Initiation of bisphosphonate/denosumab therapy during protocol treatment; patients on stable doses of bisphosphonates or denosumab which have been started no less than 4 weeks prior to treatment start may continue on this medication; NOTE: initiation of bisphosphonate/denosumab therapy will be allowed for the treatment of osteoporosis or prevention of skeletal-related events (SRE) during protocol treatment
Symptomatic hypercalcemia requiring continued use of bisphosphonate or denosumab therapy
Recent initiation of bone modifying therapy with a bisphosphonate or denosumab unless it has been started more than 4 weeks prior to the first dose of the study regimen; patients who are already enrolled in this study can initiate bone modifying therapy after the first set of re-staging scans (>= 8 weeks from cycle 1, day 1)
Bisphosphonate therapy (osteoporosis or symptomatic hypercalcaemia) or denosumab (osteoporosis) prior to study drug
COHORT 1: HORMONE RECEPTOR POSITIVE BREAST CANCER: Patients with bone metastases who have initiated denosumab or bisphosphonate therapy within 28 days prior to cycle 1 day 1
COHORT 2: TRIPLE NEGATIVE BREAST CANCER: Patients with bone metastases who have initiated denosumab or bisphosphonate therapy within 28 days prior to cycle 1 day 1
COHORT 3: ENDOMETRIAL CANCER: Patients with bone metastases who have initiated denosumab or bisphosphonate therapy within 28 days prior to cycle 1 day 1
Administration of other prior anticancer therapies within 4 weeks of enrollment, except ongoing administration of a bisphosphonate drug or denosumab as treatment for bone metastasis
Patients receiving bisphosphonate or denosumab therapy must have been on stable doses for at least 4 weeks prior to screening
Bisphosphonate or denosumab dosage must have been stable for at least 4 weeks before day 1 for patients receiving these therapies.
Uncontrolled hypercalcemia (> 1.5 mmol/L ionized calcium or calcium[Ca] > 12 mg/dL or corrected serum calcium > ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab\r\n* Subjects who are receiving bisphosphonate therapy or denosumab specifically to prevent skeletal events and who do not have a history of clinically significant hypercalcemia are eligible\r\n* Subjects who are receiving denosumab prior to enrollment must be willing and eligible to receive a bisphosphonate instead while in the study
The use of a RANKL inhibitor (denosumab) must be discontinued during the study; bisphosphonate therapy is permitted
Within 14 days before first dose of avelumab: therapeutic or palliative radiation therapy; (subjects receiving bisphosphonate or denosumab are eligible provided treatment was initiated at least 14 days before the first dose of avelumab)
Except GnRH analogue therapy, any other therapies for prostate cancer (excluding bisphosphonate and denosumab) must be discontinued 3 weeks before the first dose of study drugs
Initiating bisphosphonate or denosumab therapy or adjusting dose/regimen within 3 months prior to Cycle 1 Day 1. Subjects on a stable bisphosphonate or denosumab therapy are eligible and may continue.
TREATMENT: Patients with bone metastases or hypercalcemia on intravenous bisphosphonate treatment, denosumab, or similar agents are eligible to participate and may continue this treatment; patients with prostate cancer may continue LHRH agonists or antagonists
IV bisphosphonate and denosumab for bony metastatic disease will be allowed
Patient may have received or plan to receive concurrent bone targeting agents that do not have an effect on PSA (e.g. denosumab or bisphosphonate)
Participants receiving bisphosphonate or denosumab therapy must have been on a stable dose for at least 4 weeks
A minimum of 28 days beyond initiation of bisphosphonate or denosumab therapy
High levels of calcium requiring bisphosphonate therapy or denosumab.
Intravenous (IV) bisphosphonate and denosumab for bony metastatic disease will be allowed
Subjects must be on therapy with bisphosphonate and denosumab. and are required to have been on such therapy for at least 1 month before start of study treatment.
Treatment with bisphosphonate or denosumab within 12 weeks before randomisation.
Patients receiving bisphosphonate therapy or denosumab must have been on a stable dose for at least 4 weeks prior to enrollment
Participants must be at least 2 weeks out from prior chemotherapy, or other cancer-directed therapy (including novel agents), with adequate recovery of toxicity to baseline, or grade =< 1, with the exception of alopecia and hot flashes; washout from hormonal therapy and radiation is not required as long as participants have adequately recovered from any significant toxicities that occurred as a result from these treatments (grade 1 or less); participants may have initiated bisphosphonate/denosumab therapy prior to start of protocol therapy; bisphosphonate/denosumab therapy may continue during protocol treatment; such participants will have bone lesions considered evaluable for progression; washout for trastuzumab or pertuzumab is not necessary
Patients may not initiate bisphosphonate or denosumab therapy while receiving treatment on this study; patients who have begun receiving bisphosphonate or denosumab therapy prior to registration may continue at the same intervals used prior to study registration
Uncontrolled hypercalcemia ( ?1.5 mmol/L ionized calcium or Ca > 12 mg/dL) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab (patients receiving bisphosphonate therapy or denosumab to prevent skeletal events and who do not have a history of clinically significant hypercalcemia are eligible, though patients receiving denosumab must be willing and eligible to receive bisphosphonates instead)
Participants receiving bisphosphonate or denosumab therapy must be on stable doses for at least 4 weeks before start of study therapy
Subjects currently on a bisphosphonate or denosumab are eligible for study therapy
Lack of treatment with a bisphosphonate or denosumab
Lack of treatment with a bisphosphonate or denosumab
Initiation of bisphosphonate therapy < 4 weeks prior to first dose of KPT-330; patients receiving bisphosphonate or denosumab therapy must be on stable doses for at least 4 weeks prior to first dose of KPT-330
Lack of treatment with a bisphosphonate or denosumab
Lack of treatment with a bisphosphonate or denosumab
Subject receiving bisphosphonate or denosumab therapy must have been on stable doses for at least 4 weeks prior to Day 1
Participants on bisphosphonates/denosumab may continue receiving bisphosphonate therapy during study treatment
Symptomatic hypercalcemia requiring bisphosphonate or denosumab therapy
No prior history of bisphosphonate or denosumab use in the past 12 months
Previous treatment with denosumab or use of bisphosphonate within 3 months of start of study
Uncontrolled hypercalcemia (> 1.5 mmol/L ionized calcium or calcium > 12 mg/dL or corrected serum calcium > upper limit of normal [ULN]) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy; patients who are receiving denosumab must discontinue denosumab use and replace it with a bisphosphonate instead while on study; patients receiving a bisphosphonate for skeletal metastases are not excluded and can continue treatment
Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy;
Uncontrolled tumor-related pain, or uncontrolled hypercalcemia or clinically significant (symptomatic) hypercalcemia
Serum calcium (corrected for albumin) level at or below the ULN range (treatment of hypercalcemia is allowed and subject may enroll if hypercalcemia returns to normal with standard treatment) prior to study therapy initiation
Serum calcium (corrected for albumin) level at or below the ULN (treatment of hypercalcemia is allowed and participant may enroll if hypercalcemia returns to normal with standard treatment).
History of hypercalcemia
Uncontrolled or symptomatic hypercalcemia
Uncontrolled disease-related metabolic disorder (e.g., hypercalcemia);
Uncontrolled hypercalcemia
Hypercalcemia
Uncontrolled hypercalcemia
History of either symptomatic hypercalcemia or hyperparathyroidism, at the treating investigator’s discretion
Hypercalcemia
Serum calcium (corrected for albumin) level above the ULN range (treatment of hypercalcemia is allowed and subject may enroll if hypercalcemia returns to normal with standard treatment).
Uncontrolled hypercalcemia
< Grade 3 hypo/hypercalcemia
Uncontrolled hypercalcemia
Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab
Uncontrolled or symptomatic hypercalcemia
Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab General Medical Exclusion Criteria:
Uncontrolled or symptomatic hypercalcemia
History of hypercalcemia
History of clinically significant hypercalcemia
Uncontrolled hypercalcemia
Uncontrolled hypercalcemia
Symptomatic hypercalcemia
The patient has hypercalcemia.
The patient has hypercalcemia.
Uncontrolled hypercalcemia
Uncontrolled hypercalcemia
Subjects with hypercalcemia (> 10.5 mg/dL)
Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy
Subjects may be taking calcium supplements or have previous history of hypercalcemia
Known hypercalcemia
Uncontrolled or symptomatic hypercalcemia
Patients with hypercalcemia or kidney stones
Patients taking bisphosphonate therapy for symptomatic hypercalcemia; use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed
Patients taking bisphosphonate therapy for symptomatic hypercalcemia within the past 28 days; use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed
Patients taking bisphosphonate therapy for symptomatic hypercalcemia; use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed
Patients taking bisphosphonate therapy for symptomatic hypercalcemia are NOT allowed; use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed
Patients taking bisphosphonate therapy for symptomatic hypercalcemia; use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed
Patients taking bisphosphonate therapy for symptomatic hypercalcemia; use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed
GENERAL: Bisphosphonate therapy for symptomatic hypercalcemia\r\n* Use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed.
Patients taking bisphosphonate therapy for symptomatic hypercalcemia; use of bisphosphonate therapy for other reasons (e.g., osteoporosis) is allowed
Bisphosphonate therapy for symptomatic hypercalcemia. Use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed.
Bisphosphonate therapy for symptomatic hypercalcemia a) Use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed
Bisphosphonate therapy for symptomatic hypercalcemia\r\n* Use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed
Bisphosphonate therapy for symptomatic hypercalcemia\r\n* Use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed
Bisphosphonate therapy for symptomatic hypercalcemia\r\n* Use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed
Patients taking bisphosphonate therapy for symptomatic hypercalcemia\r\n* Note: use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed
Bisphosphonate therapy for symptomatic hypercalcemia (use of bisphosphonate therapy for other reasons [e.g., osteoporosis] is allowed.)
Bisphosphonate therapy for symptomatic hypercalcemia\r\n* Use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed
Patients taking bisphosphonate therapy for symptomatic hypercalcemia; use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed
Bisphosphonate therapy for symptomatic hypercalcemia\r\n* Use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed
Total calcium (corrected for serum albumin) within normal limits (ongoing requirement for bisphosphonate to control malignant hypercalcemia is not allowed but prophylactic use of bisphosphonate to prevent skeletal complication of bone metastasis is allowed)
Bisphosphonate therapy for symptomatic hypercalcemia\r\n* Use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed
Patients taking bisphosphonate therapy for symptomatic hypercalcemia; use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed
Bisphosphonate therapy for symptomatic hypercalcemia\r\n* Use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed
Patients taking bisphosphonate therapy for symptomatic hypercalcemia; use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed
Bisphosphonate therapy for symptomatic hypercalcemia
Bisphosphonate therapy for symptomatic hypercalcemia
Bisphosphonate therapy for symptomatic hypercalcemia
Bisphosphonate therapy for symptomatic hypercalcemia
Symptomatic hypercalcemia requiring continued use of bisphosphonate therapy
Symptomatic hypercalcemia requiring continued use of bisphosphonate therapy. Patients who are receiving bisphosphonate therapy specifically to prevent skeletal events and who do not have a history of clinically significant hypercalcemia are eligible.
Symptomatic hypercalcemia requiring continued use of bisphosphonate therapy
Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab (bisphosphonate use for prevention of skeletal events allowed)