A phase II trIal for combination therapy with durvaLumab anD tremelimumAb in patients with metastatic solid tumors

Phase 1

• Conditions: Metastatic colorectal adenocarcinoma (without microsatellite instability (not MSI)), triple negative breast cancer, prostate adenocarcinoma, stomach and esophageal gastric junction adenocarcinoma and human papilloma virus (HPV) negative head and neck squamous cell carcinoma with detection of = 5 somatic mutations per megabase measured by whole exome sequencing in a tumor sample of the patient; MedDRA version: 20.0 Level: PT Classification code 10052360 Term: Colorectal adenocarcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0 Level: PT Classification code 10075566 Term: Triple negative breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0 Level: LLT Classification code 10066350 Term: Adenocarcinoma of the gastrooesophageal junction System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0 Level: PT Classification code 10060121 Term: Squamous cell carcinoma of head and neck System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0 Level: PT Classification code 10060862 Term: Prostate cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-003115-21-FR
• Lead Sponsor: Gustave Roussy

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-02-01
• Last Update Posted: 30 April 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 108

Inclusion Criteria

1.Written informed consent obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
2.Age = 18 years
3.Histologically confirmed diagnosis of metastatic colorectal adenocarcinoma (without microsatellite instability (not MSI), triple negative breast cancer, prostate adenocarcinoma, stomach and esophageal gastric junction adenocarcinoma and human papilloma virus (HPV) negative head and neck squamous cell carcinoma.
4.No standard treatment available or standard treatment refused
5.Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 with no deterioration over the 2 weeks prior to starting dose
6.Estimated life expectancy of greater than 12 weeks
7.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)
8.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
9.Haemoglobin > 9 g/dL, neutrophils > 1500/mm3, platelets > 100,000/mm3
10.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.
11.At least one lesion, not previously irradiated, that may 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.
12.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.
a.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)
b.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: Depo-Provera, Normal and low dose combined oral contraceptive pil, Norelgestromin/ethin

Exclusion Criteria

3.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.
4.Previous exposure to anti oncogenic vaccines, such as Sipuleucel – T is not allowed
5.History of another primary malignancy except for:
a.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
b.Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
c.Adequately treated carcinoma in situ without evidence of disease eg, cervical cancer in situ.
6.Receipt of the last dose of anti-cancer therapy 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.
7.Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab.
8.Any unresolved toxicity NCI CTCAE Grade =2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
a.Patients with Grade =2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
b.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.
9.Any concurrent chemotherapy, IMP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (eg, hormone replacement therapy) is acceptable.
10.Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IMP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
11.Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]).
12.History of primary immunodeficiency
13.History of allogeneic organ transplant
14.Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
15.Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease
16.Active infection including tuberculosis, hepatitis B , hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibo

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified