Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Sarcoma

Lung Neoplasms

Soft Tissue Sarcoma

Antineoplastic Agents

All Drugs and Chemicals

Durvalumab

Trabectedin

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Antineoplastic Agents, Immunological

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Dose escalation will occur following a 3+3 design in all advanced tumor types meeting the inclusion and exclusion criteria.

* Cohort -1 (if necessary): Durvalumab 1125mg with Trabectedin 0.5mg/m2
* Cohort 1: Durvalumab 1125mg with Trabectedin 0.75mg/m2
* Cohort 2: Durvalumab 1125mg with Trabectedin 1.0mg/m2
* Cohort 3: Durvalumab 1125mg with Trabectedin 1.2mg/m2
* Cohort 4: Durvalumab 1125mg with Trabectedin 1.5mg/m2

Patients at this level will receive the safest dose of Durvalumab and Trabectedin that was determined during the Dose Escalation Phase. There will be a fixed dosage of Durvalumab, 1125mg, given intravenously over 60 minutes on Day 2 every 21 days. There will be fixed dosage of Trabectedin for each cohort, given through intravenous infusion as an outpatient, over a 24 hour period on Day 1 every 21 days.

There will be a fixed dosage of Durvalumab, 1125mg, given intravenously over 60 minutes on Day 2 every 21 days. There will be an increase in Trabectedin for each cohort, given through intravenous infusion over a 24 hour period on Day 1 every 21 days as an outpatient.

* Cohort -1: Durvalumab 1125mg with Trabectedin 0.5mg/m2
* Cohort 1: Durvalumab 1125mg with Trabectedin 0.75mg/m2
* Cohort 2: Durvalumab 1125mg with Trabectedin 1.0mg/m2
* Cohort 3: Durvalumab 1125mg with Trabectedin 1.2mg/m2
* Cohort 4: Durvalumab 1125mg with Trabectedin 1.5mg/m2

Dose Escalation of Durvalumab and Trabectedin

There will be a fixed dosage of Durvalumab, 1125mg, given intravenously over 60 minutes on Day 2 every 21 days. There will be a fixed dosage of Trabectedin for each cohort, whatever was determined to be the safest dose during the Dose Escalation Phase, and it will be given through intravenous infusion over a 24 hour period on Day 1 every 21 days as an outpatient.

Dose Expansion of Durvalumab and Trabectedin

Jose Pacheco

A phase 1 study examining the combination of Durvalumab (MEDI4736) and Trabectedin in various solid tumor types. The study seeks to determine a safe dose of the combination of study drugs and then examine this dose in larger groups of patients of specific tumor types to evaluate its anti-tumor efficacy. Treatment will continue in patients who respond for up to 1 year.

This study will include dose escalation and dose expansion phases.

In the dose escalation portion, patients with advanced cancer will be enrolled and treated with Durvalumab and Trabectedin. Durvalumab will be administered at the same dose in each dose escalation cohort, while the dose of Trabectedin will be progressively increased in different cohorts until the safest dose of the combination is determined.

In the dose expansion portion patients will be treated with the safest dose of the study drugs determined during the dose escalation phase. There will be two separate groups of patients treated at this dose to evaluate anti-tumor efficacy of the combination. One group will consist of non-small-cell lung cancer patients previously treated with PD-1 or PD-L1 inhibitors and another group will consist of an immunotherapy naive group of patients. This immunotherapy naive group of patients will include sarcoma and another tumor type, this other tumor type will be determined based on anti-tumor efficacy seen during the dose escalation.

The study drugs will be given intravenously every 3 weeks. Treatment will continue for up to one year or until disease progression.

Assessing the Combination of Durvalumab (MEDI4736) and Trabectedin in Solid Tumors

A Phase I Study Assessing the Combination of Durvalumab (MEDI4736) and Trabectedin in Solid Tumors

Recommended Phase II Dose (RP2D) is the dose determined safest for further evaluation based on both early and late onset side effects detected during the dose escalation phase.

Maximum Tolerated Dose (MTD) is defined as the highest dose level with no more than 1 Dose Limiting Toxicity (DLT) reported out of up to 6 DLT-evaluable subjects determined during the dose escalation phase

ORR is determined by RECIST v1.1 and iRECIST response criteria.

The time period for which a partial response (PR) or complete response (CR) is maintained.

Determined by complete response, partial response, or stable disease.

PFS is determined by RECIST v1.1 and iRECIST

Determined continuously throughout the study.

Number of participants with abnormal laboratory values and/or adverse events that are related to treatment.

Spots Global Cancer Trial Database for dose expansion of durvalumab and trabectedin