| Eligibility |
Inclusion criteria
1. Patients with histologically proven primary or recurrent desmoid tumor with currently
bi-dimensionally measurable tumor by WHO criteria.
2. Patients with disease that is either unresectable or for which the patient refuses
surgery but is currently progressing, as defined by:
- 20% increase in tumor volume within 6 months OR
- Recurrent disease within 1 year of surgery OR
- Desmoid related symptoms as documented by a PRO questionnaire and documentation
that symptoms are related to desmoid and not prior therapies.
3. Willingness to provide tumor biopsies prior to treatment and while on treatment
4. Patients may have been previously treated with local therapies such as surgery,
radiation, radiofrequency ablation, or cryosurgery provided this has been completed at
least 4 weeks prior to registration and recovered from therapy related toxicity to
less than CTCAE grade 2 and show no improvement in tumor size or symptom score.
5. Patients may have been treated with systemic therapies such as tyrosine kinase
inhibitors, hormone inhibitors or nonsteroidal anti-inflammatory drugs (NSAIDs)
provided this has been completed at least 4 weeks prior to registration and recovered
from any therapy related toxicity to less than CTCAE grade 2 and show no improvement
in tumor size or symptom score.
6. Patients may have been treated with systemic therapies such as cytotoxics, biologics
or other unclassified experimental therapies provided this has been completed at least
8 weeks prior to registration and recovered from any therapy related toxicity to less
than CTCAE grade 2 and show no improvement in tumor size or symptom score.
7. Patients who have been treated with immune therapies such as vaccines, dendritic or
other whole cell therapies, oncolytic or other viral approaches within the preceding
12 months should be discussed with the Medical Monitor prior to screening and
enrollment into the study to determine eligibility.
8. Age: 18 and over (no pre-pubertal patients)
9. ECOG Performance status: 0-1
10. Women of child-bearing potential (WOCBP) and men who are sexually active with WOCBP
must agree to use one highly effective method of contraception, including hormonal
contraceptives (e.g. combined oral contraceptives, patch, vaginal ring, injectables,
and implants); intrauterine device (IUD) or intrauterine system (IUS); vasectomy or
tubal ligation; and one effective method of contraception, including male condom,
female condom, cervical cap, diaphragm or contraceptive sponge or abstain from sex for
the duration of study participation and for 4 months following completion of BC2059
administration. Should a woman become pregnant or suspect she is pregnant while she or
her partner is participating in this study, she should inform her treating physician
immediately. See section 8.7.3 for more information.
Contraception includes:
- Total abstinence (when this is in line with the preferred and usual lifestyle of
the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal,
post-ovulation methods) and withdrawal are not acceptable methods of
contraception
- Female sterilization (have had surgical bilateral oophorectomy with or without
hysterectomy), total hysterectomy or tubal ligation at least 6 weeks before
taking study treatment. In case of oophorectomy alone, only when the reproductive
status of the woman has been confirmed by follow up hormone level assessment
- Male sterilization (at least 6 months prior to screening). For female patients on
the study the vasectomized male partner should be the sole partner for that
patient.
- Use of oral (estrogen and progesterone), injected or implanted combined hormonal
methods of contraception or placement of an intrauterine device (IUD) or
intrauterine system (IUS) or other forms of hormonal contraception that have
comparable efficacy (failure rate <1%), for example hormone vaginal ring or
transdermal hormone contraception.
- Sexually active males must use a condom during intercourse while taking drug and
for 4 months after stopping study treatment and should not father a child in this
period. A condom is required to be used also by vasectomized men in order to
prevent delivery of the drug via seminal fluid.
In case of use of oral contraception women should have been stable on the same pill
for a minimum of 3 months before taking study treatment.
Women are considered post-menopausal and not of child bearing potential if they have
had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile
(e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral
oophorectomy (with or without hysterectomy) or tubal ligation at least 6 weeks ago. In
the case of oophorectomy alone, only when the reproductive status of the woman has
been confirmed by follow up hormone level assessment is she considered not of child
bearing potential.
11. Hematopoietic:
- Absolute granulocyte count = 1,500/mm3
- Platelet count = 100,000/mm3
- Hemoglobin at least 10.0 g/dL (transfusion allowed, subjects that require
transfusion or growth factor need to demonstrate stable hemoglobin for at least 7
consecutive days of hemoglobin = 10 g/dL)
12. Hepatic:
- Bilirubin no greater than 1.5 times institutional upper limit of normal, in the
absence of documented Gilbert's syndrome
- Transaminases no greater than 3 times upper limit of normal (ULN)
- Alkaline phosphatase no greater than 3 times ULN
13. Renal: Creatinine clearance =75 mL/min by Cockcroft-Gault
14. Pulmonary:
- Diffusing capacity of the lung for carbon monoxide (DLCO) greater than 75%
predicted by single breath test
- Capillary oxygen saturation (O2 sat) > 95% by pulse oximetry
Exclusion Criteria
1. Patients who have not recovered to grade 1 from adverse events related to prior
therapy excluding those considered not clinically significant (ex. Lymphopenia).
2. History of allergic reactions attributed to compounds of similar chemical or biologic
composition to BC2059 or other agents used in study
3. Patients with metabolic bone disease (ex. Hyperparathyroidism, Paget's disease, or
osteomalacia)
4. Clinically significant, uncontrolled heart disease and/or cardiac repolarization
abnormality or QTc > 480 msec
5. Uncontrolled concurrent illness including, but not limited to: ongoing or active
infection (Viral, bacterial, fungal or other)
6. Psychiatric illness/social situations that would limit compliance with study
requirements
7. Pregnant and breastfeeding women are excluded from this study. The effects of BC2059
on the developing human fetus have the potential for teratogenic or abortifacient
effects. There is an unknown but potential risk for adverse events in nursing infants
secondary to treatment of the mother with BC2059.
8. HIV-positive patients on combination antiretroviral therapy are ineligible because of
the potential for pharmacokinetic interactions with BC2059
9. Patients with abnormal serum chemistry values other than the specific limits detailed
above, that in the opinion of the Investigator is considered to be clinically
significant, should be discussed with the Medical Monitor before being enrolled in the
study.
10. Lack of peripheral venous or central venous access or any condition that would
interfere with drug administration or collection of study samples
11. Personal history of malignancy except:
- Cervical intraepithelial neoplasia;
- Skin basal cell carcinoma;
- Treated localized prostate carcinoma with PSA <1 ng/mL;
- Neoplasia treated with curative intent, in remission for at least five years and
considered at low risk of relapse.
12. Patients with familial adenomatous polyposis.
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