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

NCT03496519 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: 17-1852.cc
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Solid Tumor, Adult

Keywords

Durvalumab; Trabectedin; Maximum Tolerated Dose; Lung Cancer; Sarcoma

Outcome Measures

Primary Outcomes (2)

• Recommended Dosage of the Durvalumab and Trabectedin Combination

  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.

  Up to 1 year on study treatment plus 90 days safety follow-up, up to 15 months

• Maximum tolerated dose

  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

  First 2 cycles at 21 days each, equal to 42 days.

Secondary Outcomes (7)

• Overall Response Rate (ORR) of the Durvalumab and Trabectedin Combination in the whole treated population and at the RP2D in the expansion cohort(s)

  After 2 cycles of study drugs to study end date, up to 24 months.

• Duration of Response (DOR) of the Durvalumab and Trabectedin Combination

  After 2 cycles of study drugs, up to 24 months.

• Clinical Benefit Rate (CBR) of the Durvalumab and Trabectedin Combination

  After 2 cycles of study drugs to study end date, up to 24 months.

• One Year Progression Free Survival (PFS) of the Durvalumab and Trabectedin Combination

  Study start date to progression, or death, whichever comes first, up to 24 months.

• One Year Overall Survival (OS) of the Durvalumab and Trabectedin Combination

  Study start date to death from any cause, up to 24 months.

Study Arms (2)

Dose Escalation

EXPERIMENTAL

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

Drug: Dose Escalation of Durvalumab and Trabectedin

Dose Expansion

EXPERIMENTAL

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.

Drug: Dose Expansion of Durvalumab and Trabectedin

Interventions

Dose Escalation of Durvalumab and Trabectedin DRUG

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

Also known as: Combination of Durvalumab and Trabectedin

Dose Escalation

Dose Expansion of Durvalumab and Trabectedin DRUG

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.

Also known as: Combination of Durvalumab and Trabectedin

Dose Expansion

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to understand and the willingness to sign a written informed consent document
• Written informed consent and any locally-required authorization (e.g., HIPAA in the USA) obtained from the patient prior to performing any protocol-related procedures, including screening evaluations
• AGE ≥ 18
• Alkaline phosphatase (ALP) level ≤ upper limit of normal (ULN)
• Aspartate aminotransferase (AST) and alanine amino transferase (ALT) ≤ ULN
• Bilirubin ≤ ULN, if total bilirubin is \> ULN, measure direct/indirect bilirubin to evaluate for Gilbert's Syndrome (if direct bilirubin is within normal range, subject may be eligible)
• Albumin ≥ 2.5 g/dL
• CPK ≤ 2.5 xULN
• Body weight \> 30 kg
• ECOG performance status 0-1
• Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
• Women \<50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
• Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \>1 year ago, had chemotherapy-induced menopause with last menses \>1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
• Evaluable disease for dose escalation, measurable disease per RECIST 1.1 for dose expansions
• Hemoglobin ≥ 9 g/dL

You may not qualify if:

• For the expansion cohort of NSCLC patients previously treated with and having progressed on immunotherapy patients must have no standard of care option available or have contraindications to such treatment (including those who decline such treatment).
• Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and exams including follow up.
• Strong inhibitors or inducers of cytochrome P450 3A (washout from prior use of such agents before C1D1 must exceed 21 days).
• Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
• Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies or other investigational product) ≤ 28 days. However, if a therapy has a short half-life, then patients may participate if they received prior treatment ≤ 28 days before starting study treatment with approval from the PI and AstraZeneca/Janssen. Acceptable washout periods include:
• days for prior TKI depending on half-life
• days for prior PD-1 or PD-L1 inhibitor treatment depending on the frequency of administration (i.e., wait one full cycle of prior PD-1 axis inhibition before starting study drugs)
• Therapeutic radiation within 6 weeks of cycle 1 day 1. Exceptions are palliative radiation and/or stereotactic radiation to non-target lesions.
• If received prior immunotherapy must not have experienced one of the following:
• A toxicity that led to permanent discontinuation of prior immunotherapy
• All AEs while receiving prior immunotherapy must have completely resolved or resolved to baseline prior to screening for this study.
• Must not have experienced a ≥Grade 3 immune related AE or an immune related neurologic or ocular AE of any grade while receiving prior immunotherapy. NOTE: Patients with endocrine AE of ≤Grade 2 are permitted to enroll if they are stably maintained on appropriate replacement therapy and are asymptomatic.
• Must not have required the use of additional immunosuppression other than corticosteroids for the management of an AE and must not have experienced recurrence of an AE if re-challenged.
• Prior treatment with trabectedin or trabectedin analog
• History of another malignancy except for:

Sponsors & Collaborators

• University of Colorado, Denver: lead

MeSH Terms

Conditions

Lung Neoplasms; Sarcoma

Interventions

Trabectedin

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Dioxoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrahydroisoquinolines; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Jose Pacheco

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2018
• First Posted: April 12, 2018
• Study Start: October 1, 2018
• Primary Completion: October 31, 2021
• Study Completion: October 31, 2021
• Last Updated: October 9, 2018

Record last verified: 2018-10