Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Tremelimumab

* Dose escalation will occur using a standard 3+3 dose escalation approach, beginning in dose level I with dose cohorts and rules for escalation and de-escalation.
* Tremelimumab-Fixed doses of Tremelimumab are given once per cycle
* MEDI3617-MEDI3617 is administered twice per cycle

MEDI3617

Patrick Ott, MD

This is an open label, phase I trial, testing the combination of Tremelimumab and MEDI3617 in patients with metastatic melanoma.

Description Patients who fulfill eligibility criteria will be entered into the trial to receive tremelimumab and MEDI3617.

After the screening procedures confirm participation in the research study:

The participant will be given a study drug-dosing calendar for each treatment cycle. The investigators are looking for the highest dose of the combination of study drugs that can be administered safely without severe or unmanageable side effects in participants that have melanoma, not everyone who participates in this research study will receive the same dose of the study drug. The dose given will depend on the number of participants who have been enrolled in the study prior and how well the dose was tolerated.

* Tremelimumab
* MEDI3617

Phase I Clinical Trial of Tremelimumab Plus MEDI3617 in Patients With Unresectable Stage III or Stage IV Melanoma

Determination of the maximum tolerated dose (MTD) of the combination of tremelimumab and MEDI3617

MedImmune LLC

F. Stephen Hodi, MD

Sponsor-Investigator

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Symptoms and General Pathology

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Recurrence

Glioma

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Ovarian Cancer

Ovarian Epithelial Cancer

Paclitaxel

Carboplatin

Bevacizumab

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Participants will receive MEDI3617 via intravenous (IV) infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days.

Participants will receive MEDI3617 with bevacizumab via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days.

Participants will receive MEDI3617 with bevacizumab via IV infusion every 2 weeks (Q2W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 28 days.

Participants will receive MEDI3617 on Days 1 and 15 with paclitaxel on Days 1, 8, and 15 via IV infusion in each cycle until unacceptable toxicity, documented disease progression, or other reasons. Each cycle consists of 28 days.

Participants will receive MEDI3617 with carboplatin and paclitaxel on Day 1 via IV infusion in each cycle until unacceptable toxicity, documentation of disease progression, or other reasons. Each cycle consists of 21 days.

Participants will receive MEDI3617 via IV infusion in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons.

Participants will receive bevacizumab via IV infusion in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons.

Participants will receive paclitaxel via IV infusion in each cycle until unacceptable toxicity, documented disease progression, or other reasons.

Participants will receive carboplatin via IV infusion in each cycle until unacceptable toxicity, documentation of disease progression, or other reasons.

MedImmune, LLC

To determine the maximum tolerated dose or optimal biological dose, and the safety profile of MEDI3617 when given as a single-agent or in combination with other chemotherapeutic agents in subjects with advanced solid malignancies resistant to standard therapy.

A Study to Evaluate the Safety and Antitumor Activity in Subjects With Advanced Solid Tumors

Phase 1/1b, Open-Label, Dose-Escalation and Expansion Study to Evaluate the Safety and Antitumor Activity of MEDI3617 as a Single-Agent or in Combination Therapy in Adult Subjects With Advanced Solid Tumors

DLT was defined as any treatment-related, grade 3 or higher toxicity (according to the National Cancer Institute's Common Terminology Criteria for Adverse Events \[NCI CTCAE\] version 4.0); occurring during the first 21 or 28 days after the initial administration of MEDI3617.

The dose-escalation phase used a 3 + 3 design. If greater than or equal to 2 (≥ 2) participants in a dose cohort experienced a DLT during the DLT period, the MTD was exceeded and no further participants were enrolled into that dose cohort. If this occurred, the preceding dose cohort was evaluated for the MTD and a total of 6 participants were treated at the preceding dose. If less than or equal to 1 (≤ 1) of 6 participants experienced a DLT at the preceding dose, then this dose level was the MTD. DLTs were defined as any treatment-related, grade 3 or higher toxicity (according to the National Cancer Institute's Common Terminology Criteria for Adverse Events \[NCI CTCAE\] version 4.0); occurring during the first 21 or 28 days after the initial administration of MEDI3617.

An adverse event (AE) was any untoward medical occurrence in a participant administered investigational product and which does not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) was an AE resulting in any of following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs were events occurring after administration of investigational product.

Laboratory evaluations were performed, including hematology and serum chemistry. An AE was any untoward medical occurrence in a participant administered investigational product and which does not necessarily have a causal relationship with this treatment. AEs related to laboratory abnormalities were recorded and reported.

Vital signs included parameters such as heart rate, blood pressure, temperature, weight and respiratory rate. An AE was any untoward medical occurrence in a participant administered investigational product and which does not necessarily have a causal relationship with this treatment. AEs related to vital signs abnormalities were recorded and reported.

An AE was any untoward medical occurrence in a participant administered investigational product and which does not necessarily have a causal relationship with this treatment. AEs related to echocardiogram abnormalities were recorded and reported. The only AE reported was ejection fraction decreased in the MEDI3617 + Paclitaxel total group.

An AE was any untoward medical occurrence in a participant administered investigational product and which does not necessarily have a causal relationship with this treatment. AEs related to electrocardiogram abnormalities were recorded and reported. The only AE reported was electrocardiogram QT prolonged in the MEDI3617 + Bevacizumab Q2W total group.

KPS scale: 100 is no evidence of disease; 90 is able to carry on normal activity, minor symptoms of disease; 80 is normal activity with effort, some symptoms of disease; 70 is cares for self; unable to do active work; 60 is requires occasional assistance, but is able to care for most of his needs; 50 is requires considerable assistance with frequent medical care; 40 is disabled, requires special care; 30 is severely disabled, hospitalization is indicated although death is not imminent; 20 is very sick, hospitalization necessary, active support treatment necessary; 10 is moribund, fatal processes progressing rapidly, 0 is dead.

Cmax is the maximum observed serum concentration of MEDI3617. Here, "n" is number of participants analyzed for this endpoint at a specific dose.

AUC0-last is the Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration of MEDI3617. Here, "n" is number of participants analyzed for this endpoint at a specific dose.

The AUC0-inf is the Area Under the Concentration-Time Curve From Time Zero to infinity of MEDI3617. Here, "n" is number of participants analyzed for this endpoint at a specific dose.

Systemic clearance describes the removal of drug from a volume of serum in a given unit of time (drug loss from the body). It is measured as milliliter per day (mL/day). Here, "n" is number of participants analyzed for this endpoint at a specific dose.

The t1/2 is the time in days required for the concentration of the drug to reach half of its original value. Here, "n" is number of participants analyzed for this endpoint at a specific dose.

The immunogenic potential of MEDI3617 was assessed by summarizing the number and percentage of participants who develop detectable ADA. Immunogenicity assessment included determination of anti-drug (MEDI3617) antibodies in serum samples. Samples were measured for the presence of ADA using validated immunoassays.

Objective response rate defined as the number of participants with confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR was defined as disappearance of all target lesions, any pathological lymph nodes must have reduction in short axis to less than (\<) 10 millimeter (the sum may not be "0" if there are target nodes). PR was defined as at least a 30 percent (%) decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Time to response (TTR) is defined as the time from the study entry to the first documentation of confirmed CR or confirmed PR. CR was defined as disappearance of all target lesions, any pathological lymph nodes must have reduction in short axis to less than (\<) 10 millimeter (the sum may not be "0" if there are target nodes). PR was defined as at least a 30 percent (%) decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Analysis was based on responses confirmed at a repeat assessment made at least 4 weeks after the initial response, with the TTR taken as the first time the response was observed, not the confirmation assessment. TTR was evaluated using the Kaplan-Meier method.

Duration of response is defined as the duration from the first documentation of objective disease response (ie, confirmed CR or confirmed PR) to the first documented disease progression. The duration of response was censored on the date of last tumor assessment documenting absence of disease progression for participants who have no documented progression prior to data cutoff, dropout, or the initiation of alternate anticancer treatment. Duration of response was evaluated for the subgroup of participants with an objective response using the Kaplan-Meier method.

Time to progression (TTP) is defined as time from the start of treatment with MEDI3617 until the documentation of disease progression. The TTP was censored on the date of last tumor assessment documenting absence of tumor progression for participants who have no documented progression prior to data cutoff, dropout, or the initiation of alternate anticancer treatment. Participants having no tumor assessments after the start of treatment with MEDI3617 had TTP censored on the first date of treatment with MEDI3617. TTP was evaluated using the Kaplan-Meier method.

PFS was measured from the start of treatment with MEDI3617 until the documentation of disease progression or death due to any cause, whichever occurred first. PFS was censored on the date of last tumor assessment documenting absence of tumor progression for participants who have no documented progression and were still alive prior to data cutoff, dropout, or the initiation of alternate anticancer treatment. Participants having no tumor assessments after the start of treatment with MEDI3617 had PFS censored on the first date of treatment with MEDI3617. PFS was evaluated using the Kaplan-Meier method.

Overall survival is defined as the time from the start of treatment with MEDI3617 until death. For the participants who were alive at the end of study or lost to follow-up, overall survival was censored on the last date when participants were known to be alive. Overall survival was evaluated using the Kaplan-Meier method.

Profile of Ang2 post MEDI3617 administration in relation to time course of antibody concentrations.

Participants received MEDI3617 via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days.

MEDI3617 SINGLE AGENT TOTAL

Participants received MEDI3617 with bevacizumab via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days.

MEDI3617 + BEVACIZUMAB Q3W ESCALATION TOTAL

Participants received MEDI3617 with bevacizumab via IV infusion every 2 weeks (Q2W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 28 days.

MEDI3617 + BEVACIZUMAB Q2W TOTAL

Participants received MEDI3617 on Days 1 and 15 with paclitaxel on Days 1, 8, and 15 via IV infusion in each cycle until unacceptable toxicity, documented disease progression, or other reasons. Each cycle consists of 28 days.

MEDI3617 + PACLITAXEL TOTAL

Participants received MEDI3617 with carboplatin and paclitaxel on Day 1 via IV infusion in each cycle until unacceptable toxicity, documentation of disease progression, or other reasons. Each cycle consists of 21 days.

MEDI3617 + CARBOPLATIN/PACLITAXEL TOTAL

Total

Age, Continuous

Sex: Female, Male

Safety population included all participants who receive any treatment with MEDI3617.

Mohammed Dar, MD

DLT Evaluable population included all participants enrolled in dose-escalation, who received at least 1 full assigned dose of single-agent MEDI3617 or full assigned doses of MEDI3617 and standard therapeutic agents on Cycle 1 and completed safety follow-up or experienced a DLT at any point during the 21-day or 28-day DLT evaluation period.

Number of Participants With Dose Limiting Toxicities (DLTs)

Maximum Tolerated Dose (MTD)

TEAEs

TESAEs

Safety population included all participants who received treatment with MEDI3617.

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)

Hematology: Anemia

Hematology: Leukopenia

Hematology: Neutropenia

Hematology: Thombocytopenia

Hematology: White blood cell count decreased

SerChem: Alanine aminotransferase increased

SerChem: Aspartate aminotransferase increased

SerChem: Blood alkaline phosphatase increased

SerChem: Blood creatinine increased

SerChem: Blood lactate dehydrogenase increased

SerChem: Blood potassium increased

SerChem: Blood triglycerides increased

SerChem: Blood urea increased

SerChem: Gamma-glutamyltransferase increased

SerChem: Hyperglycaemia

SerChem: Hyperkalaemia

SerChem: Hypertriglyceridaemia

SerChem: Hyperuricaemia

SerChem: Hypoalbuminaemia

SerChem: Hypocalcaemia

SerChem: Hypoglycaemia

SerChem: Hypokalaemia

SerChem: Hypomagnesaemia

SerChem: Hyponatremia

Number of Participants With Laboratory Abnormalities Recorded as Adverse Events (AEs)

Arrhythmia

Sinus tachycardia

Tachycardia

Pyrexia

Weight decreased

Weight increased

Hypertension

Hypotension

Number of Participants With Vital Sign Abnormalities Recorded as Adverse Events (AEs)

Number of Participants With Echocardiogram Abnormalities Recorded as Adverse Events (AEs)

Safety population included all participants who received treatment with MEDI3617

Number of Participants With Electrocardiogram Abnormalities Recorded as Adverse Events (AEs)

Cohort -2 (n=3)

Cohort -1 (n=2)

Cohort 1 (n=6)

Cohort 2 (n=3)

Cohort 3 (n=3)

Cohort 4 (n=3)

Cohort 5 (n=4)

Cohort ovarian cancer expansion (OCE) -1 (n=15)

Cohort OCE 1 (n=2)

Cohort MB 1A (n=4)

Cohort MB 2A (n=3)

Cohort MB 3A (n=3)

Cohort MB 4A (n=6)

Cohort MB 1B (n=7)

Cohort MB 2B (n=3)

Cohort MB 3B (n=8)

Cohort MB 4B (n=8)

Cohort TT2A (n=9)

Cohort MP1 (n=7)

Cohort MP2 (n=6)

Cohort MCP1 (n=4)

Cohort MCP2 (n=3)

All participants who received treatment with MEDI3617 and for whom PK blood samples were collected and evaluated.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase I Clinical Trial of Tremelimumab Plus MEDI3617 in Patients With Unresectable Stage III or Stage IV Melanoma	NCT02141542	Metastatic Mela...	Tremelimumab MEDI3617	18 Years -	Dana-Farber Cancer Institute
A Study to Evaluate the Safety and Antitumor Activity in Subjects With Advanced Solid Tumors	NCT01248949	Advanced Solid ... Advanced Recurr...	MEDI3617 Bevacizumab Paclitaxel Carboplatin	18 Years - 99 Years	MedImmune LLC
A Study to Evaluate the Safety and Antitumor Activity in Subjects With Advanced Solid Tumors	NCT01248949	Advanced Solid ... Advanced Recurr...	MEDI3617 Bevacizumab Paclitaxel Carboplatin	18 Years - 99 Years	MedImmune LLC

Spots Global Cancer Trial Database for medi3617

Every month we try and update this database with for medi3617 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for medi3617

Every month we try and update this database with for medi3617 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for medi3617 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.