Symptoms and General Pathology

All Conditions

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Hypoxia

Uterine Cervical Neoplasms

Carcinoma, Renal Cell

Uterine Neoplasms

Kidney Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urologic Neoplasms

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

Micronutrients

Anti-Infective Agents

All Drugs and Chemicals

Iodine

Cadexomer iodine

Patients will receive 124IAZGP(124I-Iodo-Azomycin Galacto-Pyranoside).

You will receive the radioactive tracer through an injection in your vein. Blood (about 5 tablespoons in all) will be taken after the radioactive tracer has been given. Over the course of study day 1, bloods will be drawn 8 times and then 4 more times on study day 2. You will undergo three \*IAZGP PET scans, one shortly after you receive the injection, one later the same day and one the following day. Each scan will take about an hour. This means you would be asked to come back 2 days in a row.

124I-Iodo-Azomycin Galacto-Pyranoside

Heiko Schöder, MD

The purpose of this study is to evaluate low oxygen areas called hypoxia within the tumor. These low oxygen areas are thought to be the reason why tumors are more resistant to radiation treatment. A tracer is an extremely small quantity of a substance. Tracer to which radioactivity has been attached may be used to "trace" events in the body. A tracer called iodo-azomycin galactopyranoside (or \*IAZGP) appears to be able to detect low oxygen areas within tumor.

Radioactive iodine in this molecule can be detected by an imaging technique called a PET scan. This present study involves obtaining three scans using this new imaging technique. The goal of carrying out many scans is to determine which scan will best show any areas in your tumor that may have low levels of oxygen.

Pilot Evaluation of 124I-Iodo-Azomycin Galacto-Pyranoside (*IAZGP) Positron Emission Tomography (PET) in the Imaging of Hypoxic Tumors

National Cancer Institute (NCI)

Memorial Sloan Kettering Cancer Center

Neoplasm Metastasis

Carcinoma

Recurrence

Urinary Bladder Neoplasms

Carcinoma, Transitional Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Urinary Bladder Diseases

Transitional Cell Carcinoma

Camurati-Engelmann Disease

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Mitogens

Investigational study drug, administered intravenously every 2 weeks until disease progression or unacceptable toxicity.

PF-03446962 will be administered in 1hr intravenously at a dose of 10 mg/Kg on day 1, then every 2 weeks until the evidence of disease progression or onset of unacceptable toxicity.

PF03446962

Andrea Necchi, MD

Filippo G De Braud, MD

Alessandro M Gianni, MD

Salvage chemotherapy for advanced urothelial cancer (UC) yields suboptimal response rates of 15-40%, a median progression-free survival of 2-4 months and a median overall survival of 6 months. A rationale for targeting angiogenesis in UC is supported by preclinical evidences and early signals of clinical activity of anti-VEGF TKI as demonstrated by our group with the use of pazopanib.

Despite this activity, progression inevitably occurs and mechanisms determining resistance to conventional anti-angiogenic agents are under investigation.

PF-03446962 (Pfizer Inc) is a novel fully human monoclonal antibody (mAb) against ALK1 with dose-dependent antiangiogenic activity as demonstrated in nonclinical studies in a chimera mouse model bearing human tumor xenograft. The investigators suggest that PF-03446962 may increase current results for patients with advanced urothelial cancer failing upfront chemotherapy due to its mechanisms of action. Due to the lack of reliable and reproducible predictors of response as well as of imaging tools to assess tumor response, the trial will provide incorporation of 18FDG-PET/CT and contrast-enhanced ultrasound to stage and evaluate response of urothelial cancers, together with standard imaging modalities (RECIST criteria). Blood and tissue samples will be collected for translational purposes.

This is an open-label, single arm, non randomised, phase II proof-of-concept study of the monoclonal antibody against TGF-beta receptor ALK1 (PF03446962) for patients with urothelial cancer relapsing/progressing after first line chemotherapy.

The study is planned according to Simon's Optimal two-stage design. The primary endpoint is the proportion of patients who are progression-free at 2-months. A 2-month PFS rate of 50% is not promising, while a 70% rate will be promising. In stage 1, 21 evaluable patients will be accrued. If 12 patients at least will be progression-free at 2 months, enrollment will be extended to the 2nd stage for further 24 patients. If, out of the total of 45 patients, 27 at least will be progression-free at 2 months, treatment will be declared worthy for further investigations.

Maximum overall accrual is 45 patients. Type I and type II error rates will be set both at the 10% level.

PF-03446962 in Relapsed or Refractory Urothelial Cancer

Phase II Study of the Fully Human Monoclonal Antibody Against Transforming Growth Factor-beta (TGFβ) Receptor ALK1 (PF-03446962) in Relapsed or Refractory Urothelial Cancer (UC) Failing First-line Treatment.

Progression-free survival (PFS) is defined as the interval from the first dose of study drug to the date of the first documented disease progression or death for any reason, with censoring at the date of last contact for alive patients. A patient who has not progressed or died by the date of the analysis cut-off or when the patient received any further anticancer therapy would have the PFS censored at the time of last adequate tumor assessment before either cut-off date or the commencement of further anticancer therapy date, respectively.

Incidence of adverse events (AEs), defined as any new untoward medical conditions occurrence or worsening of a pre-existing medical condition that does not necessarily have a causal relationship with the study drugs. AEs will be graded according to the NCI-CTC version 4.03 and the relationship of each AEs to study drugs will be assessed by the investigator.

Assessment of response-rate by RECIST v1.1 criteria. RR (%) = CR + PR

Overall Survival (OS) will be calculated as the interval from the date of the first dose of study drug to the date of death for any cause, with censoring at the date of last contact for patients alive. The Kaplan-Meier method will be used to estimate the OS curve (median and 95% confidence interval).

Tissue will be examined in terms of genotyping by high-resolution array comparative genome hybridization (aCGH) and expression of VEGFR, PDGFR, KIT, EGFR, HER2/neu, PTEN on tissue microarrays (TMAs).

Circulating VEGF, soluble VEGFR-1, 2 and -3, soluble c-Kit, IL-6, 8, 12 and HGF will be evaluated by using multiplex ELISA plates.

Circulating tumor cells will be evaluated as a potential response biomarkers.

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Principal Investigator

Gland and Hormone Related Diseases

Adrenocortical Carcinoma

Adrenal Cortex Neoplasms

Adrenal Gland Neoplasms

Endocrine Gland Neoplasms

Adrenal Cortex Diseases

Adrenal Gland Diseases

Endocrine System Diseases

Adenocarcinoma

Vasoconstrictor Agents

Respiratory System Agents

Antineoplastic Agents

Epinephrine

Axitinib

Racepinephrine

Epinephryl borate

Protein Kinase Inhibitors

Enzyme Inhibitors

Aggressive cancer that starts in the adrenal gland located at the top of the kidneys.

5 mg tab orally twice a day with food every 28 days

Antonio T Fojo, M.D.

Background:

- Adrenocortical carcinoma is an aggressive cancer that starts in the adrenal gland at the top of the kidneys. It has a low survival rate if standard treatment options are not effective. Axitinib is an experimental drug that is being studied to determine if it can stop tumors from growing or make them smaller. Researchers are interested in investigating axitinib in individuals with aggressive or otherwise untreatable adrenocortical cancer.

Objectives:

- To evaluate the effectiveness of axitinib in individuals who have adrenocortical cancer that is inoperable and has not responded to standard treatments.

Eligibility:

- Individuals at least 18 years of age who have been diagnosed with adrenocortical cancer that has not responded to standard treatments.

Design:

* Participants will be screened with a full physical examination and medical history, as well as tumor imaging studies.
* Participants may have a tumor biopsy prior to starting axitinib.
* All participants will receive axitinib to take twice a day with food for 28 days (1 cycle). Participants should not drink grapefruit juice or smoke cigarettes while participating in this study.
* After the first cycle, the dose may be increased and additional cycles will be given if the treatment has not had serious side effects.
* Participants will have regular examinations while taking axitinib, including blood samples and tumor imaging studies to determine if the tumor has stopped growing. Blood pressure levels will be carefully monitored during treatment to evaluate potential risk for high blood pressure.
* Participants may have a second tumor biopsy 20 to 30 days after treatment begins.
* Treatment will continue as directed by the study researchers.

Background:

* The response rates of recurrent, metastatic and unresectable adrenocortical cancer (ACC) to mitotane, doxorubicin, etoposide, and cisplatin are low and underscore the need for more effective systemic therapies.
* VEGF expression and evidence of angiogenesis has been found in many ACCs, so it is plausible that interfering with vascular endothelial growth factor(VEGF) signaling may result in anti-tumor activity in patients with ACC.
* Axitinib (AG-013736) is an oral, potent and selective inhibitor of vascular endothelial growth factor (VEGF) receptors 1, 2, and 3. Pre-clinical data suggests that the anti-tumor activity of axitinib may result from its anti-angiogenic activity and that this is reversible when treatment is discontinued.
* Given the known clinical safety and efficacy of axitinib, an assessment of its activity in ACC and its impact on the VEGF pathway in ACC could provide valuable information.

Objectives:

* Determine the response rate of axitinib (AG-013736) in recurrent, metastatic, or primary unresectable ACC
* Determine the progression-free survival
* Explore the relationship of potential biological markers of axitinib activity with clinical outcomes.
* Explore the pharmacogenetic analyses of drug metabolism and transport proteins through germline deoxyribonucleic acid (DNA) examination.

Eligibility:

* Adults with pathologic confirmation of ACC by the Laboratory of Pathology, National Cancer Institute (NCI)
* Diagnosis of recurrent, metastatic, or primary unresectable ACC
* Measurable disease at presentation
* Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2
* Patients must not have received prior therapy with a tyrosine kinase (TK) inhibitor

Design:

* Phase II, open label, non-randomized trial
* Patients with recurrent, metastatic, or primary unresectable ACC will be given in eight weeks cycles with BID dosing of axitinib (AG-013736).
* Patients will be evaluated for response every eight weeks using Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
* Tumor biopsies are not mandatory but every attempt will be made to obtain these from patients prior to starting axitinib and again 20-30 days after treatment has begun.
* Approximately 40 patients will be needed to achieve the objectives of the trial.

Phase II Study of Axitinib (AG-013736) With Evaluation of the VEGF-Pathway in Metastatic, Recurrent or Primary Unresectable Adrenocortical Cancer

Response was defined by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR) is a disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10mm. Partial response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameter. Progressive disease (PD) is a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm (Note: the appearance of one or more new lesions is also considered progression). Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking s reference the smallest sum diameters while on study.

Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse events module.

Pfizer

Aggressive cancer that starts in the adrenal gland located at the top of the kidneys.

Axitinib : 5 mg tab orally twice a day with food every 28 days

Age, Categorical

Age Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Tito Fojo

Complete Response

Partial Response

Progression

Stable Disease

Response Rate (RR) of Axitinib Administered Daily, in Patients With Recurrent, Metastatic, or Primary Unresectable Adrenocortical Cancer (ACC)

Number of Participants With Adverse Events

Overall Study

Skin and Connective Tissue Diseases

Breast Neoplasms

Triple Negative Breast Neoplasms

Breast Diseases

Skin Diseases

Androgens

Avelumab

Palbociclib

Antineoplastic Agents, Immunological

Recruitment to Part A will be conducted at the Royal Marsden Hospital only. Up to 18 patients will be recruited for dose escalation of palbociclib in combination with fixed dose avelumab.

Part B will recruit at up to 8 high volume centres. Up to 27 patients will be recruited to treatment with the maximum tolerated dose and schedule established in part A. In Part B of the study, additional selection by triple negative histology and positive androgen receptor status will define the study population.

Highly selective oral inhibitor of CDK4 and CDK6.

Fully human IgG1 monoclonal antibody (mAb) binds to the PD-L1 cell surface ligand and blocks its interaction with the PD-1 cell surface receptor.

Rebecca Ruiz

Dr Alicia Okines

Alison Musson

Anne Armstrong

Jeremy Braybrooke

Iain MacPherson

Ellie Ibbott

Peter Schmid

Alicia Okines

Juliamol Job

Sarah Khan

Caroline Wilson

Carlo Palmieri

This clinical study is aiming to determine the safest doses and schedule for the combination of two drugs named palbociclib and avelumab.

The study will also be investigating how effective the combination is for a subgroup of breast cancer patients whose cancer expresses the androgen receptor (AR) but not the oestrogen (hormone) or HER2 receptors. Palbociclib is a drug used in routine care for hormone-receptor (HR) positive and HER2 negative advanced breast cancer, the most common subtype of breast cancer.

It is possible that the combination of palbociclib and avelumab will be a more effective cancer treatment than each drug separately, but this is unknown and this study is needed to establish the best dosage and schedule of each drug as well as how effective the combination is.

This is a phase Ib study designed to confirm the safety and evaluate the efficacy of palbociclib combined with avelumab in AR positive TNBC. It is a multi-centre study design (it will run at several hospitals in the UK).

Palbociclib inhibits two proteins involved in cell growth called cyclin dependent kinase 4 and cyclin dependent kinase 6 (CDK4/6). Inhibiting CDK4/6 stops cells, such as cancer cells, from dividing and multiplying further. Palbociclib is currently approved for the treatment of metastatic HR positive HER2 negative breast cancer, based on good results from large clinical trials. Laboratory studies have shown that palbociclib might be also useful in some patients with triple negative breast cancer, an aggressive subtype of breast cancer that does not express the hormone receptors or HER2 receptor, but only if the cancer is positive for the androgen-receptor (AR).

Avelumab is an immunotherapy drug which does not destroy cancer cells, but tries to stimulate the body's immune system to do this. Avelumab has been tested in a number of different types of tumours including breast cancer, but although approved for use in the USA, it is not currently an approved standard treatment in the UK. The combination of both drugs has never been tested in humans before.

Recruitment to Part A will be conducted only at the Royal Marsden Hospital and Part A of the study will establish the maximum tolerated dose (MTD) and optimal schedule of the combination in any suitable patients with advanced breast cancer. Once this dose schedule has been confirmed, the chosen dose level will be recruited to, aiming to include 27 patients with AR positive TNBC (Part B).Part B will recruit at up to 8 high volume centres. The androgen receptor is not routinely tested for in hospital laboratories, so patients with advanced triple negative breast cancer who are interested in taking part in the study will be asked to provide consent for previously taken cancer samples/biopsies to be sent to the Royal Marsden for testing, to see if the cancer expresses the androgen receptor, which would make participants potentially eligible for part B of the study. Approximately 20% of triple negative breast cancers express AR. This phase of the study will include important translational work using new cancer samples (biopsies) and blood samples to investigate potential "biomarkers" -predictors of efficacy and resistance to the combination.

In Part A of the study, patients with previously treated, advanced breast cancer will have an ECG (heart trace) a CT scan of the body and potentially an MRI scan of the brain and a bone scan (depending upon where the breast cancer is known to have spread to) as well as blood tests to determine if participants are suitable for the study.

During the study participants will receive daily palbociclib tablets and intravenous infusions of avelumab every two weeks. Participants will be monitored with regular blood tests and repeat CT scans every 8 weeks. At whatever time point the treatment stops working, the patient will stop treatment and will be asked to have further blood tests one month later as well as a check up with the study doctor.

In Part B of the study, patients with triple negative histology and positive androgen receptor status tested at the Royal Marsden will be required to have a cancer biopsy before participants start treatment on the study. LIke in Part A, participants will also have an ECG (heart trace)a CT scan of the body and potentially an MRI scan of the brain and a bone scan (depending upon where the breast cancer is known to have spread to) as well as blood tests to determine if participants are suitable for the study. During the study participants will receive daily palbociclib tablets and intravenous infusions of avelumab every two weeks. Participants will be monitored with regular blood tests and check-ups with the study doctor and repeat CT scans every 8 weeks as well as additional blood tests for research. After 3 weeks of treatment, the patient may have a further tumour biopsy, which is optional. At whatever timepoint the treatment stops working, the patient will stop treatment and will be asked to have further blood tests and a further biopsy. Participants will also have a check-up with the study doctor and blood tests one month later.

A maximum of 45 breast cancer patients will be enrolled; up to 18 patients in part A and 27 patients with AR+ triple negative breast cancer in part B.

This is a two-part phase 1b trial of induction palbociclib with the addition of avelumab. In Part A of the study, the MTD of the study will be determined using a 3+3 design. There will be a 1-week interval between the first and second patients started at each dose level.

In Part B, the MTD dose level will be expanded.

PAveMenT: Palbociclib and Avelumab in Metastatic AR+ Triple Negative Breast Cancer

PAveMenT: Phase Ib Study of Palbociclib and Avelumab in Metastatic AR+ Triple Negative Breast Cancer

There is not a plan to make IPD available.

Objective response rate in PAM50 luminal tumours compared to PAM50 non-luminal tumours

Objective response rate in PDL-1 positive compared to PDL-1 negative tumours

Objective response rate in high mutational load tumours compared to low mutational load tumours

Objective response rate in high TILs tumours compared to low TILs tumours at baseline and at D15

Exploratory assessment of ctDNA suppression as a potential biomarker of response. Described as the proportion of patients with any suppression among the patients with the best overall response of CR or PR and the non-responders SD or PD patients the 95% CI will be reported as appropriate.

Exploratory assessment of tumour reactive PBMC changes between baseline, D15 and D43.

Exploratory assessment of dynamic changes in T-cell clonality and T-cell receptor clonality between baseline and D15 and disease progression

Exploratory assessment of biomarkers of response in baseline tumour biopsy, and of acquired resistance in progression biopsies and plasma DNA.

Define MTD of palbociclib delivered in combination with avelumab

Response rate assessed by RECIST 1.1 by local radiology review

Clinical benefit rate (response or stable disease lasting at least 24 weeks), assessed by RECIST 1.1 by local radiology review.

Progression-free survival, calculated from day 1 of study treatment to the date of radiological disease progression or death from any cause.

Overall safety and tolerability of palbociclib with avelumab. Toxicity will be assessed by CTCAE (version 5) every 4 weeks during study treatment. Adverse events, including serious adverse events, will be recorded until 30 days after the last dose of study treatment with palbociclib or avelumab.

Overall survival, calculated from day 1 of study treatment to the date of death from any cause.

Breast Cancer Now

Royal Marsden NHS Foundation Trust

Testicular Neoplasms

Neoplasms, Germ Cell and Embryonal

Germ Cells Tumors

Cisplatin

Patients will receive pazopanib at the dose of 800 mg/day orally until disease progression or evidence of unacceptable toxicity/side effects. The study will be performed according to Simon's two-stage optimal design.

Pazopanib

This is an open label, single arm, single center, phase 2 study with the use of the antiangiogenic multikinase inhibitor pazopanib in a population of patients with germ cell tumors who are not cured following first or subsequent chemotherapy lines for metastatic disease, followed by eventual surgery.

Pazopanib in Advanced and Cisplatin-resistant Germ Cell Tumors

Phase II Study of Single-agent Pazopanib (Votrient®) for Patients With Relapsed or Refractory Germ-cell Tumors (GCT).

To evaluate the proportion of patients who are progression-free after 3 months of pazopanib.

A response rate will be considered as the sum of complete (CR) and partial responses (PR) according to the response evaluation criteria in solid tumors (RECIST), version 1.1

OS time will be calculated as the interval from treatment start date to the date of death for any cause, with censoring at the date of last contact for patients alive. The Kaplan-Meier method will be used to estimate the OS curve.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pilot Evaluation of 124I-Iodo-Azomycin Galacto-Pyranoside (*IAZGP) Positron Emission Tomography (PET) in the Imaging of Hypoxic Tumors	NCT00588276	Cervical Cancer HEENT Cancer Renal Cancer Uterine Cancer CERVIX UTERI NO... RECTUM	124I-Iodo-Azomy...	18 Years -	Memorial Sloan Kettering Cancer Center
PF-03446962 in Relapsed or Refractory Urothelial Cancer	NCT01620970	Transitional Ce...	PF03446962	18 Years -	Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
PF-03446962 in Relapsed or Refractory Urothelial Cancer	NCT01620970	Transitional Ce...	PF03446962	18 Years -	Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Phase II Study of Axitinib (AG-013736) With Evaluation of the VEGF-Pathway in Metastatic, Recurrent or Primary Unresectable Adrenocortical Cancer	NCT01255137	Adrenal Cortex ...	Axitinib	18 Years - 80 Years	National Institutes of Health Clinical Center (CC)
PAveMenT: Palbociclib and Avelumab in Metastatic AR+ Triple Negative Breast Cancer	NCT04360941	Triple Negative... Locally Advance... Recurrent Breas... Metastatic Brea... ER+ Breast Canc... HER2-positive B...	Palbociclib Avelumab	18 Years -	Royal Marsden NHS Foundation Trust
Pazopanib in Advanced and Cisplatin-resistant Germ Cell Tumors	NCT01743482	Germ Cell Tumor... Measurable Dise...	Pazopanib	18 Years - 75 Years	Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Spots Global Cancer Trial Database for measurable disease