Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Digestive System Diseases

Rare Diseases

Carcinoma

Glioblastoma

Carcinoma, Renal Cell

Carcinoma, Hepatocellular

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Adenocarcinoma

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Bevacizumab

Temozolomide

Axitinib

Sunitinib

Crizotinib

Sorafenib

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine Kinase Inhibitors

Tyrosine

Histological or cytological diagnosis of advanced/metastatic solid tumor that is resistant to standard therapy or for which no standard therapy is available.

Patients with histologically confirmed metastatic renal cell cancer with no prior systemic therapy directed at the malignant tumor.

Patients with histologically confirmed metastatic renal cell cancer whose prior systemic therapy directed at the malignant tumor was single agent VEGF inhibitor and who now have acquired resistance to this treatment.

Patients with histologically confirmed glioblastoma whose disease has failed on previous therapy, and which must have included treatment with external beam radiation and temozolomide chemotherapy, and who now have radiographically recurrent or progressive disease.

Patients with histologically confirmed advanced-stage (unresectable or metastatic) hepatocellular carcinoma who have not received previous systemic therapy directed at the malignant tumor will be eligible to receive crizotinib plus sorafenib, should this combination be tested.

Three combinations will be prioritized, namely crizotinib plus axitinib, crizotinib plus sunitinib and crizotinib plus bevacizumab, with a fourth combination, crizotinib plus sorafenib to be tested only if crizotinib does not combine with either axitinib and/or sunitinib. All study drugs are tablets or capsules except for bevacizumab which is parenteral (intravenous). Dosage, frequency and duration to be determined.

Crizotinib plus VEGF inhibitor combinations

Study drugs are tablets or capsules; dosage, frequency and duration to be determined.

Crizotinib plus axitinib

Crizotinib plus sunitinib

Study drugs are tablets or capsules except for bevacizumab which is parenteral (intravenous). Dosage, frequency and duration to be determined.

Crizotinib plus bevacizumab

Crizotinib plus sorafenib

Pfizer CT.gov Call Center

Despite the success of anti-angiogenic therapy in multiple treatment settings, a fraction of patients are refractory to vascular endothelial growth factor (VEGF) inhibitor treatment while the majority of patients will eventually develop evasive resistance and exhibit disease progression while on therapy. It is proposed that mesenchymal-epithelial transition factor (c-MET) and its ligand hepatocyte growth factor (HGF or scatter factor) contribute significantly to VEGF inhibitor resistance such that combining a c-MET inhibitor with a VEGF inhibitor will provide additional clinical activity compared to VEGF inhibitor alone. This hypothesis will be tested using the cMET/ALK inhibitor, crizotinib, in combination with individual VEGF inhibitors. Three combinations will be prioritized, namely crizotinib plus axitinib, crizotinib plus sunitinib and crizotinib plus bevacizumab, with a fourth combination, crizotinib plus sorafenib to be tested only if crizotinib does not combine with either axitinib and/or sunitinib.

A Study Of Crizotinib Plus VEGF Inhibitor Combinations In Patients With Advanced Solid Tumors.

A Phase 1B, Open-Label, Dose Escalation Study To Evaluate Safety, Pharmacokinetics And Pharmacodynamics Of Crizotinib (PF-02341066) Plus VEGF Inhibitor Combinations In Patients With Advanced Solid Tumors.

Pfizer

Skin and Connective Tissue Diseases

Melanoma

Neuroendocrine Tumors

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Antibodies

Antibodies, Monoclonal

Lenvatinib

Pembrolizumab

Immunomodulating Agents

Immunoglobulins

Mitogens

Immune Checkpoint Inhibitors

Neoadjuvant pembrolizumab \& lenvatinib for 6 weeks followed by definitive surgery then adjuvant pembrolizumab alone for 46 weeks

Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.

Lenvatinib is an oral potent multiple RTK inhibitor that selectively inhibits VEGF receptors, VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4), fibroblast growth factor receptor (FGFR1-4), platelet derived growth factor (PDGFRα), stem cell factor receptor (KIT), and rearranged during transfection (RET)

Georgina Long, MBBS, PhD

Maria Gonzalez

In many cancers, early stage diagnosis and early treatment offers the best chance of a prolonged recurrence free- and overall survival. Neoadjuvant immunotherapy involves administering immune checkpoint inhibitors before surgical resection in high-risk resectable disease, such as mucosal melanoma. In resectable cancers, immune checkpoint inhibitors can enhance anti-tumour immunity by exploiting a competent immune system prior to surgery. Activating antigen-specific T cells found in the primary or baseline tumour continue to exert anti-tumour effects on remaining neoplastic cells after the resection of the original tumour, potentially preventing recurrences from occurring.

In resectable mucosal melanoma, an opportunity exists to improve clinical outcomes with the addition of neoadjuvant and adjuvant systemic therapy with nivolumab and lenvatinib as an adjunct to surgery.

Neoadjuvant Pembrolizumab and Lenvatinib for Mucosal Melanoma

A Multicentre, Open Label, Phase II Study to Determine the Response to Neoadjuvant Pembrolizumab and Lenvatinib Followed by Adjuvant Treatment With Pembrolizumab and Lenvatinib in Mucosal Melanoma

Proportion of patients with a complete metabolic resolution (complete resolution of 18F-FDG uptake within the tumour volume); partial metabolic response (reduction of a minimum of 30% in tumour SUV normalised by lean body mass \[SUL\]; stable metabolic response (neither CR, PR or PD) and progressive metabolic disease (an increase of 30% in tumour SUL peak or the appearance of new lesions) in the neoadjuvant period

Proportion of patients with a complete or partial immune related response; patients with no response and patients who have confirmed disease progression in the neoadjuvant period

Proportion of patients with either of: progression of disease prior to surgery or which precludes surgery, local or distant disease recurrence, mucosal melanoma related death and treatment related death, whichever occurs first from the first dose of neoadjuvant treatment or from surgery (disease recurrence).

Proportion of patients who are recurrence-free at yearly time points from the date of definitive surgery and from the end of adjuvant treatment until the end of 5 years from C1D1. To include time to any recurrence, new primary disease, locoregional recurrence and distant recurrence.

Proportion of patients alive at yearly time points from the date of first neoadjuvant study treatment (C1D1) until the end of 5 years follow up.

* Number, grade and duration of drug related adverse events across different grades, with attribution to pembrolizumab, lenvatinib or both.
* Number, grade and duration of drug related adverse events requiring an interruption or permanent discontinuation of pembrolizumab, lenvatinib or both.
* The completion rate of scheduled pembrolizumab, lenvatinib or both (administered doses / scheduled doses).

The rate of surgical complications during and following definitive surgery

The change in longitudinal quality of life individual and overall scores from baseline.

To correlate gastrointestinal mucosal integrity with bacterial composition in stool samples, clinical outcomes.

Concordance of pathological response with RECIST response, PERCIST response and immune-related response crtieria.

Tumour and immune cell expression of HIF1a and immune cell densities will be compared between baseline and day 8 melanoma tissue biopsies.

Proportion of patients with complete absence of residual melanoma cells in the the planned resected tumour site(s) at week 6 surgery

Proportion of patients with a complete or partial RECIST response; patients with no RECIST response and patients who have RECIST confirmed disease progression in the neoadjuvant period.

Merck Sharp & Dohme LLC

Melanoma Institute Australia

Symptoms and General Pathology

Sarcoma

Disease Progression

Sarcoma, Alveolar Soft Part

Neoplasms, Connective and Soft Tissue

Soft Tissue Sarcoma

Oculocerebral Syndrome With Hypopigmentation

Alveolar Soft Part Sarcoma

Cediranib

Patients will be randomized to receive cediranib (30 mg) or sunitinib malate (37.5 mg) orally, once a day in 28-day cycles

At the time of disease progression, patients will cross over to the other treatment arm after a 2-week wash-out period

Cediranib, a small molecule inhibitor of VEGF receptor tyrosine kinases, is showing preliminary evidence of activity in patients with ASPS.

Sunitinib, a small molecule inhibitor of VEGF receptor tyrosine kinases, is showing preliminary evidence of activity in patients with ASPS.

Alice P Chen, M.D.

Background:

* Alveolar soft part sarcoma (ASPS) is a rare, highly vascular tumor accounting for less than 1% of soft tissue sarcomas. There is no effective systemic treatment for patients with metastatic ASPS. Little is known with regards to relevant molecular markers as potential therapeutic targets.
* Cediranib (AZD2171) and sunitinib (SU011248), oral small molecule inhibitors of VEGF receptor tyrosine kinases, are showing preliminary evidence of activity in patients with ASPS.

Objectives:

* Part I: Determine the objective response rate (ORR) of single-agent cediranib and single-agent sunitinib malate in patients with advanced ASPS.
* Part II: Determine the ORR of cediranib in patients who progress on the sunitinib arm, and determine the ORR of sunitinib in patients who progress on the cediranib arm.
* Determine the progression-free survival (PFS) at 24 weeks for single-agent cediranib and

single-agent sunitinib malate in patients with advanced ASPS.

Eligibility:

* Patients aged greater than or equal to 16 years with histologically or cytologically confirmed metastatic ASPS.
* Patients must show evidence of objective disease progression per RECIST 1 on scans within the 3-month period immediately preceding enrollment. Both scans used to determine disease progression should have been obtained within this 6-month period.
* Patients with newly diagnosed, unresectable, measurable, metastatic ASPS who show clinical evidence of disease progression will be eligible.
* Patients must not have received treatment with any VEGF receptor tyrosine kinase inhibitor (e.g., cediranib, sunitinib, pazopanib, sorafenib); however, prior treatment with bevacizumab is allowed.

Design:

* Part I: Patients will be randomized to receive cediranib (30 mg) or sunitinib malate (37.5 mg) orally, once a day in 28-day cycles.
* Part II: At the time of disease progression, patients will cross over to the other treatment arm after a 2-week wash-out period.
* Appropriate anatomic imaging studies will be performed at baseline and every 2 cycles for restaging.
* The study will be conducted using an optimal two-stage design to rule out an unacceptably low 15% clinical response rate (PR+CR) in favor of a modestly high response rate of 40%.

The study will initially enroll 10 evaluable patients in each arm. If 0 or 1 of the 10 patients has a clinical response, then no further patients will be accrued. If 2 or more the first 10 patients have a response, then accrual continues to a total of 22 patients in each arm.

Background:

* Alveolar soft part sarcoma (ASPS) is a rare, highly vascular tumor accounting for less than 1% of soft tissue sarcomas. There is no effective systemic treatment for patients with metastatic ASPS. Little is known with regards to relevant molecular markers as potential therapeutic targets.
* Cediranib (AZD2171) and sunitinib (SU011248), oral small molecule inhibitors of VEGF receptor tyrosine kinases, are showing preliminary evidence of activity in patients with ASPS.

Objectives:

* Part I: Determine the objective response rate (ORR) of single-agent cediranib and single-agent sunitinib malate in patients with advanced ASPS.
* Part II: Determine the ORR of cediranib in patients who progress on the sunitinib arm, and determine the ORR of sunitinib in patients who progress on the cediranib arm.
* Determine the progression-free survival (PFS) at 24 weeks for single-agent cediranib and

single-agent sunitinib malate in patients with advanced ASPS.

Eligibility:

Status Update: Patients enrolled after Amendment G (version dated 08/16/2013), will be

evaluated and compared to the first 13 patients by the study statistician and the Principal

Investigator. Patients with newly diagnosed ASPS with clinical evidence of disease progression will also be assessed separately.

* Patients aged greater than or equal to 16 years with histologically or cytologically confirmed metastatic ASPS.
* Patients must show evidence of objective disease progression per RECIST 1 on scans within the 3-month period immediately preceding enrollment. Both scans used to determine disease progression should have been obtained within this 6-month period.
* Patients with newly diagnosed, unresectable, measurable, metastatic ASPS who show clinical evidence of disease progression will be eligible.
* Patients must not have received treatment with any VEGF receptor tyrosine kinase inhibitor (e.g., cediranib, sunitinib, pazopanib, sorafenib); however, prior treatment with bevacizumab is allowed.

Design:

* Two sets of patients will be enrolled and assessed in separate cohorts: a) patients with non-newly diagnosed ASPS and b) patients with newly diagnosed ASPS
* Part I: Patients will be randomized to receive cediranib (30 mg) or sunitinib malate (37.5 mg) orally, once a day in 28-day cycles. As of May 6, 2019, we have closed the cediranib arm of the newly diagnosed ASPS cohort due to inadequate activity per the statistical plan; all newly diagnosed ASPS patients will be assigned to the sunitinib malate treatment arm.
* Part II: At the time of disease progression, patients will cross over to the other treatment arm after a 2-week wash-out period. As of May 6, 2019, patients in the newly diagnosed ASPS cohort are not eligible to cross over to the cediranib treatment arm, which was closed due to inadequate activity.
* Appropriate anatomic imaging studies will be performed at baseline and every 2 cycles for restaging.
* The study will be conducted using an optimal two-stage design to rule out an unacceptably low 15% clinical response rate (PR+CR) in favor of a modestly high response rate of 40%.

The study will initially enroll 10 evaluable patients in each arm. If 0 or 1 of the 10 patients has a clinical response, then no further patients will be accrued. If 2 or more the first 10 patients have a response, then accrual continues to a total of 22 patients in each arm.

Sunitinib or Cediranib for Alveolar Soft Part Sarcoma

A Phase II Trial In Which Patients With Metastatic Alveolar Soft Part Sarcoma Are Randomized to Either Sunitinib or Cediranib Monotherapy, With Cross-Over at Disease Progression

.All IPD recorded in the medical record will be shared with intramural investigators upon request.

Objective responses will be determined by RECIST criteria

National Cancer Institute (NCI)

Rectal Neoplasms

Colonic Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Micronutrients

Herbal and Botanical

Leucovorin

Fluorouracil

Oxaliplatin

Vatalanib

Cola

Novartis/Schering AG, Germany

The purpose of this study is to compare treatment with oxaliplatin/5-FU/leucovorin plus vatalanib versus oxaliplatin/5-FU/leucovorin plus placebo in patients with colorectal cancer that has spread to other organs and whose disease has worsened after treatment with irinotecan.

Study of Oxaliplatin/5-FU/Leucovorin Plus Vatalanib Versus Oxaliplatin/5-FU/Leucovorin in Patients With Previously Treated Metastatic Colorectal Cancer

A Randomized, Double-blind, Placebo-controlled, Phase III Study of Oxaliplatin/5-fluorouracil/Leucovorin With PTK787/ZK 222584 or Placebo in Patients With Previously Treated Metastatic Adenocarcinoma of the Colon or Rectum

Bayer

Novartis Pharmaceuticals

Novartis / Schering AG, Germany

To compare treatment with oxaliplatin/5-FU/leucovorin plus vatalanib versus oxaliplatin/5-FU/leucovorin plus placebo in patients with colorectal cancer that has spread to other organs and are seeking first chemotherapy treatment

Study of Oxaliplatin/5-FU/Leucovorin Plus Vatalanib Versus Oxaliplatin/5-FU/Leucovorin in Patients With Metastatic Colorectal Cancer.

A Randomized, Double-blind, Placebo-controlled, Phase Lll Study in Patients With Metastatic Adenocarcinoma of the Colon or Rectum Who Are Receiving First-line Chemotherapy With Oxaliplatin/5-fluorouracil/Leucovorin With PTK787/ZK 222584 or Placebo

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study Of Crizotinib Plus VEGF Inhibitor Combinations In Patients With Advanced Solid Tumors.	NCT01441388	Carcinoma, Rena... Glioblastoma Carcinoma, Hepa...	Crizotinib plus... Crizotinib plus... Crizotinib plus... Crizotinib plus... Crizotinib plus... Crizotinib plus... Crizotinib plus...	18 Years -	Pfizer
Neoadjuvant Pembrolizumab and Lenvatinib for Mucosal Melanoma	NCT05545969	Mucosal Melanom...	Pembrolizumab Lenvatinib	18 Years - 100 Years	Melanoma Institute Australia
Sunitinib or Cediranib for Alveolar Soft Part Sarcoma	NCT01391962	Sarcoma, Alveol...	Cediranib Sunitinib	16 Years - 120 Years	National Institutes of Health Clinical Center (CC)
Study of Oxaliplatin/5-FU/Leucovorin Plus Vatalanib Versus Oxaliplatin/5-FU/Leucovorin in Patients With Previously Treated Metastatic Colorectal Cancer	NCT00056446	Colorectal Neop... Colonic Neoplas... Rectal Neoplasm...	Vatalanib	18 Years -	Novartis
Sunitinib or Cediranib for Alveolar Soft Part Sarcoma	NCT01391962	Sarcoma, Alveol...	Cediranib Sunitinib	16 Years - 120 Years	National Institutes of Health Clinical Center (CC)
Study of Oxaliplatin/5-FU/Leucovorin Plus Vatalanib Versus Oxaliplatin/5-FU/Leucovorin in Patients With Metastatic Colorectal Cancer.	NCT00056459	Colorectal Neop... Colonic Neoplas... Rectal Neoplasm...	Vatalanib	18 Years -	Novartis

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