E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cancer of the ovary, cervix, endometrium, bladder, prostate (castration-resistant prostate cancer [CRPC]), head and neck (squamous cell carcinoma of the head and neck [SCCHN]), esophagus or lung (non-small cell lung cancer [NSCLC] |
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E.1.1.1 | Medical condition in easily understood language |
Cancers of the ovary, cervix, endometrium, bladder, prostate, head and neck, esophagus or lung |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10014742 |
E.1.2 | Term | Endometrial neoplasms malignant |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10060862 |
E.1.2 | Term | Prostate cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10008342 |
E.1.2 | Term | Cervix carcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10062878 |
E.1.2 | Term | Gastrooesophageal cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10023774 |
E.1.2 | Term | Large cell lung cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10005003 |
E.1.2 | Term | Bladder cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10029104 |
E.1.2 | Term | Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10033128 |
E.1.2 | Term | Ovarian cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067821 |
E.1.2 | Term | Head and neck cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To establish the tolerability of HuMax®-TF-ADC in a mixed population of patients with specified solid tumors |
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E.2.2 | Secondary objectives of the trial |
To establish the long term tolerability of HuMax®-TF-ADC in a mixed population of patients with specified solid tumors.
To determine the maximum tolerated dose (MTD) and the recommended dose for phase II trials with HuMax®-TF-ADC .
To establish the pharmacokinetic (PK) profile of HuMax®-TF-ADC after single and multiple infusions.
To evaluate the anti-tumor activity of HuMax®-TF-ADC in a mixed population of patients with specified solid tumors. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients with relapsed, advanced and/or metastatic cancer who have failed available standard treatments or who are not candidates for standard therapy.
Age ≥ 18 years.
Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Life expectancy of at least three months.
A negative serum pregnancy test (if female and aged between 18-55 years old).
Women who are pregnant or breast feeding are not to be included.
Patients, both females and males, of reproductive potential must agree to use adequate contraception during and for six months after the last infusion of HuMax®-TF-ADC.
Following receipt of verbal and written information about the study, patients must provide signed informed consent before any study-related activity is carried out.
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E.4 | Principal exclusion criteria |
Known past or current coagulation defects leading to increased risk of bleeding.
Ongoing major bleeding
A baseline QT interval as corrected by Fridericia’s formula (QTcF) > 450 msec, a complete left bundle branch block (defined as a QRS interval ≥ 120 msec in left bundle branch block form) or an incomplete left bundle branch block.
Have received granulocyte colony stimulating factor (G-CSF) or granulocyte/macrophage colony stimulating factor support within one week or pegylated G-CSF within two weeks before the Screening Visit.
Have received a cumulative dose of corticosteroid ≥ 150 mg (prednisone or equivalent doses of corticosteroids) within two weeks before the first infusion.
Major surgery within six weeks or open biopsy within 7 days before drug infusion.
Plan for any major surgery during treatment period.
Any history of intracerebral arteriovenous malformation, cerebral aneurysm, brain metastases or stroke.
Any anticancer therapy including; small molecules, immunotherapy, chemotherapy monoclonal antibodies or any other experimental drug within five half lives before first infusion (for anti-cancer therapies with half-lives > 8 days, a washout period of at least 40 days is acceptable).
Prior treatment with bevacizumab within twelve weeks before the first infusion.
Radiotherapy within 28 days prior to first dose.
Patients who have not recovered from symptomatic side effects of radiotherapy at the time of initiation of screening procedure.
Known past or current malignancy other than inclusion diagnosis, except for:
- Cervical carcinoma of Stage 1B or less.
- Non-invasive basal cell or squamous cell skin carcinoma.
- Non-invasive, superficial bladder cancer.
- Prostate cancer with a current PSA level < 0.1 ng/mL.
- Breast cancer in BRCA1 or BRCA2 positive ovarian cancer patients.
- Any curable cancer with a complete response (CR) of > 5 years duration.
Known human immunodeficiency virus seropositivity.
Positive serology for hepatitis C based on test at screening.
Inflammatory bowel disease including Crohn’s disease and colitis ulcerosa.
Inflammatory lung disease including moderate and severe asthma and chronic obstructive pulmonary disease (COPD) requiring chronic medical therapy.
Ongoing acute or chronic inflammatory skin disease.
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E.5 End points |
E.5.1 | Primary end point(s) |
AEs during the study: incidences of AEs, SAEs, infusion-related AEs, CTCAE grade ≥ 3 AEs, and AEs related to study drug. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Safety laboratory parameters (hematology, biochemistry, coagulation factors and flow cytometry).
- Skin disorders.
- Bleeding events.
- Neuropathy.
- PK parameters (clearance, volume of distribution and area-under-the-concentration-time curve [AUC0 Clast and AUC0-∞]), maximum concentration [Cmax], time of Cmax [Tmax], pre-dose values, and half life of HuMax®-TF-ADC and free toxin [MMAE]).
- Immunogenicity of HuMax®-TF-ADC (anti-drug antibodies).
- Anti-tumor activity measured by tumor shrinkage (based on computerized tomography [CT] scan evaluations), change in PSA and CA 125.
- Objective Response (CR or Partial Response [PR]), Disease Control (CR, PR or Stable Disease [SD]), after 6, 12, 24 and 36 weeks, Progression-Free Survival (PFS) and Duration of Response (DoR).
Exploratory Endpoints:
- TF expression in tumor biopsies
- Circulating TF
- Protein biomarker
- Circulating cell-free deoxyribonucleic acid (cfDNA)) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At end of trial and as part of preparations for subsequent trials, exploratory analysis of subsets of data may be performed. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 12 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 23 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Denmark |
Sweden |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 28 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 13 |