Basket Trial for Combination Therapy With Durvalumab (Anti-PDL1) (MEDI4736) and Tremelimumab (Anti-CTLA4) in Patients With Metastatic Solid Tumors

NCT03982173 | Withdrawn Phase 2

• 2 other identifiers: 2018-003115-212018/2798
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

To determine the efficacy (as measured by overall tumour response rate) of the combination of durvalumab and tremelimumab when given to previously treated patients with solid tumors harboring a high mutational load.

Conditions

Metastatic Colorectal Cancer; Triple Negative Breast Cancer; Prostate Adenocarcinoma; Stomach Adenocarcinoma; Esophageal Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Objective tumour response rate

  measured according to RECIST (version 1.1)

  at 12 weeks

Study Arms (1)

previously treated patients with solid tumors

EXPERIMENTAL

previously treated patients with solid tumors harboring a high mutational load.

Drug: Tremelimumab; Drug: Durvalumab

Interventions

Tremelimumab DRUG

tremelimumab 75mg

previously treated patients with solid tumors

Durvalumab DRUG

Durvalumab 1500mg

previously treated patients with solid tumors

Eligibility Criteria

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

You may qualify if:

• Written informed consent obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
• Age ≥ 18 years
• Histologically confirmed diagnosis of metastatic colorectal adenocarcinoma (without microsatellite instability (not MSI), triple negative breast cancer, prostate adenocarcinoma and stomach and esophageal gastric junction adenocarcinoma.
• Metastatic disease or unresectable locally advanced malignancy that is resistant or refractory to standard therapy or for which standard therapy does not exist or is not considered appropriate by the Investigator
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 with no deterioration over the 2 weeks prior to starting dose
• Estimated life expectancy of greater than 12 weeks
• Detection of ≥ 5 somatic mutations per megabase measured by whole exome sequencing in a tumor sample of the patient taken after completing last therapy, within a molecular screening program (this data must been known before screening period)
• Total bilirubin ≤ 1.5 ULN (for subjects with documented/suspected Gilbert's disease, bilirubin ≤ 3 ×ULN), ALT or AST ≤ 2.5 ULN (for subjects with liver metastases, AST or ALT ≤ 5 × ULN), albumin ≥ 30 g/L
• Haemoglobin \> 9 g/dL, neutrophils \> 1500/mm3, platelets \> 100,000/mm3
• Serum creatinine CL\>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance.
• At least one lesion, not previously irradiated, which can be measured at baseline as ≥10 mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and suitable for repeated assessment according to Response Evaluation Criteria in Solid Tumors (RECIST) guidelines v1.1.
• Females of childbearing potential who are sexually active with a non-sterilized male partner must use at least 1 highly effective method of contraception, from screening, and must agree to continue using such precautions for 180 days after the final dose of durvalumab and tremelimumab or 90 days after the last dose of durvalumab monotherapy, whichever is the longer time period; cessation of birth control after this point should be discussed with a responsible physician. Male partners of a female subject must use male condom plus spermicide throughout this period. Not engaging in sexual activity for the total duration of the drug treatment and the drug washout period is an acceptable practice; however, periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control.
• Females of childbearing potential are defined as those who are not surgically sterile (ie, bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or postmenopausal (defined as 12 months with no menses without an alternative medical cause)
• Subjects must use at least one method of contraception highly effective, such as Copper T intrauterine device, Levonorgestrel-releasing intrauterine system (eg, Mirena® ) a Etonogestrel implants; eg, Implanon or Norplan, Intravaginal device; eg, ethinylestradiol and etonogestrel, Medroxyprogesterone injection: DepoProvera, Normal and low dose combined oral contraceptive pil, Norelgestromin/ethinylestradiol transdermal system or use of Cerazette (desogestrel)
• Female subjects should also refrain from breastfeeding throughout this period

You may not qualify if:

• Participation in another clinical study with an investigational product during the last 4 weeks (excepting noninterventional clinical studies)
• Concurrent enrolment in another clinical study (with an investigational product), unless it is an non-interventional clinical study
• Any previous treatment with immunotherapy including (but not limited to) compounds such as, PD1 or PD-L1 inhibitors, including durvalumab or an anti-CTLA4 inhibitors, including tremelimumab.
• Previous exposure to anti oncogenic vaccines, such as Sipuleucel - T is not allowed
• History of another primary malignancy except for:
• Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of study drug and of low potential risk for recurrence
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
• Adequately treated carcinoma in situ without evidence of disease eg, cervical cancer in situ.
• Receipt of the last dose of anti-cancer therapy (chemotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) 28 days prior to the first dose of study drug. A shorter duration of five half times may be considered after Sponsor approval, for patients treated with non-cytotoxic drugs). (If sufficient wash-out time has not occurred due to the schedule or PK properties of an agent, a longer wash-out period may be required.)
• Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab. The following are exceptions to this criterion:
• Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra articular injection)
• Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
• Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication)
• Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
• Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the Study Physician.

Sponsors & Collaborators

• Gustave Roussy, Cancer Campus, Grand Paris: lead

MeSH Terms

Conditions

Colorectal Neoplasms; Triple Negative Breast Neoplasms; Adenocarcinoma Of Esophagus

Interventions

tremelimumab; durvalumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Breast Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2019
• First Posted: June 11, 2019
• Study Start: September 1, 2020
• Primary Completion: September 1, 2024
• Study Completion: December 5, 2024
• Last Updated: January 26, 2023

Record last verified: 2023-01