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ACTRN12618001236280

Standard-Dose Combination Chemotherapy or High-Dose Combination Chemotherapy and Stem Cell Transplant in Treating Patients With Relapsed or Refractory Germ Cell Tumors

Data source: WHO (Imported from 20.03.2024)
Changed: Nov 17, 2019, 2:01 AM
Disease category:

Health conditions (Data source: WHO)

Germ Cell Tumor;Teratoma;Choriocarcinoma;Germinoma;Mixed Germ Cell Tumor;Yolk Sac Tumor;Childhood Teratoma;Malignant Germ Cell Neoplasm;Extragonadal Seminoma;Non-seminomatous Germ Cell Tumor;Seminoma;Cancer;
Germ Cell Tumor
Teratoma
Choriocarcinoma
Germinoma
Mixed Germ Cell Tumor
Yolk Sac Tumor
Childhood Teratoma
Malignant Germ Cell Neoplasm
Extragonadal Seminoma
Non-seminomatous Germ Cell Tumor
Seminoma
Cancer;Cancer - Testicular;Cancer - Other cancer types

Interventions (Data source: WHO)

Arm A: TIP

Arm A therapy will consist of 4 cycles of Paclitaxel, Ifosfamide, Cisplatin and Pegylated G-CSF administered every 21 days (+/- 4 days) as follows:

- Paclitaxel: 250 mg/m^2 IV over 24 hours on Day 1
*Premedication (refers to the minimum allowed but institutional protocols administering
additional or more intensive prophylaxis are allowed)
*Dexamethasone: 20 mg orally approximately 14 (12-24) hours and 7 (6-9) hours before
paclitaxel (taken by the patient at home the night before and morning of day 1 or 20 mg
IV 30-60 minutes prior to the initiation of the paclitaxel infusion.
*Diphenhydramine: 25 to 50 mg IVPB 30-60 minutes prior to paclitaxel. Oral can be
substituted but must be given 60 minutes prior to paclitaxel. An equivalent H1 blocker
(e.g., hydroxyzine) can be substituted for diphenhydramine.
*H2 blocker: Ranitidine, Cimetidine, and Famotidine are acceptable, given orally 60
minutes prior or by IVPB 30-60 minutes prior to paclitaxel.

- Ifosfamide: 1500 mg/m^2 IV daily on Days 2-5 with mesna protection
*Mesna: 1500 mg/^2 should be given to match the ifosfamide dose, either mixed 1:1 with
ifosfamide or simultaneous in a separate bag or pre- or post- ifosfamide and hydration.

- Cisplatin 25 mg/m^2 IV daily on Days 2-5

- Pegylated Granulocyte Colony Stimulating Factor (G-CSF) 6 mg subcutaneous on Day 6, 7
or 8 (as determined by the investigator).

- Hydration guidelines: At least one liter of normal saline prior to the initiation of cisplatin.
Hydration should consist of normal saline infused at 100 mL/hr and continue throughout the 5 days of chemotherapy. At least one liter of normal saline should be given post the last dose of cisplatin. Hydration can be modified per institutional guidelines.

- Prophylactic fluoroquinolone antibiotics: Levofloxacin 500mg once daily by mouth or
Ciprofloxacin 500mg twice daily by

Inclusion/Exclusion Criteria (Data source: WHO)

Inclusion criteria: 1. Documentation of Disease

- Histologic Documentation: Confirmation of GCT histology (both seminoma and nonseminoma) on pathologic review at the center of enrollment.
- Tumor may have originated in any primary site. NOTE: In rare circumstances, patients will be allowed to enroll even if a pathological diagnosis may not have been established.
- This would require a clinical situation consistent with the diagnosis of GCT (testicular, peritoneal, retroperitoneal or mediastinal mass, elevated tumor marker levels {HCG greater than or equal to 500; AFP greater than or equal to 500} and typical pattern of metastases)

2. Evidence of Disease

- Must have evidence of progressive or recurrent GCT (measurable or non-measurable) following one line of cisplatin-based chemotherapy, defined as meeting at least one of the following criteria:

* Tumor biopsy of new or growing or unresectable lesions demonstrating viable non-teratomatous GCT (enrollment on this study for adjuvant treatment after macroscopically complete resection of viable GCT is not allowed). In the event of an incomplete gross resection where viable GCT is found, patients will be considered eligible for the study.
* Consecutive elevated serum tumor markers (HCG or AFP) that are increasing. Increase of an elevated LDH alone does not constitute progressive disease.
* Development of new or enlarging lesions in the setting of persistently elevated HCG or AFP, even if the HCG and AFP are not continuing to increase.

3. Prior Treatment

- Must have received 3-6 cycles of cisplatin-based chemotherapy as part of first-line (initial) chemotherapy.

* Prior POMBACE, CBOP-BEP, or GAMEC are allowed.
* Note: For patients requiring immediate treatment, 1 cycle of conventional-dose salvage chemotherapy is allowed. Therefore, these patients may have received 7 prior cycles of chemotherapy. 6 cycles as part of first-line chemotherapy and 1 cycle of salvage conventional chemotherapy.

- No more than one prior line of chemotherapy for GCT (other than the 1 cycle of salvage chemotherapy)

* Definition of one line of chemotherapy: One line of therapy can in some cases consist of 2 different cisplatin-based treatment combinations, provided there is no disease progression between these two regimens.
* Prior treatment with carboplatin as adjuvant therapy is allowed, provided patients meet other eligibility criteria (e.g., the patient has also received 3-4 cycles of cisplatin-based chemotherapy).
* Prior treatment with 1-2 cycles of BEP or EP as adjuvant chemotherapy for early stage GCT is allowed, provided the patient also received 3-4 cycles of BEP or EP again at relapse. Patients treated with 3-4 cycles of VIP at relapse following 1-2 cycles of BEP/EP are not eligible as this would be considered more than 1 line of prior therapy.

- No prior treatment with high-dose chemotherapy (defined as treatment utilizing stem cell rescue)
- No prior treatment with TIP with the exception when given as a bridge to treatment on protocol for patients with rapidly progressive disease who cannot wait to complete the eligibility screening process. Only one cycle is allowed.
- No concurrent treatment with other cytotoxic drugs or targeted therapies.
No radiation therapy (other than to the brain) within 14 days of day 1 of protocol chemotherapy except radiation to brain metastases, which must be completed 7 days prior to start of chemotherapy.
- No previous chemotherapy within 17 days prior to
Exclusion criteria: 1. Prior treatment with high-dose chemotherapy
2. Prior treatment with TIP
*1 cycle of Prior TIP is allowed as bridge to the protocol
3. Prior radiation within 14 days
4. Prior chemotherapy within 16 days (bleomycin within 5 days)
5. Inadequate recovery from prior surgery
6. Concurrent malignancy
7. Large hemorrhagic or symptomatic brain metastases
*Become eligible 7 days or more after local treatment (surgery or RT)
8. Fully resectable late relapse (2 years or more before relapse)
9. Concurrent malignancy

Further information on the trial in WHO primary registry

https://anzctr.org.au/ACTRN12618001236280.aspx

Further information on the trial from WHO database (ICTRP)

https://trialsearch.who.int/Trial2.aspx?TrialID=ACTRN12618001236280
Further information on trial

Date trial registered

Jul 23, 2018

Incorporation of the first participant

Sep 28, 2018

Recruitment status

Recruiting

Academic title (Data source: WHO)

A Randomized Phase III Trial Comparing Conventional-Dose Chemotherapy Using Paclitaxel, Ifosfamide, and Cisplatin (TIP) With High-Dose Chemotherapy Using Mobilizing Paclitaxel Plus Ifosfamide Followed by High-Dose Carboplatin and Etoposide (TI-CE) as First Salvage Treatment in Relapsed or Refractory Germ Cell Tumors

Type of trial (Data source: WHO)

Interventional

Design of the trial (Data source: WHO)

Purpose: Treatment; Allocation: Randomised controlled trial; Masking: Open (masking not used);Assignment: Parallel;Type of endpoint: Safety/efficacy

Phase (Data source: WHO)

Phase 3

Primary end point (Data source: WHO)

Overall survival[Overall survival will be defined from date of randomisation to death due to any cause. For surviving patients, overall survival will be censored on the date the patient was last know to be alive as assessed at 3 years post treatment commencement.]

Secundary end point (Data source: WHO)

To prospectively evaluate the IPFSG scoring system as a predictor of outcome to initial salvage therapy in patients with relapsed or refractory GCT. In this trial, randomisation will be stratified by a modification of the IPFSG category and we will prospectively evaluate whether or not actual outcomes vary by risk group in the appropriate manner (low risk patients have higher OS than high-risk group). [3 years post-registration];Toxicity[Toxicities will be evaluated and recorded based on the NCI common toxicity criteria (CTCAE v4.0). They will be described by frequency and grade, by cycle and over all cycles, with the maximum grade over all cycles used as the summary measure for each patient.];Treatment related mortality[Treatment-related mortality: Treatment-related mortality will be defined as any death
occurring during protocol chemotherapy, or within 30-days following the end of this
treatment.];Favorable Response Rate[Favorable Response Rate (FRR): The favorable response rate (FRR) will be defined as the
proportion of patients achieving either a complete response (CR) or partial response with
normal serum tumor markers (PR-neg) at the time of the end of treatment assessment (Arm A: less than or equal to 28 days from last day of cisplatin; Arm B: less than or equal to 28 days from the last stem cell re-infusion). ];Progression free survival (PFS).
PFS will be measured via medical records kept at the hospital where the patient was treated. [Progression Free Survival: PFS will be measured from the date of randomization to date of
progression or death due to any cause, whichever occurs first.]

Contact information (Data source: WHO)

Australian and New Zealand Urogenital and Prostate Cancer Trials (ANZUP)

Trial results (Data source: WHO)

Results summary

no information available yet

Link to the results in the primary register

no information available yet

Information on the availability of individual participant data

no information available yet

Trial sites

Countries (Data source: WHO)

Australia, Belgium, Denmark, France, Germany, Ireland, Italy, Netherlands, Spain, Switzerland, United Kingdom, United States of America

Further trial identification numbers

Secondary ID (Data source: WHO)

ClinicalTrials.gov: NCT02375204
Alliance for Clinical Trials in Oncology: A031102
NCI-2014-01696 (Registry Identifier: NCI Clinical Trial Reporting Program)
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