Symptoms and General Pathology

All Conditions

Neoplasms

Nervous System Diseases

Rare Diseases

Recurrence

Glioblastoma

Brain Neoplasms

Disease Progression

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Doxorubicin

Liposomal doxorubicin

Immunomodulating Agents

Antibodies, Bispecific

Immunoglobulins

Mitogens

Panitumumab

EGFR(V)-EDV-Dox administered via 20 minute intravenous infusion once a week for seven weeks (1 Cycle). Subjects will receive one of two dose levels: 5 x 10\^9 or 8 x 10\^9. All subjects will undergo an adapted dose escalation regime in the first cycle of treatment. For subsequent cycles all doses will be administered at full strength (5x10\^9 or 8x10\^9 EGFR(V)-EDV-Dox). Subjects may receive further cycles of treatment if the tumor remains stable or is responding, and/or they are deriving clinical benefit from the therapy and are tolerating treatment.

EGFR(V)-EDV-Dox using EnGeneIC EDV™ technology is a bacterially derived minicell which packages a toxic payload, Doxorubicin, into a 400 nm particle which targets specific cancer cells using bispecific antibodies (BsAb). BsAb-targeted, payload-packaged EDV nanocells only exit the leaky blood vessels associated with tumors and enter into the tumor microenvironment. The BsAb binds to the tumor cell-surface receptor, where the EDV is taken up, broken down within the cancer cell and releases the Doxorubicin. The residual EDVs that do not make it into the tumor microenvironment, are engulfed by cells of the immune system and since the EDVs are derived from bacteria, they carry potent immuno-stimulating components which appear to bypass the immuno-suppression caused by the tumor.

EGFR(V)-EDV-Dox

Kelly Szajna, RN BSN

Whitney Webb, RN MSN CNRN

Tamika Wong, MPH

John A Boockvar, MD

Jennifer MacDiarmid, Ph.D

Himanshu Brahmbhatt, Ph. D

Gary L Gallia, M.D., Ph.D

Stuart A Grossman, M.D.

The purpose of the Cerebral EDV study is to determine the safety and tolerability of EGFR(V)-EDV-Dox in order to establish the best dose level to be used in future studies. The study will also examine the body's immune response to EGFR(V)-EDV-Dox and assess if it is effective in the treatment of patients with recurrent glioblastoma multiforme (GBM).

This is an open-label, Phase 1, dose exploration and preliminary immunogenicity study of single agent EGFR(V)-EDV-Dox in subjects with recurrent glioblastoma (GBM). Eligible subjects enrolled in the study will receive EGFR(V)-EDV-Dox administered weekly for 7 weeks via IV 20 minute infusion, followed by radiological evaluation at week 8 (1 Cycle). Subjects may continue to receive subsequent cycles of EGFR(V)-EDV-Dox unless the subject becomes intolerant to investigational product (IP), withdraw consent or the individual is no longer receiving clinical benefit (factors taken in to consideration will be disease progression radiologically or clinically, and clinical benefits to quality of life). Tumour assessment will be repeated after each 7 week cycle (week 8).

The study will take place in two parts, Part 1 (Dose Exploration) and Part 2 (Dose Expansion).

Part 1 - Dose Exploration will assess the safety and tolerability of multiple doses of drug at two dose levels (5 x 10\^9 and 8 x 10\^9) and will enroll prior to Part 2. Three subjects will be recruited per dose level. Enrollment will begin with the 5 x 10\^9 dose level, and the decision to enroll to the 8 x 10\^9 dose level will follow a comprehensive safety evaluation and a standard 3 + 3 dose escalation study design.

Part 2 - Dose Expansion will be conducted pending safety results of Part 1 to provide guidance regarding the recommended phase 2 dose (RP2D). Subjects will be treated and assessed as outlined in Part 1 above. If 0 out of 3 subjects, or 1 out of 6 subjects, experience dose limiting toxicities (DLTs) at the 5 x 10\^9 dose level in Part 1, additional subjects to a total of 10 will be recruited to this dose level in Part 2. Similarly, if 0 out of 3 subjects, or 1 out of 6 subjects, experience DLTs at the 8 x 10\^9 dose level in Part 1, additional subjects to a total of 10 will be recruited to this dose level in Part 2. If both dose levels are tolerated, a total of 10 subjects per dose level will be enrolled.

A safety follow-up visit must be performed 30 (+5) days after the last dose of drug for all subjects.All subjects who discontinue investigational product and who have not withdrawn full consent to participate in the study will continue in the long term follow-up phase. Long term follow-up will continue approximately every 1 month for 12 months, from the 30 (+5) day follow-up visit, then approximately every 2-3 months for the extent of subject survival.

A Study to Evaluate the Safety, Tolerability and Immunogenicity of EGFR(V)-EDV-Dox in Subjects With Recurrent Glioblastoma Multiforme (GBM)

A Phase 1 Study to Evaluate the Safety, Tolerability, and Immunogenicity of EGFR (Vectibix® Sequence)-Targeted EnGeneIC Dream Vectors Containing Doxorubicin (EGFR(V)-EDV-Dox) in Subjects With Recurrent Glioblastoma Multiforme (GBM)

Recording of adverse Events (AE's) and clinically significant changes in vital signs, physical and neurological examinations, cardiac tests, radiological imaging inc. CT scan (Day 27/28) and clinical laboratory tests.

Disease response will be measured by Magnetic Resonance Imaging (MRI) using Response Assessment in Neuro-Oncology (RANO).

Review of safety data for dose limiting toxicity (DLT) evaluable subjects.

Johns Hopkins University

Engeneic Pty Limited

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Carcinoma

Carcinoma, Renal Cell

Adenocarcinoma

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

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Anti-Infective Agents

Amino Acids

Sirolimus

Erlotinib Hydrochloride

Temsirolimus

MTOR Inhibitors

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Clotrimazole

Miconazole

Antifungal Agents

Immunosuppressive Agents

Immunologic Factors

Tyrosine

Erlotinib hydrochloride (Tarceva) will be self-administered in an open-label unblinded manner to all patients enrolled in the study. During the treatment period, patients will receive single-agent Tarceva, 150 mg/day.

Sirolimus (Rapamune) will be self-administered in an open-label unblinded manner to all patients enrolled in the study. Patients will receive a loading dose of 6 mg of Rapamune seven days after beginning treatment with Tarceva™ followed by a dose of 2mg/day.

Patients will receive single-agent Tarceva, 150 mg/day

Erlotinib hydrochloride

Patients will receive a loading dose of 6 mg of Rapamune seven days after beginning treatment with Tarceva™ followed by a dose of 2mg/day.

Thomas W Flaig, MD

The purpose of this study is to test the safety and efficacy of the combination of erlotinib hydrochloride (Tarceva™) and sirolimus (Rapamune™) in the treatment of patients with metastatic kidney cancer.

Despite recent advances metastatic renal cell carcinoma remains an incurable condition. Currently available treatment with high-dose interleukin-2 can lead to complete responses in a small minority of selected patients but is markedly toxic and not broadly available. FDA-approved multikinase inhibitors (sorafenib and sunitinib malate) often cause partial and transient tumor regression. There is no standard treatment metastatic renal cell carcinoma for patients whose disease progressed on multikinase inhibitors. The kinase mammalian target of rapamycin (mTOR) is overstimulated in a subset of renal cell carcinomas and other malignancies and can be blocked by sirolimus leading to growth arrest. Erlotinib hydrochloride is a drug that blocks the function of the epidermal growth factor receptor (EGFR), often over expressed in kidney cancer. Sirolimus and EGFR inhibitors and been safely used in combination. In vitro experiments show that erlotinib enhances the sirolimus induced growth impairment in a panel of renal cell carcinoma cells. In the present study patients with metastatic renal cell carcinoma whose disease progressed on multikinase inhibitors will be treated with the combination of erlotinib hydrochloride (Tarceva™) and sirolimus (Rapamune™). This is a single arm trial with no placebo or drug-based control arm

Erlotinib and Sirolimus for the Treatment of Metastatic Renal Cell Carcinoma

A Phase II Single Arm Clinical Trial to Evaluate the Efficacy and Safety of the Combination of Tarceva™ (Erlotinib Hydrochloride) and Rapamune™ (Sirolimus) in the Treatment of Metastatic Renal Cell Carcinoma.

Time to progression was defined as the time from beginning of therapy until disease progression or death. For subjects who had not progressed at the time of statistical analysis, progression-free survival was censored at the date of their last tumor assessment. Kaplan-Meier method was used to estimate median progression-free survival. Progression was defined as radiographic progression according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria (year 2000 version), non-compliance in obtaining scans, unequivocal clinical progression or the initiation of another medication for the treatment of renal cell carcinoma.

For all subjects who had not died at the time of statistical analysis, duration of survival will was censored at the date of last contact. Kaplan-Meier methodology was used to estimate the magnitude of the treatment effect as described for progression-free survival.

Genentech, Inc.

University of Colorado, Denver

Monitoring included patient interview, physical exam, routine laboratory tests (even in absence of symptoms) and appropriate work-up of any new symptoms or laboratorial abnormalities.

Erlotinib (Tarceva) therapy was started at 150 mg by mouth daily from day 1 to be taken at least 1 hour before or 2 hours after a meal. Sirolimus was initiated on day 8 (D8) with a loading dose of 6mg by mouth, followed by a daily dose of 2mg by mouth, on the basis of the product prescribing information for low-to-moderate immunologic risk renal transplant patients.

Erlotinib and Sirolimus

Age, Continuous

Age, Categorical

Sex: Female, Male

Race (NIH/OMB)

Ethnicity (NIH/OMB)

United States

Region of Enrollment

It was calculated that 25 participants will provide 80% power to detect an improvement in progression-free survival from 12 to 24 weeks in a pretreated population of renal cell carcinoma patients.

One limitation of this study was the lack of von Hippel-Lindau (VHL) mutational status assessment.

Dr. Thomas Flaig

Per protocol analysis was used and 25 participants that were enrolled in the study were included in the analysis.

Progression-free Survival

Overall Survival

Overall Study

Skin and Connective Tissue Diseases

Behaviors and Mental Disorders

Exanthema

Skin Diseases

Quality of Life

Micronutrients

Provitamins

Vitamins

Trace Elements

Apply at least two times a day on face, chest and upper arms during the 6 week treatment period

dexpanthenol 5% cream

Cetomacrogol cream

Christine Boers-Doets, MSc

Mario Lacouture, MD

Johan Nortier, PhD

Objective:

To assess the preemptive effect of Bepanthen® on decreasing the incidence of specific ≥ grade 2 dermatological side effects of interest in respect of compliance to EGFRI agents, HRQoL and the adherence during the 6-week skin treatment period. The adherence to the study creams will also be studied.

Rationale:

Dermatological side effects, such as papulopustular eruption, xerosis, pruritus, periungual inflammation, mucosal-, and hair abnormalities, and edema occur in up to 90% of patients during treatment with epidermal growth factor receptor inhibitors (EGFRI). Patients are hindered in their daily activities and cannot maintain privacy about their illness because of the prominent side effects. The aesthetic discomfort, which is frequently associated with itching or painful skin or nails can lead to a decreased health related quality of life (HRQoL) and to dose reduction or discontinuation of anticancer treatment.

Patients with dermatological side effects have also an increased risk for cutaneous infections (at least 38%) which can complicate dermatological side effects.

At present, evidence of the effectiveness of the management options for dermatological side effects is lacking, and the effect of the dermatological side effects on HRQoL and adherence remains poorly understood.

Dexpanthenol cream (Bepanthen®, Bayer) has been used extensively to ameliorate acute radiation induced skin toxicity, diaper dermatitis, irritant hand dermatitis, graft-donor site wound healing and burn patients. The hypothesis is that its skin healing possibilities decreases this kind of side effects.

Study design:

Multicenter, two-arm randomized, double blind, prospective parallel group design, phase III study

Study population:

Each patient starting for the first time with EGFRI anticancer therapy which can cause papulopustular eruption (cetuximab, panitumumab, erlotinib, gefitinib, lapatinib, or other), will be included.

Intervention:

80 patients will receive for the first 6 weeks of treatment Bepanthen cream, 80 patients Cetomacrogol cream to apply twice daily. Using FACT-EGFRI, a dermatology-specific questionnaire, this study examines the effect of these side effects on three domains of HRQoL - symptoms, emotions, and functioning. Severity of dermatological side effects will be assessed using the NCI-CTCAE v4.0. Correlation of dermatology HRQoL scores with NCI-CTCAE grade, sex, age, type of EGFRI, and cancer type will be conducted.

Bepanthen Versus Cetomacrogol in Epidermal Growth Factor Receptor Inhibitors (EGFRI)

Phase III Randomized Double-Blind Trial of Bepanthen® Cream Versus Cetomacrogol Cream in the Prevention of Papulopustular Eruption in Patients Receiving Epidermal Growth Factor Receptor Inhibitors (EGFRI): BeCet

The incidence of grade ≥ 2 papulopustular eruption during the 6 week skin treatment within Bepanthen and Cetomacrogol, as measured by the CTCAE v4.0 and DERETT-H, an dermatologic specific healthcare provider questionnaire for Dermatological Reactions Targeted Therapy.

Assess the impact of papulopustular eruptions on HRQoL as measured by the Functional Assessment of Cancer Therapy Questionnaire - EGFRI (FACT-EGFRI) and newly developed symptom experience diary Dermatological Reactions Targeted Therapy - Patients (DERETT-P).

Determine the patient tolerability and satisfaction of Bepanthen®/ Cetomacrogol cream as measured by DERETT-P.

Determine the effectiveness of Bepanthen® cream versus Cetomacrogol cream on the adherence to anticancer agents as measured by FACT-EGFRI and DERETT-P.

Assessments during the 6-week skin treatment period of the incidence and time to onset of other dermatological side effects which can appear together with papulopustular eruptions as measured by DERETT-H.

CB Boers ORG

Memorial Sloan Kettering Cancer Center

Leiden University Medical Center

Bayer

Impaqtt Foundation

Respiratory Tract (Lung and Bronchial) Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Pruritus

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Skin Manifestations

Antiemetics

Gastrointestinal Agents

Anti-Allergic Agents

Dermatologic Agents

Aprepitant

Desloratadine

Loratadine

Fosaprepitant

Neurokinin-1 Receptor Antagonists

Substance P

Neurokinin A

Neurotransmitter Agents

Cholinergic Antagonists

Cholinergic Agents

Histamine H1 Antagonists

Histamine

Histamine phosphate

Histamine H1 Antagonists, Non-Sedating

Histamine Antagonists

aprepitant 125mg d1, 80mg d3 and d5, along with placebo 5mg d1-d28;

placebo 125mg d1, 80mg d3 and d5, along with desloratadine 5mg d1-d28

aprepitant 125mg d1, 80mg d3 and d5; until pruritus recurrence or discontinuation of EGFR-TKI or safely issues (SAE etc.)

Desloratadine 5mg d1-d28; until pruritus recurrence or discontinuation of EGFR-TKI or safely issues (SAE etc.)

Placebo of aprepitant 125mg d1, 80mg d3 and d5; until pruritus recurrence or discontinuation of EGFR-TKI or safely issues (SAE etc.)

Placebo of aprepitant

Placebo of desloratadine 5mg d1-d28; until pruritus recurrence or discontinuation of EGFR-TKI or safely issues (SAE etc.)

Placebo of desloratadine

Li Zhang, professor

Study hypothesis is that aprepitant is more effective than desloratadine in relieving pruritus caused by EGFR TKIs. Primary endpoint is the effective rate of pruritus, effective treatment defined as visual analogue scale (VAS) decrease ≥ 50% after treatment compared to baseline score. 130 NSCLC patients undertaken EGFR-TKI and suffer from moderate or severe pruritus (VAS score ≥ 4) will be enrolled in this study, and stratified (gender, VAS 4-6 or 7-10, and 2nd generation TKI or non 2nd generation) randomized (1:1) into aprepitant or desloratadine treatment. VAS investigation will be taken once a week to treatment end (4 weeks).

This is a prospective, randomized control, double-blinded, phase II clinical trial. Study hypothesis is that aprepitant is more effective than desloratadine in relieving pruritus caused by EGFR TKIs. Primary endpoint is the effective rate of pruritus, effective treatment defined as visual analogue scale (VAS) decrease ≥ 50% after treatment (1 week) compared to baseline score. The VAS inquiry will be taken once a week for 4 weeks. Quality of life investigation will be performed at baseline, 1 week and 4 weeks after treatment using SKINDEX-16 questionnaire. 130 NSCLC patients undertaken EGFR-TKI and suffer from moderate or severe pruritus (VAS score ≥ 4) will be enrolled in this study, and stratified (gender,and VAS 4-6 or 7-10, and 2nd generation TKI or non 2nd generation) randomized (1:1) into aprepitant or desloratadine treatment. Aprepitant arm will be administrated aprepitant 125mg d1, 80mg d3 and d5, along with placebo 5mg d1-d28; desloratadine arm will be administrated placebo 125mg d1, 80mg d3 and d5, along with desloratadine 5mg d1-d28. Tolerance evaluation will be taken according to National Cancer Institute (NCI)-Common Terminology Criteria (CTC) For Adverse Events (AE) V4.03.

Aprepitant vs. Desloratadine in EGFR-TKIs Related Pruritus Treatment

Aprepitant vs. Desloratadine in Non-small Cell Lung Cancer Patients With Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors Related Pruritus: A Prospective, Randomized Control, Double-blinded, Phase II Clinical Trial

effective treatment of pruritus relieving defined as visual analogue scale (VAS) decrease ≥ 50% after treatment compared to baseline score

the time from pruritus effective relief to VAS score increase ≥ baseline level, the VAS inquiry will be taken once a week.

using SKINDEX-16 questionnaire to assess patients quality of life

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study to Evaluate the Safety, Tolerability and Immunogenicity of EGFR(V)-EDV-Dox in Subjects With Recurrent Glioblastoma Multiforme (GBM)	NCT02766699	Glioblastoma Astrocytoma, Gr...	EGFR(V)-EDV-Dox	18 Years -	Engeneic Pty Limited
Erlotinib and Sirolimus for the Treatment of Metastatic Renal Cell Carcinoma	NCT00353301	Renal Cell Carc...	Erlotinib hydro... Sirolimus	18 Years -	University of Colorado, Denver
Bepanthen Versus Cetomacrogol in Epidermal Growth Factor Receptor Inhibitors (EGFRI)	NCT01136005	Cancer Skin Rash	dexpanthenol 5%... Cetomacrogol cr...	18 Years -	Impaqtt Foundation
Aprepitant vs. Desloratadine in EGFR-TKIs Related Pruritus Treatment	NCT02646020	Non-small Cell ...	Aprepitant Desloratadine Placebo of apre... Placebo of desl...	18 Years -	Sun Yat-sen University
Erlotinib and Sirolimus for the Treatment of Metastatic Renal Cell Carcinoma	NCT00353301	Renal Cell Carc...	Erlotinib hydro... Sirolimus	18 Years -	University of Colorado, Denver
A Study to Evaluate the Safety, Tolerability and Immunogenicity of EGFR(V)-EDV-Dox in Subjects With Recurrent Glioblastoma Multiforme (GBM)	NCT02766699	Glioblastoma Astrocytoma, Gr...	EGFR(V)-EDV-Dox	18 Years -	Engeneic Pty Limited
Erlotinib and Sirolimus for the Treatment of Metastatic Renal Cell Carcinoma	NCT00353301	Renal Cell Carc...	Erlotinib hydro... Sirolimus	18 Years -	University of Colorado, Denver

Spots Global Cancer Trial Database for receptor, epidermal growth factor