CLINICAL TRIAL / NCT01873326
Paclitaxel, Ifosfamide and Cisplatin (TIP) Versus Bleomycin, Etoposide and Cisplatin (BEP) for Patients With Previously Untreated Intermediate- and Poor-risk Germ Cell Tumors
- Interventional
- Active
- NCT01873326
Contact Information
Randomized Phase II Trial of Paclitaxel, Ifosfamide and Cisplatin (TIP) Versus Bleomycin, Etoposide and Cisplatin (BEP) for Patients With Previously Untreated Intermediate- and Poor-Risk Germ Cell Tumors
The purpose of this study is to learn about the safety and effectiveness of two different drug combinations in patients who have intermediate- and poor-risk germ cell tumors (GCT). One combination of drugs, paclitaxel, ifosfamide and cisplatin (TIP), is experimental. The other combination of drugs, bleomycin, etoposide and cisplatin (BEP), is the standard of care treatment for intermediate- and poor-risk germ cell tumors. However, BEP does not cure every patient and therefore newer treatments are needed.
Gender
All
Age Group
18 Years and up
Accepting Healthy Volunteers
No
Inclusion Criteria:
- Patients ≥ 18 years of age.
- Patients with newly diagnosed GCT
- Pathology confirmation of GCT histology at MSKCC or a collaborating treating
institution. In exceptional circumstances, patients without pathological diagnosis
may be included in the study following discussion with the national principal
investigator, Dr. Feldman,(or national Co-PI or MSKCC Co-PI if the national PI is
unavailable) if they meet the one of the following criteria:
- Patients with a testicular mass (detected clinically and/or by ultrasound), and/or
mediastinal or retroperitoneal lymphadenopathy or pineal tumor AND elevated serum
tumor markers (HCG and/or AFP). Patients with elevated LDH only will not be included
without pathological confirmation of GCT since LDH is a nonspecific marker for GCT
and could potentially be elevated in other malignancies such as lymphomas.
This is because patients may present with a clinical scenario consistent with GCT
(elevated serum tumor markers, testicular mass and retroperitoneal lymphadenopathy) with
a concurrent life-threatening oncologic emergency that require immediate treatment. In
this case, initial treatment without biopsy confirmation is usually recommended and
tissue confirmation may be obtained after initiating therapy.
- Patients must have measurable or evaluable disease.
- Patients must be classified as having intermediate or poor-risk germ cell tumor, as
follows:
- Intermediate-risk (Modified*) a) Testis or retroperitoneal primary NSGCT with
lymph node and/or lung metastasis but without non-pulmonary visceral metastasis
AND any of the following pretreatment serum tumor marker (STM) values: i.
Lactate dehydrogenase (LDH) from 3 to <10 x ULN (*This differs from the
original IGCCCG criteria which includes patients with LDH from 1.5 to 10 x
ULN).
ii. Serum human chorionic gonadotrophin (HCG) from 5,000 to < 50,000 MIU/mL iii. Serum
alpha-fetoprotein (AFP) from 1,000 to <10,000 ng/mL b) Seminoma histology regardless the
primary site or serum tumor markers with any non-pulmonary visceral metastasis (liver,
bone, brain, etc).
- Poor-risk (any of the following):
1. Testis or retroperitoneal NSGCT primary with non-pulmonary visceral metastasis
(liver, bone, brain, etc) regardless the STM values.
2. Mediastinal NSGCT primary site of disease regardless the presence/absence of
visceral metastasis or STM values.
3. Testis or retroperitoneal NSGCT primary without non-pulmonary visceral
metastasis but with poor-risk STM values:
- i. LDH ≥ 10 x ULN
- ii. HCG ≥ 50,000 MIU/mL
- iii. AFP ≥ 10,000 ng/mL
- Patients who received prior radiation therapy (RT) for treatment of germ cell
tumor are eligible for this study as long as there is evidence of progressive
disease determined by tumor markers or other sites of metastases outside of the
radiated site. Radiation must be completed prior to starting chemotherapy with
the exception of brain metastases where chemotherapy and radiation can be given
concurrently. Toxicity from radiation must have recovered to grade 1 or less
prior to initiating chemotherapy.
- Patients must have recovered from prior surgery based on treating physician's
discretion.
- Patients of reproductive potential must agree to use effective contraception
during the period of therapy
- Signed informed consent.
- Diffusion lung capacity for carbon monoxide (DLCO) adjusted for hemoglobin ≥60%
predicted, except if related to high volume metastatic GCT to the lungs in
which case there is no minimum DLCO requirement. In some cases, patients may
not be able to undergo PFT testing due to the severity of their presentation.
such as those with high volume lung metastases or tumor-related pain (from
large mediastinal masses, pleural disease, etc.) limiting their ability to
complete PFTs. Even when PFTs can be completed in these cases, patients will
still be eligible if the low DLCO can be attributed directly to the patient's
disease (e.g., large mediastinal mass) rather than intrinsic lung disease.
Since there is no minimum DLCO for these patients, under these extraordinary
circumstances, this will be allowed. Most patients in this situation will be
expected to receive disease-stabilizing chemotherapy. An unadjusted DLCO may be
used in place of the DLCO adjusted for hemoglobin in certain situations as per
institutional policy. For example, MSKCC policy is to not adjust the DLCO for
hemoglobin when the hemoglobin is ≥ 14.6 g/dL for males and ≥ 13.4 g/dL for
females. In these cases, the unadjusted DLCO must be >60% predicted.
- Laboratory criteria for protocol entry (obtained ≤ 14 days before initiation of
therapy):
- WBC ≥ 3000/UL and Platelet count ≥ 100,000/UL
- Serum creatinine ≤ 1.5 mg/dL or estimated GFR (by Cockcroft-Gault) ≥50mL/min or 12
or 24 hour urine creatinine clearance ≥ 50 mL/min, unless renal insufficiency is due
to tumoral ureteral obstruction in which case eligibility will be determined by
national the principal investigator (or national co-PI or MSKCC co-PI if the
national PI is unavailable) with notification of the MSKCC IRB.
- AST/ALT ≤ 3 x ULN and total bilirubin ≤ 2.0 x ULN. In the setting of metastatic
disease to the liver, AST/ALT may be ≤5x ULN and total bilirubin ≤2.5 x ULN. If a
patient is known or suspected to have Gilbert's disease, total bilirubin up to ≤2.5
x ULN is allowed.
Exclusion Criteria:
- Any prior chemotherapy. The only exception will be patients with a history of stage
I seminoma treated with adjuvant carboplatin for 1 or 2 cycles.
- Concurrent treatment with any cytotoxic therapy.
- Known concurrent malignancy (except for non-melanoma skin cancer).
- Patients known to be HIV positive and receiving HAART.
- Presence of an active infection. Patients with fever assessed to be "tumor fever"
but without active evidence of infection (e.g. blood cultures are negative) are
eligible. In addition, patients who have an infection but without evidence of fever
for 48 hours on antibiotics will be eligible.
- Inability to comply with the treatment protocol or to undergo prespecified follow-up
tests for safety or effectiveness.
- Pregnant patients are ineligible