partial responses) in patients with solid tumors on the Phase 1 trial 15-C-0086 (NCT02379416).

Primary Objectives:

- To evaluate the proportion of patients with advanced rare cancers who have objective responses (OR) to treatment with nilotinib and paclitaxel

Exploratory Objectives:

* To evaluate the proportion of patients alive and progression free at 6 months on study agents
* To identify genomic and transcriptomic determinants of response and resistance in tumor biopsy specimens
* To examine genomic alterations in circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) that may be associated with response or resistance
* To evaluate the pharmacodynamic effects of the combination on biomarkers of cell death and epithelial-to-mesenchymal transition in tumor tissue and CTCs

Eligibility:

* Study participants must have a histologically confirmed solid tumor meeting the RARECARE definition of rare tumor that has progressed on standard therapy known to prolong survival or for which no standard treatment options exist
* Age \>= 18
* No major surgery, radiation, or chemotherapy within 3 weeks prior to entering the study (6 weeks for nitrosoureas and mitomycin C) or 5 half-lives of the agent, whichever is shorter; toxicity from prior treatment must have recovered to eligibility levels.
* Adequate organ function; performance status ECOG 0-2

Study Design:

* Nilotinib will be administered at 300 mg orally BID and paclitaxel will be administered IV at 80 mg/m2 on Days 1, 8, and 15 in 28-day cycles.
* A single-stage design will be used with a target accrual of 30 eligible patients. If at least 4/30 patients experience an objective response (PR or CR by RECIST 1.1), the combination of nilotinib and paclitaxel will be considered promising. The accrual ceiling is 34 patients.

Rapid Analysis and Response Evaluation of Combination Anti-Neoplastic Agents in Rare Tumors (RARE CANCER) Trial: RARE 1 Nilotinib and Paclitaxel

If at least 4/30 patients experience an objective response, defined as a complete or partial response by RECIST 1.1, the combination of nilotinib and paclitaxel will be considered promising. This design provides approximately 88% power to reject a null ORR of 0.05 when the true ORR is 0.2 (with one-sided type-I error of approximately 0.062).

National Cancer Institute (NCI)

Neoplasms

All Conditions

Rare Diseases

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Neuroendocrine Tumor

Neuroepithelioma

Antirheumatic Agents

Cyclophosphamide

Sorafenib

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Patients will receive sorafenib and cyclophosphamide.

During a run-in period, patient will start taking 50 mg QD of oral cyclophosphamide and 200 mg BID of sorafenib. On day 8 of run-in the patient will be evaluated for toxicity. In the absence of toxicity, the patient will be escalated to sorafenib 400 mg BID and continue on daily 50 mg of cyclophosphamide, or the patient will be informed to continue on sorafenib 200 mg BID and cyclophosphamide 50 mg QD. Dose escalation procedure will be repeated every 2 weeks until unable to tolerate the study drug, or a maximum of 800 mg BID is reached, or achievement of \> 90% inhibition of phosphorylation of PDGFR/Raf axis in PBMC. After "run-in" period, patient begins cycle 1, each cycle will last 28 days. Both cyclophosphamide and sorafenib will be taken orally.

Lillian Siu, MD

This is a phase II clinical trial to assess the efficacy of the combination of metronomic cyclophosphamide and tailored sorafenib dosing in advanced, progressive NET. NET are highly vascular tumors, and high VEGF expression has been correlated with worse clinical and pathological characteristics as well as poor prognosis. A novel antiangiogenic approach relies on targeting not only the endothelial cells but also rendering them more sensitive to VEGFR blockade by achieving pericyte detachment. In this study, the dose of sorafenib will be titrated up to a maximum of 800mg BID based on patients' toxicity and on a novel pharmacodynamic assay that measures inhibition of molecular target(PDGFR) in patients' peripheral blood mononuclear cells. Dual VEGFR targeting is achieved by administering sorafenib plus metronomic low dose cyclophosphamide.

Efficacy Study of Sorafenib and Cyclophosphamide to Treat Neuroendocrine Tumors

Tailored-dose Sorafenib Plus Metronomic Cyclophosphamide in Advanced Neuroendocrine Tumors (NET): a Phase II Clinical Trial Based on Individual Pharmacodynamic Assessment

Objective response (complete and partial) evaluated using RECIST criteria. Complete response (CR): disappearance of all clinical and radiological evidence of tumour (both target and non-target).

Partial response (PR): at least a 30% decrease in the sum of longest diameter of target lesions.

A phosphoshift (pShift) flow cytometry-based test that measures RAF signal transduction capacity in peripheral blood cells was used in order to predict clinical course and/or guide individual dose-titration. Positive pShift values denote stimulation of RAF signal transduction, whereas negative pShift values denote inhibition of RAF signal transduction as measured by flow-cytometry.

Associations between pShift changes and treatment efficacy were measured using progression-free survival (PFS) and overall survival (OS).

Progressive disease (PD): at least a 20% increase in the sum of the longest diameter of measured lesions.

University Health Network, Toronto

Patients will receive sorafenib and cyclophosphamide.

sorafenib and cyclophosphamide: During a run-in period, patient will start taking 50 mg QD of oral cyclophosphamide and 200 mg BID of sorafenib. On day 8 of run-in the patient will be evaluated for toxicity. In the absence of toxicity, the patient will be escalated to sorafenib 400 mg BID and continue on daily 50 mg of cyclophosphamide, or the patient will be informed to continue on sorafenib 200 mg BID and cyclophosphamide 50 mg QD. Dose escalation procedure will be repeated every 2 weeks until unable to tolerate the study drug, or a maximum of 800 mg BID is reached, or achievement of \> 90% inhibition of phosphorylation of PDGFR/Raf axis in PBMC. After "run-in" period, patient begins cycle 1, each cycle will last 28 days. Both cyclophosphamide and sorafenib will be taken orally.

Sorafenib Plus Cyclophosphamide

Age, Categorical

Age, Continuous

Sex: Female, Male

Dr. Lillian Siu

Sorafenib and Cyclophosphamide

19 out of 22 patients were evaluable for response.

Efficacy of Combination Sorafenib Plus Metronomic Cyclophosphamide in Advanced, Progressive NET, as Measured by the Objective Response Rate (ORR).

PFS in patients with a negative pShift result

PFS in patients with a positive pShift result

OS for patients with a negative pShift

OS for patients with a positive pShift

6 patients experienced a pharmacodynamic pShift change that was classified as positive, 16 experienced a negative pShift.

Association Between p-Shift Changes and Treatment Efficacy of Individual Dose Adjustment of Sorafenib

Progression-free Survival (PFS)

Overall Survival (OS)

1-year Survival Rate

Overall Study

Symptoms and General Pathology

Skin and Connective Tissue Diseases

Hemorrhage

Leiomyoma

Myofibroma

Neoplasms, Connective and Soft Tissue

Neoplasms, Connective Tissue

Connective Tissue Diseases

Reproductive Control Agents

Ulipristal acetate

Contraceptive Agents

Contraceptive Agents, Hormonal

Contraceptive Agents, Female

Vilaprisan 2 mg oral daily over 8-12 weeks

Ulipristal 5 mg oral daily over 8-12 weeks

Patients undergoing surgery without any prior treatment, as control group

Daily single oral doses of 2 mg vilaprisan over 8-12 weeks

Vilaprisan, BAY1002670

Daily single oral doses of 5 mg ulipristal over 8-12 weeks

Ulipristal

Bayer Study Director

To investigate the clinical effects of vilaprisan and ulipristal acetate at molecular and cellular level on uterine and fibroid tissue taken from patients (after surgery / biopsy)

Mode of Action Study of Vilaprisan and Ulipristal Acetate in Patients With Uterine Fibroids for Whom Surgery is Planned

An Open-label, Parallel Group, Multi-center Study to Investigate Pharmacodynamic Effects After Daily Administration of Vilaprisan or Ulipristal Acetate for 8-12 Weeks in Patients With Uterine Fibroids for Whom Surgery (Hysterectomy or Myomectomy) is Planned

Pre-treatment biopsy: The endometrial biopsy will be performed between Day 6 to 13 of the menstrual cycle that occurs after the screening visit and before treatment commences. Post-treatment biopsy as second endometrial biopsy is taken (if possible within 24 hours) after end of VPR treatment.

Fibroid tissue sample will be collected from the uterus following surgery (if possible within 24 hours) after end of VPR treatment

Pre-treatment biopsy: The endometrial biopsy will be performed between Day 6 to 13 of the menstrual cycle that occurs after the screening visit and before treatment commences. Post-treatment biopsy as second endometrial biopsy is taken (if possible within 24 hours) after end of VPR treatment

Pre-treatment biopsy: The endometrial biopsy will be performed between Day 6 to 13 of the menstrual cycle that occurs after the screening visit and before treatment commences. Post-treatment biopsy as second endometrial biopsy is taken (if possible within 24 hours) after end of treatment. Fibroid tissue sample will be collected from the uterus following surgery (if possible within 24 hours) after end of treatment

Bayer

Shock

Dr Udai Banerji

The principal research objective of this additional research protocol is to support the collection, storage and use of tumour and surrogate (peripheral blood mononuclear cells - PBMNCs). The objective of this study is to perform assays to study pharmacodynamic (PD) markers that confirm target modulation.

Study objectives -

1. Evaluation of HSP70, p-ERK, ERK, p-AKT and AKT in peripheral blood mononuclear cells (PBMNC). Evaluation of p-AKT and AKT will be done by commercially available Meso Scale Discovery (MSD) enzyme linked immunosorbent assay (ELISA) kits, while HSP70 will be studied using ELISA techniques developed within the Institute of Cancer Research.
2. Evaluation of HSP70, p-AKT, AKT, p-ERK, ERK, HER-2 and p-HER2 in tumour tissue. Evaluation of p-AKT, AKT, p-ERK, ERK, HER-2 and p-HER2 will be done by commercially available MSD ELISA kits, while HSP70 will be studied using ELISA techniques developed within the Institute of Cancer Research.

Study design - All patients entering the open label, phase I dose escalation and phase II expansion arms of AUY922A at the Royal Marsden Hospital will be asked to participate in this study. Patients will not have to attend additional appointments for this study and samples will be taken during visits for the planned Phase I/II clinical trial. Consent to donate samples for this research study is voluntary and patients will be asked to sign a separate consent form.

Analysis of Pharmacodynamic Changes With AUY922A, an HSP90 Inhibitor

Analysis of Pharmacodynamic Changes Associated With the Administration of the Heat Shock Protein 90 Inhibitor AUY922A in Patients With Advanced Solid Malignancies

Institute of Cancer Research, United Kingdom

Royal Marsden NHS Foundation Trust

Cisplatin

Poly(ADP-ribose) Polymerase Inhibitors

Veliparib

M6620 will be administered intravenous (IV) on Days 2 and 9 of each 21-day cycle; Veliparib will be administered orally twice a day (BID) Days 1-3 and 8-10 of each cycle; Cisplatin will be administered at 40 mg/m\^2 IV Day 1 (and Day 8 from dose level 3 onwards) of each cycle

Ataxia-telangiectasia-related (ATR) protein kinase is central to the deoxyribonucleic acid (DNA) damage response and homologous recombination, activating a series of phosphorylation cascades, culminating in cell cycle arrest to allow time for DNA repair. Poly (ADP-ribose) polymerase (PARP) plays a pivotal role in base-excision repair of single strand breaks formed either due to direct genotoxic stress or during the processing of double strand breaks. Preclinical studies show ATR inhibitor M6620 (VX-970) synergizes with cisplatin to induce DNA damage and antitumor activity. The addition of PARP inhibitor veliparib with VX-970 allows for impairment of DNA repair, induction of a breast cancer gene (BRCA) null phenotype, and potentiation of the antitumor activity of cisplatin.

Veliparib + VX-970 + Cisplatin

Background:

The drug cisplatin treats certain cancers when given with other chemotherapy drugs. Researchers think combining cisplatin with 2 other drugs could block proteins that support cancer cell growth. The other drugs are ABT-888 (veliparib) and M6620 (VX-970). They want to test if this drug combination slows the growth of cancer and is safe.

Objectives:

To test the safety and tolerability of VX-970 and veliparib combined with cisplatin in people with advanced refractory solid tumors. To determine the maximum tolerated dose of these drugs.

Eligibility:

People ages 18 and older with:

* Solid tumors that have progressed after treatment or for which no treatment exists
* Normal organ and marrow function

Design:

Participants will be screened with:

* Medical history
* Physical exam
* Computed tomography (CT) scan or magnetic resonance imaging (MRI)
* Blood and urine tests

Participants will get the study drugs in 3-week cycles:

* Cisplatin in a vein on 1 or 2 days
* VX-970 in a vein on 2 days
* Veliparib by mouth twice a day on 6 days

In each cycle, participants will have 5 physical exams and blood tests 5 times.

In some cycles, participants will have CT scans or MRIs.

In cycle 1, participants may have 2 tumor biopsies. A small piece of tissue is removed by needle.

Participants will keep a study diary. They will write when they take the drugs and if they have side effects.

Participants will stay in the study as long as they tolerate the drugs and their tumors are not getting worse.

Participants will have a phone call about a month after their last dose.

Background:

* Ataxia-telangiectasia-related (ATR) protein kinase is central to the deoxyribonucleic acid (DNA) damage response and homologous recombination, activating a series of phosphorylation cascades, culminating in cell cycle arrest to allow time for deoxyribonucleic acid (DNA) repair. ATR additionally facilitates homologous recombination repair through modulation of the p53-replication protein A (p53-RPA) complex bound to single-stranded deoxyribonucleic acid (ssDNA) during the DNA repair process.
* Poly (ADP-ribose) polymerase-1 (PARP-1) plays a pivotal role in base-excision repair of single strand breaks formed either due to direct genotoxic stress or during the processing of double strand breaks. PARP also plays a role in alternative end joining, which may contribute to combination activity. PARP-1 binding to sites of DNA damage results in activation of its catalytic activity and generation of chains of poly (ADP-ribosyl)ated polymers, which serve as docking sites for recruitment of DNA repair proteins.
* Veliparib (ABT-888) is a potent PARP 1/2 inhibitor with clinical evidence of potentiation of antitumor activity in combination with cisplatin in breast cancer gene (BRCA) mutation carriers and patients with sporadic triple-negative breast cancer.
* M6620 (VX-970) is a potent ATR inhibitor, with half maximal inhibitory concentration (IC(50) of 20 nanomolar and antitumor activity across a broad range of cell lines in combination with DNA damaging agents. Preclinical studies show M6620 (VX-970) synergizes with cisplatin to induce DNA damage and antitumor activity. The addition of PARP inhibitor veliparib with ATR inhibitor M6620 (VX-970) allows for impairment of DNA repair, the induction of a BRCA null phenotype, and potentiation of the antitumor activity of cisplatin.

Primary Objective:

-To establish the safety, tolerability, and the maximum tolerated dose (MTD) of the combination of M6620 (VX-970) and veliparib in combination with cisplatin in patients with advanced refractory solid tumors

Secondary Objectives:

* To assess the effect of the combination of M6620 (VX-970), veliparib, and cisplatin on markers of DNA damage and apoptosis
* To assess antitumor activity of the combination

Exploratory Objective:

-To investigate tumor genomic alterations potentially associated with acquired resistance to the combination of M6620 (VX-970), veliparib, and cisplatin

Eligibility:

* Patients must have histologically confirmed solid tumors for which all standard therapy known to prolong survival has failed in the metastatic setting, or for which standard therapies do not exist
* Patients must have had no major surgery, radiation, or chemotherapy within 3 weeks prior to entering the study
* Patients must have adequate organ function

Study Design:

* Initially, M6620 (VX-970) will be administered intravenously on Days 2 and 9 of each 21-day cycle. Veliparib will be administered orally twice a day (every (q)12 hours +/- 1 hour) for Days 1-3 and 8-10 of each 21-day cycle. Cisplatin will be administered at 40 mg/m\^2 intravenously on Day 1 (and Day 8 from dose level 3 (DL3) onwards) of each 21-day cycle.
* As of Amendment I (12/7/2017), patients who have been on study for at least 6 cycles may have cisplatin administration held or discontinued at the discretion of the Principal Investigator (PI), Dr. Chen, in recognition of the cumulative neurotoxicity seen with cisplatin treatment. If cisplatin is not administered during a cycle M6620 (VX-970) will be administered on Days 1 and 8 of that cycle.
* The escalation portion of the trial will follow a standard 3+3 design, whereby patients will be dose escalated in cohorts of 3 until dose-limiting toxicity is observed
* Once the maximum tolerated dose (MTD) is established, up to 15 additional patients will be enrolled to an expansion phase at the MTD. Mandatory tumor biopsies will be obtained in the expansion phase to assess pharmacodynamic (PD) endpoints

Veliparib (ABT-888), an Oral PARP Inhibitor, and VX-970, an ATR Inhibitor, in Combination With Cisplatin in People With Refractory Solid Tumors

Phase I Study of Veliparib (ABT-888), an Oral PARP Inhibitor, and VX-970, an ATR Inhibitor in Combination With Cisplatin in Patients With Refractory Solid Tumors

We will share IPD (clinical data) during the study and indefinitely via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI).

Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Adverse events were assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Grade 2 is moderate, Grade 3 is severe or medically significant but not immediately life threatening, and Grade 4 is life threatening.

Biopsies were collected at Cycle 1 Day 1, and Cycle 1 Day 9 and markers Rad51, γH2AX, pS343-Nbs1, and pKAP-1 were measured for deoxyribonucleic acid (DNA) damage and apoptosis by immunofluorescence assays (IFA).

Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Complete Response (CR) is disappearance of all target lesions. Partial Response (PR) is at least a 30% decrease in the sum of the diameters of target lesions. Progressive Disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, and the appearance of one or more new lesions. Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

Principal Investigator

DL 1: ABT-888 100 mg by mouth (PO) every (Q)12 hours on days 1-3 \& 8-10, VX-970 90 mg/m\^2 intravenous (IV) over 1 hour days 2 \& 9, Cisplatin 40 mg/m\^2 IV over 1hr day 1 (optional after 6 cycles)

Dose Level 1

DL 2: ABT-888 100 mg by mouth (PO) every (Q)12 hours on days 1-3 \& 8-10, VX-970 140 mg/m\^2 intravenous (IV) over 1 hour days 2 \& 9, Cisplatin 40 mg/m\^2 IV over 1hr day 1 (optional after 6 cycles)

Dose Level 2

DL 3: ABT-888 100 mg by mouth (PO) every (Q)12 hours on days 1-3 \& 8-10, VX-970 120 mg/m\^2 intravenous (IV) over 1 hour days 2 \& 9, Cisplatin 40 mg/m\^2 IV over 1hr days 1 \& 8 (optional after 6 cycles)

Dose Level 3

DL 4: ABT-888 100 mg by mouth (PO) every (Q)12 hours on days 1-3 \& 8-10, VX-970 210 mg/m\^2 intravenous (IV) over 1 hour days 2 \& 9, Cisplatin 40 mg/m\^2 IV over 1hr days 1 \& 8 (optional after 6 cycles)

Dose Level 4

DL 5: ABT-888 150 mg by mouth (PO) every (Q)12 hours on days 1-3 \& 8-10, VX-970 210 mg/m\^2 intravenous (IV) over 1 hour days 2 \& 9, Cisplatin 40 mg/m\^2 IV over 1hr days 1 \& 8 (optional after 6 cycles)

Dose Level 5

DL 6: ABT-888 200 mg by mouth (PO) every (Q)12 hours on days 1-3 \& 8-10, VX-970 210 mg/m\^2 intravenous (IV) over 1 hour days 2 \& 9, Cisplatin 40 mg/m\^2 IV over 1hr days 1 \& 8 (optional after 6 cycles)

Dose Level 6

DL 7: ABT-888 300 mg by mouth (PO) every (Q)12 hours on days 1-3 \& 8-10, VX-970 210 mg/m\^2 IV over 1 hour days 2 \& 9, Cisplatin 40 mg/m\^2 intravenous (IV) over 1hr days 1 \& 8 (optional after 6 cycles)

Dose Level 7

Total

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

ECOG 0

ECOG 1

ECOG 2

ECOG performance status 0 is fully active. ECOG performance status 1 is symptoms but ambulatory. ECOG performance status 2 is in bed \<50% of the time.

Eastern Cooperative Oncology Performance Status (ECOG)

Lung cancer

Ovarian cancer

Liver cancer

Uterine cancer

Pancreatic cancer

Peritoneal cancer

Breast cancer

Colon cancer

Esophageal cancer

Other

Diagnosis: Tumor Type

Dr. Alice Chen

Alkaline phosphatase increased

Anemia

Creatinine increased

Fatigue

Hypertension

Hypomagnesemia

Hyponatremia

Hypophosphatemia

Infusion related reaction

Lymphocyte count decreased

Nausea

Neutrophil count decreased

Peripheral sensory neuropathy

Platelet count decreased

Proteinuria

Thromboembolic event

White blood cell decreased

Grade 2 Adverse Events - Dose Level 1

Grade 3 Adverse Events - Dose Level 1

Grade 4 Adverse Events - Dose Level 1

Grade 2 Adverse Events - Dose Level 2

Grade 3 Adverse Events - Dose Level 2

Grade 4 Adverse Events - Dose Level 2

Grade 2 Adverse Events - Dose Level 3

Grade 3 Adverse Events - Dose Level 3

Grade 4 Adverse Events - Dose Level 3

Grade 2 Adverse Events - Dose Level 4

Grade 3 Adverse Events - Dose Level 4

Grade 4 Adverse Events - Dose Level 4

Grade 2 Adverse Events - Dose Level 5

Grade 3 Adverse Events - Dose Level 5

Grade 4 Adverse Events - Dose Level 5

Grade 2 Adverse Events - Dose Level 6

Grade 3 Adverse Events - Dose Level 6

Grade 4 Adverse Events - Dose Level 6

Grade 2 Adverse Events - Dose Level 7

Grade 3 Adverse Events - Dose Level 7

Grade 4 Adverse Events - Dose Level 7

Number of Participants With Worst Grade 2 or Higher Adverse Events Occurring in >5% of Participants at Least Possibly Related to Study Drugs

Rad51 induced after veliparib and cisplatin treatment on Cycle 1, Day 1

Rad51 induced after veliparib, cisplatin and M6620 treatment on Cycle 1, Day 9

These measurements were only carried out on the subset (7/25) of DL6 participants from whom evaluable C1D1 and C1D9 biopsies were collected.

Number of Participants With RAD51 Recombinase (Rad51), Phosphorylated Histone H2AX (γH2AX), Phosphorylated at Serine 343 (pS343)-Nibrin (Nbs1), and Phosphorylated KRAB-associated Protein 1 (pKAP-1) Induced After Treatment

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Rapid Analysis and Response Evaluation of Combination Anti-Neoplastic Agents in Rare Tumors (RARE CANCER) Trial: RARE 1 Nilotinib and Paclitaxel	NCT04449549	Neoplasms	Nilotinib and P...	18 Years - 120 Years	National Institutes of Health Clinical Center (CC)
Efficacy Study of Sorafenib and Cyclophosphamide to Treat Neuroendocrine Tumors	NCT00605566	Neuroendocrine ...	Sorafenib Cyclophosphamid...	18 Years -	University Health Network, Toronto
Mode of Action Study of Vilaprisan and Ulipristal Acetate in Patients With Uterine Fibroids for Whom Surgery is Planned	NCT03342859	Leiomyoma	Vilaprisan, BAY... Ulipristal	18 Years -	Bayer
Analysis of Pharmacodynamic Changes With AUY922A, an HSP90 Inhibitor	NCT01024283	Advanced Solid ...		16 Years -	Royal Marsden NHS Foundation Trust
Veliparib (ABT-888), an Oral PARP Inhibitor, and VX-970, an ATR Inhibitor, in Combination With Cisplatin in People With Refractory Solid Tumors	NCT02723864	Neoplasms	Veliparib + VX-...	18 Years -	National Institutes of Health Clinical Center (CC)
POEM STUDY: A Phase IIa Trial in Endometrial Carcinoma With Temsirolimus	NCT02093598	Carcinoma, Endo... mTOR Protein	Temsirolimus	18 Years -	MedSIR
Rapid Analysis and Response Evaluation of Combination Anti-Neoplastic Agents in Rare Tumors (RARE CANCER) Trial: RARE 1 Nilotinib and Paclitaxel	NCT04449549	Neoplasms	Nilotinib and P...	18 Years - 120 Years	National Institutes of Health Clinical Center (CC)
Erlotinib in Combination With Select Tyrosine Kinase Inhibitors in Adult Patients With Advanced Solid Tumors	NCT06161558	Neoplasms	Erlotinib Lenvatinib Axitinib	18 Years - 120 Years	National Institutes of Health Clinical Center (CC)
Mode of Action Study of Vilaprisan and Ulipristal Acetate in Patients With Uterine Fibroids for Whom Surgery is Planned	NCT03342859	Leiomyoma	Vilaprisan, BAY... Ulipristal	18 Years -	Bayer
Repeat-Dose Pharmacokinetics and Pharmacodynamics of Bortezomib in Patients With Relapsed Multiple Myeloma	NCT00080405	Multiple Myelom...	Bortezomib	18 Years -	Millennium Pharmaceuticals, Inc.
Mode of Action Study of Vilaprisan and Ulipristal Acetate in Patients With Uterine Fibroids for Whom Surgery is Planned	NCT03342859	Leiomyoma	Vilaprisan, BAY... Ulipristal	18 Years -	Bayer

Spots Global Cancer Trial Database for pharmacodynamic